MXPA01000432A - Compositions and methods for therapy and diagnosis of prostate cancer - Google Patents
Compositions and methods for therapy and diagnosis of prostate cancerInfo
- Publication number
- MXPA01000432A MXPA01000432A MXPA/A/2001/000432A MXPA01000432A MXPA01000432A MX PA01000432 A MXPA01000432 A MX PA01000432A MX PA01000432 A MXPA01000432 A MX PA01000432A MX PA01000432 A MXPA01000432 A MX PA01000432A
- Authority
- MX
- Mexico
- Prior art keywords
- seq
- patient
- polypeptide
- polynucleotide
- cdna sequence
- Prior art date
Links
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Abstract
Compositions and methods for the therapy and diagnosis of cancer, such as prostate cancer, are disclosed. Compositions may comprise one or more prostate tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a prostate tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as prostate cancer. Diagnostic methods based on detecting a prostate tumor protein, or mRNA encoding such a protein, in a sample are also provided.
Description
COMPOSITIONS AND METHODS FOR THERAPY AND DIAGNOSIS OF PROSTATE CANCER
TECHNICAL FIELD The present invention relates generally to cancer therapy and diagnosis, such as, prostate cancer. The invention relates more specifically to polypeptides comprising at least a portion of prostate tumor protein, and to polynucleotides encoding such polypeptides. Such polypeptides and polynucleotides can be used in vaccines and pharmaceutical compositions for the prevention and treatment of prostate cancer, and for the diagnosis and monitoring of such cancers.
BACKGROUND OF THE INVENTION Prostate cancer is the most common form of cancer among men, with an estimated incidence of 30% in men above the age of 50 years. Overwhelming clinical evidence shows that human prostate cancer has a propensity to spread to bone, and the disease appears to inevitably progress from androgen dependent on the androgen refractory state, leading to increased patient mortality. This frequent disease is currently the second cause that leads to cancer bites among men in the United States.
Despite considerable research on therapies for the disease, prostate cancer remains difficult to treat. Usually, the treatment is based on surgery and / or radiation therapy, but these methods are ineffective in a significant percentage of cases. Two specific prostate proteins identified - prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) - have limited therapeutic and diagnostic potential. For example, PSA levels do not always correlate well with the presence of prostate cancer, being positive in a percentage of non-prostate cancer cases, including benign prostatic hyperplasia (BPH). Additionally, PSA measurements correlate with prostate volume, and do not indicate the level of metastasis. Despite considerable research on therapies for these and other cancers, prostate cancer remains difficult to diagnose and treat effectively. Accordingly, there is a need in the art for improved methods to detect and treat such cancers. The present invention meets these needs and further provides other related advantages.
BRIEF DESCRIPTION OF THE INVENTION As briefly stated, the present invention provides numerous positions and methods for the diagnosis and therapy of cancer, such as prostate cancer. In one aspect, the present invention provides polypeptides comprising at least a portion of a prostate tumor protein, or a variant thereof. Certain portions and other variants are immunogenic, so that the ability of the variant to react with antigen-specific antiserum is not substantially diminished. Within certain embodiments, the polypeptide comprises at least an immunogenic portion of a prostate tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consists of: (a) sequences declared in any of SEQ ID Nos: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340- 375, 381, 382 or 384-472; b) sequences that hybridize to any of the above sequences under moderately severe conditions; and (c) complements of any of the sequence of (a) or (b). In certain specific modalities, such a polypeptide comprises at least a portion, or variant thereof, of a tumor protein that includes an amino acid sequence selected from the group consisting of sequences declared in any of SEQ ID NO: 112-114, 172 , 176, 178, 327, 329, 331, 336, 339, 376-380 and 383. The present invention further provides polynucleotides that encode a polypeptide as described herein, or a portion thereof (such portion encoding at least 15 amino acid residues of a prostate tumor protein), expression vectors comprising such polynucleotides and host cells transformed or transfected with such expression vectors. Within other aspects, the present invention provides pharmaceutical compositions comprising a polypeptide or polynucleotide as described above and a physiologically acceptable carrier. Vaccines are provided within a related aspect of the present invention. Such vaccines comprise a polypeptide or polynucleotide, as described above and a non-specific immune response enhancer. The present invention further provides pharmaceutical compositions comprising: (a) an antibody or antigen-binding fragment thereof, which specifically binds to a prostate tumor protein; and (b) a physiologically acceptable carrier. Within additional aspects, the present invention provides pharmaceutical compositions comprising: (a) an antigen-presenting cell that expresses a polypeptide as described above, and (b) a pharmaceutically acceptable carrier or excipient. Antigen presenting cells include dendritic cells, macrophages, monocytes, fibroblasts, and B cells. Related aspects include vaccines comprising: (a) an antigen-presenting cell that expresses a polypeptide as described above, and (b) a non-specific immune response enhancer.
The present invention further provides, in other aspects, fusion proteins comprising at least one polypeptide as described above, as well as polynucleotides that encode such fusion proteins. Within related aspects, pharmaceutical compositions comprising a fusion protein, or a polynucleotide encoding a fusion protein, in combination with a physiologically acceptable carrier are provided. Vaccines are also provided, within other aspects, comprising a fusion protein, or a polynucleotide which
• encodes a fusion protein, in combination with a non-specific immune response enhancer. Within additional aspects, the present invention provides methods for inhibiting the development of a cancer in a patient, which comprises administering to a patient a pharmaceutical composition or vaccine as stated above. The present invention also provides, within other aspects, methods for removing tumor cells from a sample
• biological, which comprises contacting a biological sample with 20 T cells that specifically react with a prostate tumor protein, wherein the contact step is carried out under conditions and for a sufficient time to allow the removal of the expressing cells the protein of the sample. Within related aspects, the methods are provided to inhibit the development of a cancer in a patient, comprising administering to a patient a biological sample treated as described above. The methods are further provided, within other aspects, for stimulating and / or expanding specific T cells for a prostate tumor protein, comprising contacting T cells with one or more of: (i) a polypeptide as described above; (ii) a polynucleotide encoding such a polypeptide; and / or (iii) an antigen-presenting cell expressing such a polypeptide; under conditions and for a time sufficient to allow the stimulation and / or expansion of T cells. Isolated T cell populations comprising T cells prepared as described above are also provided. Within additional aspects, the present invention provides methods for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a population of T cells as described above. The present invention further provides methods for inhibiting the development of a cancer in a patient, comprising the steps of: (a) incubating CD4 + and / or CD8 + T cells isolated from a patient with one or more of: (i) a polypeptide that comprises at least one immunogenic portion of a prostate tumor protein; (ii) a polynucleotide encoding such a polypeptide; and (m) an antigen presenting cell expressing such a polypeptide; and (b) administering to the patient an effective amount of the proliferated T cells, and thereby inhibiting the development of a cancer in the patient. Proliferated cells may be, but not necessarily, cloned before administration to the patient. Within additional aspects, the present invention provides methods for determining the presence or absence of a cancer in a patient, comprising: (a) contacting a biological sample obtained from a patient with a binding agent that binds to a polypeptide as declare before; (b) detecting in the sample, an amount of polypeptide that binds to the binding agent; and (c) comparing the amount of polypeptide with a cut-off value
predetermined, and determine from there the presence or
• absence of cancer in the patient. Within preferred embodiments, the binding agent is an antibody, more preferably a monoclonal antibody. The cancer can be prostate cancer. The present invention also provides, within other aspects, methods for monitoring the progression of a cancer in a patient. Such methods comprise the steps of: (a) contacting a biological sample obtained from a patient at a first point
• in time with a binding agent that binds to a polypeptide
as stated before; (b) detecting in the sample an amount of polypeptide that binds to the binding agent; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and (d) comparing the amount of polypeptide detected in step (c) with the amount detected in step (b) and thence monitoring the progression of the cancer in the patient. The present invention further provides, within other aspects, methods for determining the presence or absence of a cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes a prostate tumor protein; (b) detecting in the sample, a level of a polynucleotide, preferably mRNA, that hybridizes to the oligonucleotide; and (c) comparing the level of polynucleotide that hybridizes to the oligonucleotide with a predetermined cut-off value, and thence determining the presence or absence of a cancer in the patient. Within certain embodiments, the amount of mRNA is detected via the polymerase chain reaction using, for example, at least one oligonucleotide primer that hybridizes to a polynucleotide that encodes a polypeptide as stated above, or a complement to such a polynucleotide. Within other embodiments, the amount of mRNA is detected using a hybridization technique, employing an oligonucleotide probe that hybridizes to a polynucleotide that encodes a polypeptide as stated above, or a complement to such a polynucleotide. In related aspects, the methods are provided to monitor the progression of a cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes a tumor prostate; (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and (d) comparing the amount of polynucleotide detected in step (c) with the amount detected in step (b) and thence monitoring the progression of the cancer in a patient. Within additional aspects, the present invention provides antibodies, such as monoclonal antibodies, that bind to a polypeptide as described above, as well as diagnostic kits comprising such antibodies. Diagnostic sets comprising one or more probes or oligonucleotide primers as described above are also provided. These and other aspects of the present invention will become apparent upon reference to the following detailed description and appended drawings. All references described herein are incorporated by reference in their entirety, as if each were incorporated individually.
BRIEF DESCRIPTION OF THE SEQUENCE DRAWINGS AND IDENTIFIERS Figure 1 illustrates the ability of T cells to kill fibroblasts expressing the representative prostate tumor polypeptide P502S, as compared to control fibroblasts.
The percentage of lysis is shown as a series of effector: objective proportions, as indicated. Figures 2A and 2B illustrate the ability of T cells to recognize cells expressing the representative prostate tumor polypeptide P502S. In each case, the number of? -interferon spots for different numbers of responders is shown. In Figure 2A, data are presented for pulsed fibroblasts with the P2S-12 peptide, as compared to pulsed fibroblasts with an E75 control peptide. In Figure 2, data 10 presents data for fibroblasts expressing P502S, as compared to fibroblasts expressing HER-2 / neu. Figure 3 depicts a peptide competition binding assay showing that the peptide PlS # 10, derivative of P501S, binds to HLA-A2. Peptide P1S # 10 inhibits the restricted presentation of HLA-A2 of the fluM58 peptide in the CTL clone D150M58 in the TNF release bioassay. D150M58 CTL is specific for the influenza matrix fluM58 peptide that binds to HLA-A2. Figure 4 illustrates the ability of T f cell lines generated from mice immunized with P1S # 10 to specifically use Jurkat A2Kb targets pulsed with P1S # 10 and Jurkat A2Kb targets transduced with P501S, as compared to transduced Jurkat A2Kb with EGFP. The percentage of lysis is shown as a series of effector to objective propotions, as indicated.
Figure 5 illustrates the ability of a T cell clone to specifically recognize and lyse Jurkat A2Kb cells expressing the representative prostate tumor polypeptide P501S, thereby demonstrating that the peptide PlS # 10 can be a naturally processed epitope of the polypeptide P501S. Figures 6A and 6B are graphs illustrating the specificity of a CD8 + cell line (3A-1) for a representative prostate tumor antigen (P501S). Figure 6A shows the results of a 51Cr release assay. The percentage of specific lysis is shown as a series of effector: target ratios, as indicated. Figure 6B shows the production of interferon-gamma by 3A-1 cells stimulated with autologous B-LCL transduced with P501S, in varying proportions of effector: target, as indicated. SEQ ID NO: 1 is the cDNA sequence determined for Fl-13 SEQ ID NO: 2 is the 3 'cDNA sequence determined for Fl-12 SEQ ID NO: 3 is the 5' cDNA sequence determined for Fl-12 SEQ ID NO: 4 is the 3 'cDNA sequence determined for Fl-16 SEQ ID NO: 5 is the 3' cDNA sequence determined for Hl-1 SEQ ID NO: 6 is the 3 'cDNA sequence determined for Hl-9 SEQ ID NO: 7 is the 3 'cDNA sequence determined for Hl-4 SEQ ID NO: 8 is the 3' cDNA sequence determined for Jl-17 SEQ ID NO: 9 is the 5 'cDNA sequence determined for Jl- 17 SEQ ID NO: 10 is the 3 'cDNA sequence determined for Ll-12 SEQ ID NO: 11 is the 5' cDNA sequence determined for Ll-12 SEQ ID NO: 12 is the cDNA 3 sequence determined for Nl- -1862
SEQ ID NO: 13 is the sequence of cDNA 5 determined for Nl-1862
SEQ ID NO: 14 is the sequence of cDNA 3 determined for Jl-13 SEQ ID NO: 15 is the sequence of cDNA 5 determined for Jl-13
F SEQ ID NO: 16 is the sequence of cDNA 3 determined for Jl-19 SEQ ID NO: 17 is the sequence of cDNA 5 determined for Jl-19 SEQ ID NO: 18 is the sequence of cDNA 3 determined for Jl- -25 SEQ ID NO: 19 is the sequence of cDNA 5 determined for Jl-25 SEQ ID NO: 20 is the sequence of cDNA 5 determined for Jl-24 SEQ ID NO: 21 is the sequence of cDNA 3 determined for Jl --24
F SEQ ID NO: 22 is the sequence of cDNA 5 determined for Kl-58 SEQ ID NO: 23 is the sequence of cDNA 3 determined for Kl-58 SEQ ID NO: 24 is the sequence of cDNA 5 determined for Kl- -63 SEQ ID NO: 25 is the sequence of cDNA 3 determined for Kl-63 15 SEQ ID NO: 26 is the sequence of cDNA 5 determined for Ll-4 SEQ ID NO: 27 is the sequence of cDNA 3 determined for Ll-4 SEQ ID NO: 28 is the sequence of cDNA 5 determined for Ll-14 SEQ ID NO: 29 is the sequence of cDNA 3 determined for Ll-14
F SEQ ID NO: 30 is the sequence of cDNA 3 determined for Jl-12 SEQ ID NO: 31 is the sequence of cDNA 3 determined for Jl-16 SEQ ID NO: 32 is the sequence of cDNA 3 determined for Jl - 21 SEQ ID NO: 33 is the sequence of cDNA 3 determined for Kl-48 SEQ ID NO: 34 is the sequence of cDNA 3 determined for Kl-55
SEQ ID NO: 35 is the sequence of cDNA 3 determined for Ll-2 SEQ ID NO: 36 is the sequence of cDNA 3 determined for Ll-6 SEQ ID NO: 37 is the sequence of cDNA 3 'determined for Nl -1858
SEQ ID NO: 38 is the 3 'cDNA sequence determined for Nl-1860
SEQ ID NO: 39 is the 3 'cDNA sequence determined for Nl-1861 f SEQ ID NO: 40 is the 3' cDNA sequence determined for Nl-1864
SEQ ID NO: 41 is the cDNA sequence determined for P5 SEQ ID NO: 42 is the cDNA sequence determined for P8 SEQ ID NO: 43 is the cDNA sequence determined for P9 SEQ ID NO: 44 is the cDNA sequence determined for P18 SEQ ID NO: 45 is the cDNA sequence determined for P20 10 SEQ ID NO: 46 is the cDNA sequence determined for P29 f SEQ ID NO: 47 is the cDNA sequence determined for P30 SEQ ID NO: 48 is the cDNA sequence determined for P34 SEQ ID NO: 49 is the cDNA sequence determined for P36 SEQ ID NO: 50 is the cDNA sequence determined for P38 SEQ ID NO: 51 is the cDNA sequence determined for P39 SEQ ID NO: 52 is the cDNA sequence determined for P42 SEQ ID NO: 53 is the cDNA sequence determined for P47 SEQ ID NO: 54 is the cDNA sequence determined for P49 SEQ ID NO: 55 is the cDNA sequence determined for P50 20 SEQ ID NO: 56 is the cDNA sequence determined for P53 SEQ ID NO: 57 is the sequence of cDNA determined for P55 SEQ ID NO: 58 is the cDNA sequence determined for P60 SEQ ID NO: 59 is the cDNA sequence determined for P64 SEQ ID NO: 60 is the cDNA sequence determined for P65 25 SEQ ID NO: 61 is the cDNA sequence determined for P73 SEQ ID NO: 62 is the cDNA sequence determined for P75
SEQ ID NO: 63 is the cDNA sequence determined for P76
SEQ ID NO: 64 is the cDNA sequence determined for P79
SEQ ID NO: 65 is the cDNA sequence determined for P84 SEQ ID NO: 66 is the cDNA sequence determined for P68
SEQ ID NO: 67 is the cDNA sequence determined for P80
SEQ ID NO: 68 is the cDNA sequence determined for P82
SEQ ID NO: 69 is the cDNA sequence determined for Ul-3064
SEQ ID NO: 70 is the cDNA sequence determined for Ul-3065 SEQ ID NO: 71 is the cDNA sequence determined for Vl-3692
SEQ ID NO: 72 is the cDNA sequence determined for 1A-3905
SEQ ID NO: 73 is the cDNA sequence determined for Vl-3686
SEQ ID NO: 74 is the cDNA sequence determined for Rl-2330
SEQ ID NO: 75 is the cDNA sequence determined for 1B-3976 SEQ ID NO: 76 is the cDNA sequence determined for Vl-3679
SEQ ID NO: 77 is the cDNA sequence determined for 1G-4736
SEQ ID NO: 78 is the cDNA sequence determined for 1G-4738
SEQ ID NO: 79 is the cDNA sequence determined for 1G-4741
SEQ ID NO: 80 is the cDNA sequence determined for 1G-4744 SEQ ID NO: 81 is the cDNA sequence determined for 1G-4734
SEQ ID NO: 82 is the cDNA sequence determined for 1H-4774
SEQ ID NO: 83 is the cDNA sequence determined for 1H-4781
SEQ ID NO: 84 is the cDNA sequence determined for 1H-4785
SEQ ID NO: 85 is the cDNA sequence determined for 1H-4787 SEQ ID NO: 86 is the sequence of cDN1z determined for 1H-4796 SEQ ID NO: 87 is the cDNA sequence determined for 11-4807
SEQ ID NO: 88 is the cDNA sequence determined for 11-4810
SEQ ID NO: 89 is the cDNA sequence determined for 11-4811
SEQ ID NO: 90 is the cDNA sequence determined for 1J-4876
SEQ ID NO: 91 is the cDNA sequence determined for 1K-4884
SEQ ID NO: 92 is the cDNA sequence determined for 1K-4896
SEQ ID NO: 93 is the cDNA sequence determined for 1G-4761
SEQ ID NO: 94 is the cDNA sequence determined for 1G-4762
SEQ ID NO: 95 is the cDNA sequence determined for 1H-4766
SEQ ID NO: 96 is the cDNA sequence determined for 1H-4770
SEQ ID NO: 97 is the cDNA sequence determined for 1H-4771
SEQ ID NO: 98 is the cDNA sequence determined for 1H-4772
SEQ ID NO: 99 is the cDNA sequence determined for 1D-4297
SEQ ID NO: 100 is the cDNA sequence determined for 1D-4309
SEQ ID NO: 101 is the cDNA sequence determined for ID.1-4278
SEQ ID NO: 102 is the cDNA sequence determined for 1D-4288
SEQ ID NO: 103 is the cDNA sequence determined for 1D-4283
SEQ ID NO: 104 is the cDNA sequence determined for 1D-4304
SEQ ID NO: 105 is the cDNA sequence determined for 1D-4296
SEQ ID NO: 106 is the cDNA sequence determined for 1D-4280
SEQ ID NO: 107 is the full-length cDNA sequence, determined for Fl-12 (also referred to as P504S) SEQ ID NO: 108 is the predicted amino acid sequence for Fl-12
SEQ ID NO: 109 is the full length cDNA sequence determined for Jl-17 SEQ ID NO: 110 is the cDNA sequence determined for Ll-12 SEQ ID NO: 111 is the cDNA sequence determined for Nl-1862 SEQ ID NO: 112 is the amino acid sequence predicted for Jl-17
SEQ ID NO: 113 is the predicted amino acid sequence for Ll-12 5 SEQ ID NO: 114 is the predicted amino acid sequence for Nl-1862 SEQ ID NO: 115 is the cDNA sequence determined for P89 SEQ ID NO: 116 is the cDNA sequence determined for P90 SEQ ID NO: 117 is the cDNA sequence determined for P92 10 SEQ ID NO: 118 is the cDNA sequence determined for P95 F SEQ ID NO: 119 is the cDNA sequence determined for P98 SEQ ID NO: 120 is the cDNA sequence determined for P102 SEQ ID NO: 121 is the cDNA sequence determined for P110 SEQ ID NO: 122 is the cDNA sequence determined for Pili 15 SEQ ID NO: 123 is the cDNA sequence determined for P114 SEQ ID NO: 124 is the cDNA sequence determined for P115 SEQ ID NO: 125 is the cDNA sequence determined for P116 SEQ ID NO: 126 is the cDNA sequence determined for P124 SEQ ID NO: 127 is the determined cDNA sequence for P126 SEQ ID NO: 128 is the cDNA sequence determined for P130 SEQ ID NO: 129 is the cDNA sequence determined for P133 SEQ ID NO: 130 is the cDNA sequence determined for P138 SEQ ID NO: 131 is the sequence of cDNA determined for P143 SEQ I? MO: 132 is the cDNA sequence determined for P151 SEQ ID NO: 133 is the cDNA sequence determined for P156 SEQ ID NO: 134 is the cDNA sequence determined for P157
SEQ ID NO: 135 is the cDNA sequence determined for P166
SEQ ID NO: 136 is the cDNA sequence determined for P176 f SEQ ID NO: 137 is the cDNA sequence determined for P178
SEQ ID NO: 138 is the cDNA sequence determined for P179
SEQ ID NO: 139 is the cDNA sequence determined for P185
SEQ ID NO: 140 is the cDNA sequence determined for P192
SEQ ID NO: 141 is the cDNA sequence determined for P201
SEQ ID NO: 142 is the cDNA sequence determined for P204
SEQ ID NO: 143 is the cDNA sequence determined for P208 f SEQ ID NO: 144 is the cDNA sequence determined for P211
SEQ ID NO: 145 is the cDNA sequence determined for P213
SEQ ID NO: 146 is the cDNA sequence determined for P219
SEQ ID NO: 147 is the cDNA sequence determined for P237
SEQ ID NO: 148 is the cDNA sequence determined for P239
SEQ ID NO: 149 is the cDNA sequence determined for P248
SEQ ID NO: 150 is the cDNA sequence determined for P251
SEQ ID NO: 151 is the cDNA sequence determined for P255
SEQ ID NO: 152 is the cDNA sequence determined for P256
SEQ ID NO: 153 is the cDNA sequence determined for P259
SEQ ID NO: 154 is the cDNA sequence determined for P260
SEQ ID NO: 155 is the cDNA sequence determined for P263
SEQ ID NO: 156 is the cDNA sequence determined for P264
SEQ ID NO: 157 is the cDNA sequence determined for P266
SEQ ID NO: 158 is the cDNA sequence determined for P270 SEQ ID NO: 159 is the cDNA sequence determined for P272 SEQ ID NO: 160 is the cDNA sequence determined for P278 SEQ ID NO: 161 is the cDNA sequence determined for P105 SEQ ID NO: 162 is the cDNA sequence determined for P107 SEQ ID NO: 163 is the cDNA sequence determined for P137 SEQ ID NO: 164 is the cDNA sequence determined for P194 SEQ ID NO: 165 is the sequence of cDNA determined for P195 SEQ ID NO: 166 is the cDNA sequence determined for P196 SEQ ID NO: 167 is the cDNA sequence determined for P220 SEQ ID NO: 168 is the cDNA sequence determined for P234 SEQ ID NO: 169 is the cDNA sequence determined for P235 SEQ ID NO: 170 is the cDNA sequence determined for P243 SEQ ID NO: 171 is the cDNA sequence determined for P703P-DE1
SEQ ID NO: 172 is the amino acid sequence predicted for P703P-DE1 SEQ ID NO: 173 is the cDNA sequence determined for P703-DE2
SEQ ID NO: 174 is the cDNA sequence determined for P703-DE6
SEQ ID NO: 175 is the cDNA sequence determined for P703-DE13
SEQ ID NO: 176 is the amino acid sequence predicted for P703-DE13 SEQ ID NO: 177 is the cDNA sequence determined for P703P-DE14
SEQ ID NO: 178 is the predicted amino acid sequence for P703P-DE14 SEQ ID NO: 179 is the extended cDNA sequence determined for 1G-4736 SEQ ID NO: 180 is the extended cDNA sequence determined for
1G-4738 SEQ ID NO: 181 is the extended cDNA sequence determined for 1G-4741 5 SEQ ID NO: 182 is the extended cDNA sequence determined for
1G-4744 SEQ ID NO: 183 is the extended cDNA sequence determined for
1H-4774 SEQ ID NO: 184 is the extended cDNA sequence determined for 10 1H-4781 ^ SEQ ID NO: 185 is the extended cDNA sequence determined for
1H-4785 SEQ ID NO: 186 is the extended cDNA sequence determined for
1H-4787 15 SEQ ID NO: 187 is the extended cDNA sequence determined for
1H-4796 SEQ ID NO: 188 is the extended cDNA sequence determined for
11-4807 SEQ ID NO: 189 is the extended cDNA sequence determined for 20 11-4310 SEQ ID NO: 190 is the 3 'cDNA sequence determined for 11-4811
SEQ ID MO: 191 is the extended cDNA sequence determined for
1J-4876 SEQ ID NO: 192 is the extended cDNA sequence determined for 25 1K-4S34 SEQ ID NO: 193 is the extended cDNA sequence determined for
1K-4896 SEQ ID NO: 194 is the extended cDNA sequence determined for
SEQ ID NO: 195 is the extended cDNA sequence determined for
1G-4762 SEQ ID NO: 196 is the extended cDNA sequence determined for
1H-4766 SEQ ID NO: 197 is the 3 'cDNA sequence determined for 1H-4770 10 SEQ ID NO: 198 is the 3' cDNA sequence determined for 1H-4771
SEQ ID NO: 199 is the extended cDNA sequence determined for
1H-4772 SEQ ID NO: 200 is the extended cDNA sequence determined for
1D-4309 15 SEQ ID NO: 201 is the extended cDNA sequence determined for
ID.1-4278 SEQ ID NO: 202 is the extended cDNA sequence determined for
1D-4288 f SEQ ID NO: 203 is the extended cDNA sequence determined for 20 1D-4283 SEQ ID NO: 204 is the extended cDNA sequence determined for
1D-4304 SEQ ID NO: 205 is the extended cDNA sequence determined for
1D-4296 SEQ ID NO: 206 is the extended cDNA sequence determined for 1D-4280 SEQ ID NO: 207 is the cDNA sequence determined for 10-d8fwd
SEQ ID NO: 208 is the cDNA sequence determined for 10-H10 with SEQ ID NO: 209 is the cDNA sequence determined for ll-C8rev
SEQ ID NO: 210 is the cDNA sequence determined for 7.g6fwd
SEQ ID NO: 211 is the cDNA sequence determined for 7.g6rev
SEQ ID NO: 212 is the cDNA sequence determined for 8-b5fwd
SEQ ID NO: 213 is the cDNA sequence determined for 8-b5rev SEQ ID NO: 214 is the cDNA sequence determined for 8-b6fwd
SEQ ID NO: 215 is the cDNA sequence determined for 8-b6 rev
SEQ ID NO: 216 is the cDNA sequence determined for 8-d4fwd
SEQ ID NO: 217 is the cDNA sequence determined for 8-d9rev
SEQ ID NO: 218 is the cDNA sequence determined for 8-g3fwd SEQ ID NO: 219 is the cDNA sequence determined for 8-g3rev
SEQ ID NO: 220 is the cDNA sequence determined for 8-hllrev
SEQ ID NO: 221 is the cDNA sequence determined for g-fll2fwd
SEQ ID NO: 222 is the cDNA sequence determined for g-f3rev
SEQ ID NO: 223 is the cDNA sequence determined for P509S SEQ ID NO: 224 is the cDNA sequence determined for P510S
SEQ ID NO: 225 is the cDNA sequence determined for P703DE5
SEQ ID NO: 226 is the cDNA sequence determined for 9-A11
SEQ ID NO: 227 is the cDNA sequence determined for 8-C6 SEQ ID NO: 228 is the cDNA sequence determined for 8-H7 SEQ ID NO: 229 is the cDNA sequence determined for JPTPN13 SEQ ID NO: 230 is the cDNA sequence determined for JPTPN14
SEQ ID NO: 231 is the cDNA sequence determined for JPTPN23
SEQ ID NO: 232 is the cDNA sequence determined for JPTPN24
SEQ ID NO: 233 is the cDNA sequence determined for JPTPN25 SEQ ID NO: 234 is the cDNA sequence determined for JPTPN30
SEQ ID NO: 235 is the cDNA sequence determined for JPTPN34
SEQ ID NO: 236 is the cDNA sequence determined for PTPN35
SEQ ID NO: 237 is the cDNA sequence determined for JPTPN36
SEQ ID NO: 238 is the cDNA sequence determined for JPTPN38 SEQ ID NO: 239 is the cDNA sequence determined for JPTPN39
SEQ ID NO: 240 is the cDNA sequence determined for JPTPN40
SEQ ID NO: 241 is the cDNA sequence determined for JPTPN41
SEQ ID NO: 242 is the cDNA sequence determined for JPTPN42
SEQ ID NO: 243 is the cDNA sequence determined for JPTPN45 SEQ ID NO: 244 is the cDNA sequence determined for JPTPN46
SEQ ID NO: 245 is the cDNA sequence determined for JPTPN51
SEQ ID NO: 246 is the cDNA sequence determined for JPTPN56
SEQ ID NO: 247 is the cDNA sequence determined for PTPN64
SEQ ID NO: 248 is the cDNA sequence determined for JPTPN65 SEQ ID NO: 249 is the cDNA sequence determined for JPTPN67
SEQ ID NO: 250 is the cDNA sequence determined for JPTPN76
SEQ ID NO: 251 is the cDNA sequence determined for JPTPN84
SEQ ID NO: 252 is the cDNA sequence determined for JPTPN85
SEQ ID NO: 253 is the cDNA sequence determined for JPTPN86 SEQ ID NO: 254 is the cDNA sequence determined for JPTPN87 SEQ ID NO: 255 is the cDNA sequence determined for JPTPN8E SEQ ID NO: 256 is the cDNA sequence determined for JP1F1 SEQ ID NO: 257 is the cDNA sequence determined for JP1F2 f SEQ ID NO: 258 is the cDNA sequence determined for JP1C2 5 SEQ ID NO: 259 is the cDNA sequence determined for JP1B1 SEQ ID NO: 260 is the cDNA sequence determined for JP1B2 SEQ ID NO: 261 is the determined cDNA sequence for JP1D3 SEQ ID NO: 262 is the cDNA sequence determined for JP1A4 SEQ ID NO: 263 is the cDNA sequence determined for JP1F5 10 SEQ ID NO: 264 is the cDNA sequence determined for JP1E6 f SEQ ID NO: 265 is the cDNA sequence determined for JP1D6 SEQ ID NO: 266 is the cDNA sequence determined for JP1B5 SEQ ID NO: 267 is the cDNA sequence determined for JP1A6 SEQ ID NO: 268 is the cDNA sequence determined for JP1E8 15 SEQ ID NO: 269 is the cDNA sequence determined p for JP1D7 SEQ ID NO: 270 is the cDNA sequence determined for JP1D9 SEQ ID NO: 271 is the cDNA sequence determined for JP1C10 SEQ ID NO: 272 is the cDNA sequence determined for JP1A9 SEQ ID NO: 273 is the sequence of cDNA determined for JP1F12
SEQ ID NO: 274 is the cDNA sequence determined for JP1E12 SEQ ID NO: 275 is the cDNA sequence determined for JP1D11 SEQ ID NO: 276 is the cDNA sequence determined for JPlCll SEQ ID NO: 277 is the cDNA sequence determined for JP1C12 SEQ ID NO: 278 is the cDNA sequence determined for JP1B12
SEQ ID NO: 279 is the cDNA sequence determined for JP1A12 SEQ ID NO: 280 is the cDNA sequence determined for JP8G2
SEQ ID NO: 281 is the cDNA sequence determined for JP8H1
SEQ ID NO: 282 is the cDNA sequence determined for JP8H2
SEQ ID NO: 283 is the cDNA sequence determined for JP8A3 SEQ ID NO: 284 is the cDNA sequence determined for JP8A4
SEQ ID NO: 285 is the cDNA sequence determined for JP8C3
SEQ ID NO: 286 is the cDNA sequence determined for JP8G4
SEQ ID NO: 287 is the cDNA sequence determined for JP8B6
SEQ ID NO: 288 is the cDNA sequence determined for JP8D6 SEQ ID NO: 289 is the cDNA sequence determined for JP8F5
SEQ ID NO: 290 is the cDNA sequence determined for JP8A8
SEQ ID NO: 291 is the cDNA sequence determined for JP8C7
SEQ ID NO: 292 is the cDNA sequence determined for JP8D7
SEQ ID NO: 293 is the cDNA sequence determined for P8D8 SEQ ID NO: 294 is the cDNA sequence determined for JP8E7
SEQ ID NO: 295 is the cDNA sequence determined for JP8F8
SEQ ID NO: 296 is the cDNA sequence determined for JP8G8
SEQ ID NO: 297 is the cDNA sequence determined for JP8B10
SEQ ID NO: 298 is the cDNA sequence determined for JP8C10 SEQ ID NO: 299 is the cDNA sequence determined for JP8E9
SEQ ID NO: 300 is the cDNA sequence determined for JP8E10
SEQ ID NO: 301 is the cDNA sequence determined for JP8F9
SEQ ID NO: 302 is the cDNA sequence determined for JP8H9
SEQ ID NO: 303 is the cDNA sequence determined for JP8C12 SEQ ID NO: 304 is the cDNA sequence determined for JP8E11 SEQ ID NO: 305 is the cDNA sequence determined for JP8E12 SEQ ID NO: 306 is the amino acid sequence for peptide PS2 # 12 f SEQ ID NO: 307 is the cDNA sequence determined for P711P 5 SEQ ID NO: 308 is the cDNA sequence determined for P712P SEQ ID NO: 309 is the cDNA sequence determined for CLONE23 SEQ ID NO: 310 is the cDNA sequence determined for P774P SEQ ID NO: 311 is the cDNA sequence determined for P775P SEQ ID NO: 312 is the cDNA sequence determined for P715P 10 SEQ ID NO: 313 is the cDNA sequence determined for P710P SEQ ID NO: 314 is the cDNA sequence determined for P767P SEQ ID NO: 315 is the cDNA sequence determined for P768P SEQ ID NO: 316-325 are the cDNA sequences determined from previously isolated genes 15 SEQ ID NO: 326 is the cDNA sequence determined for P703PDE5 SE Q ID NO: 327 is the amino acid sequence predicted for
P703PDE5 SEQ ID NO: 328 is the cDNA sequence determined for P703P6.26 f SEQ ID NO: 329 is the amino acid sequence predicted for
P703P6.26 SEQ ID NO: 330 is the cDNA sequence determined for P703PX-23 SEQ ID NO: 331 is the amino acid sequence predicted for
P703PX-23 SEQ ID NO: 332 is the full-length cDNA sequence
determined for P509S SEQ ID NO: 333 is the extended cDNA sequence determined for P707P (also referred to as 11-C9) SEQ ID NO: 334 is the cDNA sequence determined for P714P
f SEQ ID NO: 335 is the cDNA sequence determined for P705P 5 (also referred to as 9-F3) SEQ ID NO: 336 is the predicted amino acid sequence for P705P SEQ ID NO: 337 is the amino acid sequence of the peptide P1S # 10 SEQ ID NO: 338 is the amino acid sequence of the p5 peptide SEQ ID NO: 339 is the predicted amino acid sequence of P590S 10 SEQ ID NO: 340 is the cDNA sequence determined for P778P SEQ ID NO: 341 is the sequence of cDNA determined for P786P SEQ ID NO: 342 is the determined cDNA sequence for P789P SEQ ID NO: 343 is the cDNA sequence determined for a clone showing homology to MM46 mRNA of Homo sapiens 15 SEQ ID NO: 344 is the cDNA sequence determined for a clone showing mRNA to ABC protein mRNA (ABC50 ) stimulated by Homo sapiens TNF-alpha SEQ ID NO: 345 is the cDNA sequence determined for a clone f that shows homology to Homo sapiens mRNA for E-cadherin 20 SEQ ID NO: 346 is the cDNA sequence determined for a clone showing homology to nuclear-encoded human mitochondrial serine hydroxymethyltransferase (SHMT) SEQ ID NO: 347 is the cDNA sequence determined for a clone showing protein-2-associated macrophage homology of
Natural resistance (NRAMP2) of Homo sapiens SEQ ID NO: 348 is the cDNA sequence determined for a clone showing homology to phosphoglucomutase-related protein (PGMRP) of Homo sapiens SEQ ID NO: 349 is the cDNA sequence determined for a clone 5 showing homology to human mRNA for proteasome p40 subunit SEQ ID NO: 350 is the cDNA sequence determined for P777P SEQ ID NO: 351 is the cDNA sequence determined for P779P SEQ ID NO: 352 is the determined cDNA sequence for P790P 10 SEQ ID NO: 353 is the cDNA sequence determined for P784P f SEQ ID NO: 354 is the cDNA sequence determined for P776P SEQ ID NO: 355 is the cDNA sequence determined for P780P SEQ ID NO: 356 is the cDNA sequence determined for P544S SEQ ID NO: 357 is the cDNA sequence determined for P745S SEQ ID NO: 358 is the cDNA sequence determined for P782P SEQ ID NO: 359 is the cDNA sequence determined for P783P SEQ ID NO: 360 is the cDNA sequence determined for unknown 17984 SEQ ID NO: 361 is the cDNA sequence determined for P787P SEQ ID NO: 362 is the cDNA sequence determined for P788P SEQ ID NO: 363 is the cDNA sequence determined for unknown 17994 SEQ ID NO: 364 is the cDNA sequence determined for P781P SEQ ID NO: 365 is the cDNA sequence determined for P785P SEQ ID NO: 366-375 are the cDNA sequences determined for splice variants of B305D SEQ ID NO: 376 is the predicted amino acid sequence encoded by the sequence of SEQ ID NO: 366 5 SEQ ID NO: 377 is the predicted amino acid sequence encoded by the sequence of SEQ ID NO: 372 SEQ ID NO: 378 is the predicted amino acid sequence encoded by the sequence of SEQ ID NO: 373 SEQ ID NO: 379 is the predicted amino acid sequence encoded
by the sequence of SEQ ID NO: 374 SEQ ID NO: 380 is the predicted amino acid sequence encoded by the sequence of SEQ ID NO: 375 SEQ ID NO: 381 is the cDNA sequence determined for B716P
SEQ ID NO: 382 is the full-length cDNA sequence determined for P711P SEQ ID NO: 383 is the predicted amino acid sequence for P711P
SEQ ID NO: 384 is the cDNA sequence for P1000C SEQ ID NO: 385 is the cDNA sequence for CGI-82 SEQ ID NO: 386 is the cDNA sequence for 23320 SEQ ID NO: 387 is the cDNA sequence for CGI-69 SEQ ID NO: 388 is the cDNA sequence for L-iditol-2-dehydrogenase SEQ ID NO: 389 is the cDNA sequence for 23379 SEQ ID NO: 390 is the cDNA sequence for 23381 SEQ ID NO: 391 is the cDNA sequence for KIAA0122 SEQ ID NO: 392 is the cDNA sequence for 23399 SEQ ID NO: 393 is the cDNA sequence for a previously identified gene SEQ ID NO: 394 is the cDNA sequence for HCLBP SEQ ID NO : 395 is the cDNA sequence for transglutaminase SEQ ID NO: 396 is the cDNA sequence for a previously identified gene SEQ ID NO: 397 is the cDNA sequence for PAP SEQ ID NO: 398 is the cDNA sequence for transcription factor Ets PDEF SEQ ID NO: 399 is the cDNA sequence for hTGR SEQ ID NO: 400 is the cDNA sequence for KIAA0295 SEQ ID NO : 401 is the cDNA sequence for 22545 SEQ ID NO: 402 is the cDNA sequence for 22547 SEQ ID NO: 403 is the cDNA sequence for 22548 SEQ ID NO: 404 is the cDNA sequence for 22550 SEQ ID NO: 405 is the cDNA sequence for 22551 SEQ ID NO: 406 is the cDNA sequence for 22552 SEQ ID NO: 407 is the cDNA sequence for 22553 SEQ ID NO: 408 is the cDNA sequence for 22558 SEQ ID NO: 409 is the cDNA sequence for 22562 SEQ ID NO: 410 is the cDNA sequence for 22565 SEQ ID NO: 411 is the cDNA sequence for 22567 SEQ ID NO: 412 is the cDNA sequence for 22568 SEQ ID NO: 413 is the sequence for cDNA for 22570 SEQ ID NO: 414 is the cDNA sequence for 22571
SEQ ID NO: 415 is the cDNA sequence for 22572
SEQ ID NO: 416 is the cDNA sequence for 22573
SEQ ID NO: 417 is the cDNA sequence for 22573 SEQ ID NO: 418 is the cDNA sequence for 22575
SEQ ID NO: 419 is the cDNA sequence for 22580
SEQ ID NO: 420 is the cDNA sequence for 22581
SEQ ID NO: 421 is the cDNA sequence for 22582
SEQ ID NO: 422 is the cDNA sequence for 22583 SEQ ID NO: 423 is the cDNA sequence for 22584
SEQ ID NO: 424 is the cDNA sequence for 22585
SEQ ID NO: 425 is the cDNA sequence for 22586
SEQ ID NO: 426 is the cDNA sequence for 22587
SEQ ID NO: 427 is the cDNA sequence for 22588 SEQ ID NO: 428 is the cDNA sequence for 22589
SEQ ID NO: 429 is the cDNA sequence for 22590
SEQ ID NO: 430 is the cDNA sequence for 22591
SEQ ID NO: 431 is the cDNA sequence for 22592
SEQ ID NO: 432 is the cDNA sequence for 22593 SEQ ID NO: 433 is the cDNA sequence for 22594
S? Q ID NO: 434 is the cDNA sequence for 22595
SEQ ID NO: 435 is the cDNA sequence for 22596
SEQ ID NO: 436 is the cDNA sequence for 22847
SEQ ID NO: 437 is the cDNA sequence for 22848 SEQ ID NO: 438 is the cDNA sequence for 22849 SEQ ID NO: 439 is the cDNA sequence for 22851 SEQ ID NO: 440 is the cDNA sequence for 22852 SEQ ID NO: 441 is the cDNA sequence for 22853 SEQ ID NO: 442 is the cDNA sequence for 22854 SEQ ID NO: 443 is the cDNA sequence for 22855 SEQ ID NO: 444 is the cDNA sequence for 22856 SEQ ID NO: 445 is the cDNA sequence for 22857 SEQ ID NO: 446 is the cDNA sequence for 23601 SEQ ID NO: 447 is the cDNA sequence for 23602 SEQ ID NO: 448 is the cDNA sequence for 23605 SEQ ID NO: 449 is the cDNA sequence for 23606 SEQ ID NO: 450 is the cDNA sequence for 23612 SEQ ID NO: 451 is the cDNA sequence for 23614 SEQ ID NO: 452 is the cDNA sequence for 23618 SEQ ID NO: 453 is the sequence of cDNA for 23622 SEQ ID NO: 454 is the cDNA sequence for folate hydrolase SEQ ID NO: 455 is the cDNA sequence for protein LIM SEQ ID NO: 456 is the cDNA sequence for a known gene SEQ ID NO: 457 is the cDNA sequence for a known gene SEQ ID NO: 458 is the cDNA sequence for a previously identified gene SEQ ID NO: 459 is the cDNA sequence for 23045 SEQ ID NO: 460 is the cDNA sequence for 23032 SEQ ID NO: 461 is the cDNA sequence for 23054 SEQ ID NO: 462-467 are the cDN.A sequences for known genes SEQ ID NO: 468-471 are the sequences of cDNA for P710P SEQ ID NO: 472 is the cDNA sequence for P1001C
DETAILED DESCRIPTION OF THE INVENTION As noted above, the present invention is generally digested to compositions and methods for cancer therapy and diagnosis, such as prostate cancer. The compositions described herein may include prostate tumor polypeptides, polynucleotides encoding such polypeptides, binding agents such as antibodies, antigen presenting cells (APCs) and / or immune system cells (e.g., T cells). the polypeptides of the present invention generally comprise at least a portion (such as, an immunogenic portion) of a prostate tumor protein or a variant thereof. A "prostate tumor protein" is a protein that is expressed in prostate tumor cells at a level that is at least two times, and preferably at least five times higher than the level of expression in a normal tissue, as determined using a representative assay provided herein. Certain prostate tumor proteins are tumor proteins that react in a detectable manner (within an immunoassay, such as an ELISA or Western blot) with antisera from a patient afflicted with prostate cancer. The polynucleotides of the present invention generally comprise a DNA or RNA sequence that encodes all or a portion of such a polypeptide, or that is complementary to such a sequence. Antibodies are usually immune system proteins or antigen-binding fragments thereof, which are capable of binding to a polypeptide as described above. Antigen-presenting cells include dendritic cells, macrophages, monocytes, fibroblasts, and B cells that express a polypeptide as described above. T cells that can be employed within such compositions are generally T cells that are specific for a polypeptide as described above. The present invention is based on the discovery of human prostate tumor proteins. Polynucleotide sequences that encode certain tumor proteins, or portions thereof, are provided in SEQ ID Nos: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472. Polypeptide sequences comprising at least a portion of tumor protein are provided in SEQ ID NOS: 112-114, 172, 176, 178, 327, 329, 331, 336, 339, 376-380 and 383.
PROSTATE TUMOR PROTEIN POLYUCLEOTIDES Any polynucleotide that encodes a prostate tumor protein or a portion or other variant thereof as described herein, is encompassed by the present invention.
Preferred polynucleotides comprise at least 15 consecutive nucleotides, preferably at least 30 consecutive nucleotides and more preferably at least 45 consecutive nucleotides, which encode a portion of a prostate tumor protein. Most preferably, a polynucleotide encodes an immunogenic portion of a prostate tumor protein. Polynucleotides complementary to any such sequence are also encompassed by the present invention. the polynucleotides can be single filament (coding or antisense) or double filament, and can be DNA molecules (genomic, cDNA or synthetic) or RNA. RNA molecules include HnRNA molecules, which contain introns and correspond to a DNA molecule in a one-to-one manner, and mRNA molecules, which do not contain introns. Additional coding or non-coding sequences may be present, but not necessarily, within a polynucleotide of the present invention, and a polynucleotide may be linked, but not necessarily, to other molecules and / or support materials. The polynucleotides can comprise a natural sequence (i.e., an endogenous sequence that encodes a prostate tumor protein or a portion thereof) or can comprise a variant of such a sequence. The polynucleotide variants may contain one or more substitutions, assestions, deletions and / or insertions, so that the immunogenicity of the encoded polypeptide is not diminished, relative to a natural tumor protein. The effect on the immunogenicity of the encoded polypeptide can generally be assessed as described herein. The variants preferably exhibit at least about 70% identity, more preferably at least about 80% identity and most preferably at least about 90% identity to a polynucleotide sequence encoding a natural prostate tumor protein or a portion thereof. It is said that two polynucleotide or polypeptide sequences are "identical" if the sequence of nucleotides or amino acids in the two sequences are the same when aligned for maximum correspondence as described below. Comparisons between two sequences are usually made by comparing the sequences on a comparison window to identify and compare local regions of sequence similarity. A "comparison window", as used herein, refers to a segment of at least about 20 contiguous positions, usually 30 to about 75, 40 to about 50, in which a sequence can be compared to a reference sequence. of the same number of contiguous positions after the two sequences are optimally aligned. Optimal alignment of sequences for comparison can be conducted using the Megalign program in the Lasergene suite of the bioinformatics computation program (DNASTAR, Inc., Madison, Wl) using omission parameters. This program covers several alignment schemes described in the following references: Dayhoff, M.O. (1978) A model of evolutionary change in proteins -Matrices for detecting distant relationships. (A model of change evolve it into proteins - Matrices to detect distant relationships). In Dayhoff, M.O. (ed.) Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, Washington DC Vol. 5, Suppl. 3, pp, 345-358; Hein J. (1990) Unified Approach to Alignment and Phylogenes (unified approach to alignment and phylogenes) pp. 626-645 Methods in Enzymology vol. 183, Academic Press, Inc., San Diego, CA; Higgins, D.G. and Sharp. P.M. (1989) CABIOS 5: 151-153; Myers, E.W. and Muller W. (1988) CABIOS 4: 11-17; Robinson, E.D. (1971) Comb. Theor. 11: 105; Santou, N. Nes, M. (1987) Mol. Biol. Evol. 4: 406-425; Sneath, P.H. A. and Sokal, R.R. (1973) Numerical Taxonomy - the Principles and Practice of Numerical Taxonomy, (Numerical Taxonomy - Principles and Practice of Numerical Taxonomy), Freeman Press, San Francisco, CA; Wilbur, W.J., and Lipman, D.J. (1983) Proc. Na ti. Acad. Sci. USA 80: 726-730. Preferably, the "percent sequence identity" is determined by comparing two optimally aligned sequences on a comparison window of at least 20 positions, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (ie, holes) of 20 percent or less, usually 5 to 15 percent, or 10 to 12 percent, as compared to the reference sequence (which does not include additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions in which the identical nucleic acid or amino acid residue bases occur in both sequences, to produce the number of equalized positions, dividing the number of positions equalized by the total number of positions in the reference sequence (that is, the size of the window) and multiply the results by 100 to produce the percentage of sequence identity. The variants also, or alternatively, may be substantially homologous to a natural gene or a portion or complement thereof. Such variants of polynucleotides are capable of hybridizing under moderately severe conditions to a naturally occurring DNA sequence encoding a natural prostate tumor protein (or a complementary sequence). Suitable moderately severe conditions include, prewash in a solution of 5X SSC, 0.5% SDS, 1.0 mM EDTA (pH8.0); hybridize at 50 ° C-65 ° C, 5 X SSC, overnight; followed by washing twice at 65 ° C for 20 minutes each with 2X, 0.5X and 0.2X SSC containing 0.1% SDS. Those of ordinary skill in the art will appreciate that, as a result of the degeneracy of the genetic code, there are many nucleotide sequences encoding a polypeptide as described herein. Some of these polmucleotides support minimal homology to the nucleotide sequence of any natural gene. However, polynucleotides that vary due to differences in codon usage are specifically contemplated by the present invention. In addition, alleles of the genes comprising the polynucleotide sequences provided herein are within the scope of the present invention. Alleles are endogenous genes that are altered as a result of one or more mutations, such as deletions, additions and / or substitutions of nucleotides. The resulting mRNA and protein may have, but not necessarily, an altered structure or function. The alleles can be identified using standard techniques (such as, hybridization, amplification and / or comparison of database sequences). The polynucleotides can be prepared using any of a variety of techniques. For example, a polynucleotide can be identified, as described in more detail below, by classifying a microarray of cDNAs for tumor-associated expression (i.e. expression that is at least five times higher in a prostate tumor than in normal tissue). , as determined using a representative assay provided herein). Such screens can be made using a Synteni microarray (Palo Alto, CA) according to the manufacturer's instructions (and essentially as described by Schena et al., Proc. Na ti. Acad. Sci. USA 93: 10614-10619 , 1996 and Heller et al., Proc. Na ti. Acad. Sci. USA 94: 2150-2155, 1997). Alternatively, the polypeptides can be amplified from cDNA prepared from cells expressing the proteins described herein, such as, prostate tumor cells. Such polynucleotides can be amplified via polymerase chain reaction (PCR). For this approach, sequence specific primers can be designed based on the sequences provided herein, and can be purchased or synthesized. An amplified portion can be used to isolate a full-length gene from a suitable library (e.g., a prostate tumor cDNA library) using well-known techniques. Within such techniques, a library (cDNA or genomic) is classified using one or more polynucleotide probes or primers suitable for amplification. Preferably, a library is selected by size to include larger molecules. Randomly initiated libraries may also be preferred to identify 5 'and upstream gene regions. Genomic libraries are preferred to obtain introns and 5 'extension sequences. For hybridization techniques, a partial sequence can be labeled (e.g., by nick translation or terminal labeling with 3 ~ P) using well-known techniques. A bacterial or bacteriophage library is then classified by hybridizing filters containing denatured bacterial colonies (or phage plaques containing fields) with the labeled probe (see Sambrook et al., Molecular Cloning: A Labora tory Manua l (Molecular cloning: a manual of laboratory), Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989). The colonies or hybridization plates are selected and expanded, and the DNA is isolated for further analysis. The cDNA clones can be analyzed to determine the amount of additional sequence by, for example, PCR using a partial sequence primer and a vector primer. Restriction maps and partial sequences can be generated to identify one or more clones that overlap. The entire sequence can then be determined using standard techniques, which may involve generating a series of deletion clones. The resulting overlap sequences are then mounted in a simple contiguous sequence. A full-length cDNA molecule can be generated by ligating suitable fragments, using well-known techniques. Alternatively, there are numerous amplification techniques to obtain a full-length sequence from a partial cDNA sequence. Within such techniques, amplification is generally carried out via PCR. Any of a variety of commercially available assemblies can be used to perform the amplification step. The primers can be designed using, for example, computer program well known in the art. The primers are preferably 22-30 nucleotides in length, have a GC content of at least 50% and anneal the target sequence at temperatures of about 68 ° C to 72 ° C. The amplified region can be sequenced as described above, and overlap sequences can be mounted in a contiguous sequence. An amplification technique is inverse PCR (see Triglia et al., Nucà Acids Res. 16: 8186, 1988), which uses restriction enzymes to generate a fragment in the known region of the gene. The fragment is then circulated by intramolecular ligation and used as a template for PCR with divergent primers derived from the known region. Within an alternative approach, sequences adjacent to a partial sequence can be recovered by amplification with an initiator to a linker sequence and a specific primer for a known region. The amplified sequences are normally subjected to a second round of amplification with the same linker primer and a second primer specific for the known region. A variation on this procedure, which employs two primers that begin extension in opposite directions of the known sequence, is described in WO 96/38591. Another technique is known as "rapid amplification of cDNA ends" or RACE. This technique involves the use of an internal primer and an external primer, which hybridizes to a vector sequence or polyA region, to identify sequences that are 5 'and 3' of a known sequence. Additional techniques include capture PCR (Lagerstrom et al., PCR Methods Appl ic.1: 111-19, 1991) and walk PCR (Parker et al., Nucà Acids Res. 19: 3055-60, 1991). Other methods that employ amplification can also be employed to obtain a full-length cDNA sequence. In certain cases, it is possible to obtain a full-length cDNA sequence by analyzing sequences provided in an expressed sequence tag (EST) database, such as that available from GenBank. Searches for overlapping ESTs can generally be performed using well-known programs (eg, NCBI BLAST searches), and such ESTs can be used to generate an adjoining full-length sequence. Certain nucleic acid sequences of cDNA molecules that encode at least a portion of a prostate tumor protein are provided in SEQ ID Nos: 1-111, 115-171, 173-175, 177, 179-305, 307-315 , 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472. The isolation of these polynucleotides is described below. Each of these prostate tumor proteins was overexpressed in prostate tumor tissue. Variants of polynucleotides can generally be prepared by any method known in the art, including chemical synthesis by, for example, chemical synthesis of solid phase phosphoramidite. Modifications in a polynucleotide sequence can also be introduced using standard mutagenesis techniques, such as specific, site-directed mutagenesis with oligonucleotide (see Adelman et al., DXA 2: 183, 1983). Alternatively, RNA molecules can be generated by in vitro or in vivo transcription of DNA sequences encoding a prostate tumor protein, or portion thereof, as long as the DNA is incorporated into a vector with a polymerase promoter. of adequate RNA (such as, T7 or SP6). Certain portions can be used to prepare a coded polypeptide, as described herein. In addition, or alternatively, a portion may be administered to a patient, such that the encoded polypeptide is generated m vivo (e.g., by transfecting antigen-presenting cells, such as, dendritic cells, with a cDNA construct that encodes a prostate tumor polypeptide, and administer the transfected cells to the patient). A portion of a sequence complementary to a coding sequence (ie, an antisense polynucleotide) can also be used as a probe or to modulate gene expression. The cDNA constructs that can be transcribed into antisense RNA can also be introduced into tissue cells to facilitate the production of antisense RNA. An antisense polynucleotide, as described herein, can be used to inhibit the expression of a tumor protein. Antisense technology can be used to control gene expression through triple helical forging, which compromises the capacity of the double helix to open sufficiently for the binding of polymerases, transcription factors or regulatory molecules (see Gee et al., in Huoer and Carr, Molecu la r and Im unologic Approa ches (Molecular and molecular approaches), Futura Publishing Co. (Mt. Kisco, NY; 1994)). Alternatively, an antisense molecule can be designed to hybridize to a control region of a gene (e.g., promoter, enhancer or transcription initiation site) and gene block transcription; or to block translation by inhibiting the binding of a transcript to ribosomes. A portion of a coding sequence, or a complementary sequence, may also be designed as a probe or primer to detect gene expression. The probes can be labeled with a variety of reporter groups, such as radionuclides and enzymes, and are preferably at least 10 nucleotides in length, more preferably at least 20 nucleotides in length and even more preferably at least 30 nucleotides in length. length. The primers, as noted above, are preferably 22-30 nucleotides in length. Any polynucleotide can be further modified to increase the stability in vivo. Possible modifications include, but are not limited to, the addition of 0 flanking sequences at the 5 'and / or 3' ends, the use of phosphorothioate or 2'O-methyl in place of phosphodiesterase bonds in the backbone, and / or the inclusion of non-traditional bases, such as, mosma, cheosin and wentesma, as well as acetyl-, methyl-, thio- and other modified forms of acenin, citidma, guanine, D-thymine and updina. Nucleotide sequences as described in the present can be attached to a variety of other nucleotide sequences using established recombinant DNA techniques. For example, a polynucleotide can be cloned into any of a variety of cloning vectors, including plasmids, fagomids, lambda phage derivatives and cosmids. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors and sequencing vectors. In general, a vector will contain a functional origin of replication in at least one organism, convincing restriction endonuclease sites and one or more selectable markers. Other elements will depend on the intended use and will be apparent to those of ordinary skill in the art. Within certain embodiments, the polynucleotides can be formulated in order to allow entry into a mammalian cell and expression therein. Such formulations are particularly useful for therapeutic purposes, as described below. Those of ordinary skill in the art will appreciate that there are many ways to achieve the expression of a polynucleotide in a target cell and any suitable method can be employed. For example, a polynucleotide can be incorporated into a viral vector, such as, but not limited to, adenovirus, adeno-associated virus, retrovirus or vaccinia or other pustular virus (eg, pustular bird virus). Techniques for incorporating DNA into such vectors are well known to those of ordinary skill in the art. A retroviral vector can additionally transfer or incorporate a gene for a selectable marker (to aid in the identification or selection of transduced cells) and / or a targeting portion, such as a gene encoding a ligand for a receptor in a target cell specifies, to make the target vector specific. Targeting can also be achieved using an antibody, by methods known to those of ordinary skill in the art. Other formulations for therapeutic purposes include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles and liposomes. A preferred colloidal system for use as an in vitro or in vivo delivery vehicle is a liposome (i.e., an artificial membrane vesicle). The preparation and use of such systems is well known in the art.
PROSTATE TUMOR POLYPEPTIDES Within the context of the present invention, the polypeptides may comprise at least an immunogenic portion of a prostate tumor ur protein or a variant thereof, as described herein. As noted above, a "prostate tumor protein" is a protein that is expressed by prostate tumor cells. Proteins that are prostate tumor proteins also react detectably within an immunoassay (such as an ELISA) with antiserum from a patient with prostate cancer. The polypeptides, as described herein, may be of any length. Additional sequences derived from the native protein and / or heterologous sequences may be present, and such sequences may possess (but not necessarily) additional immunogenic or antigenic properties. An "immunogenic portion", as used herein, is a portion of a protein that is recognized (i.e., specifically bound) by a B cell and / or T cell surface antigen receptor. Such immunogenic portions generally comprise at least 5 amino acid residues, more preferably at least 10, and still more preferably at least 20 amino acid residues of a prostate tumor protein or a variant thereof. Certain preferred immunogenic portions include peptides in which an N-terminal leader sequence and / or transmembrane domain have been deleted. Other preferred immunogenic portions may contain a small N- and / or C-terminal deletion (eg, 1-30 amino acids, preferably 5-15 amino acids), relative to the mature protein. Generally, immunogenic portions can be identified using well known techniques, such as those summarized in Paul, Fundamen tal Immunol ogy, 3rd ed. 243-247 (Raven Press, 1993) and references cited therein. Such techniques include classifying peptides for the ability to react with antigen-specific antibodies, antisera and / or T-cell lines or clones. As used herein, antisera and antibodies are "antigen-specific" if they specifically bind to an antigen (i.e., they react with the protein in an ELISA or other immunoassay, and do not react detectably with unrelated proteins) . Such antisera and antibodies can be prepared as described herein, and using well-known techniques. Such an immunogenic portion of a natural prostate tumor protein is a portion that reacts with such antisera and / or T cells at a level that is not substantially less than the reactivity of the full-length polypeptide (e.g., in an ELISA assay and / or T cell reactivity). Such immunogenic portions can react within such assays at a level that is similar to, or greater than, the reactivity of the full-length polypeptide. Such classifications can generally be made using methods well known to those of ordinary skill in the art, such as those described in Harlow and Lane, An t ibodies: A Labora tory Manual (Antibodies: a laboratory manual), Cold Spring Harbor Laboratory , 1988. For example, a polypeptide can be immobilized on a solid support and can be contacted with patient serum to allow binding of antibodies within the serum to the immobilized polypeptide. Unbound serum can then be removed and bound antibodies can be detected using, for example, Protein A labeled with 125I. As noted above, a composition may comprise a variant of a natural prostate tumor protein. A "variant" polypeptide, as used herein, is a polypeptide that differs from a natural prostate tumor protein in one or more substitutions, deletions, additions and / or insertions, so that the immunogenicity of the polypeptide is not
is substantially diminished. In other words, the ability f of a variant to react with antigen-specific antiserum may be enhanced or not changed, relative to the natural protein, or may be decreased by less than 50%, and preferably less than 20% relative to the natural protein Such
variants can generally be identified by modifying one of the above polypeptide sequences, and evaluating the reactivity of the modified polypeptide with antibodies and antigen-specific antisera, as described in f present. Preferred variants include those in the
Wherein one or more portions, such as an N-terminal leader sequence or transmembrane domain, have been removed. Other preferred variants include variants in which a small portion (eg, 1-30 amino acids, preferably 5-15 amino acids) of the N- and / or C-terminus of ia has been removed.
mature protein. Polypeptide-markers preferably exhibit at least about 70%, more preferably at least about 90% and most preferably at least about 95% identity (determined as described above) to the identified polypeptides. Preferably, a variant contains conservative substitutions. A "conservative substitution" is one in which an amino acid is substituted by another amino acid having similar properties, so that one skilled in the art of peptide chemistry would expect the secondary structure and hydropathic nature of the polypeptide to remain substantially unchanged. Amino acid substitutions can generally be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and / or the amphipathic nature of the residues. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and argimine; and amino acids with uncharged polar head groups having similar hydrophilicity values include leucma, Ãsoleucma and valine, glycine and alanine; asparagma and glutamine; and serine, threonine, phenylalanine and tyrosine. Other groups of amino acids that may represent conservative changes include (1) ala, pro, gly, glu, asp, gln, asn, ser, thr, (2) cys, ser, tyr, tnr, (3) val, lie, leu , met, ala, ohe, (4) lys, arg, his, and (5) phe, tyr, trp, his. One can also, or alternatively, contain non-conservative changes. In a preferred embodiment, the variant polypeptides differ from a natural sequence by substitution, deletion or addition of five amino acids or less. The variants may also (or alternatively) be modified by, for example, the deletion or addition of amino acids that have minimal influence on the immunogenicity, secondary structure and hydropathic nature of the polypeptide. As noted above, the polypeptides may comprise a signal sequence (or leader) at the N-terminus of the
protein, which co-translationally or post-translationally directs the transfer of the protein. The polypeptide can also be conjugated to a linker or other sequence for ease of synthesis, purification or identification of the polypeptide (eg, poly-His) or to enhance binding
of the polypeptide to a solid support. For example, a polypeptide can be conjugated to an immunoglobulin Fc region. The polypeptides can be prepared using any of a variety of well-known techniques. The recombinant polypeptides encoded by DNA sequences, as described
above, can be easily prepared from the DNA sequences using any of a variety of expression vectors known to those of ordinary skill in the art. Expression can be achieved in any appropriate host cell that has been transformed or transfected with an expression vector
containing a DNA molecule encoding a recombinant polypeptide. Suitable host cells include prokaryotes, yeasts and higher eukaryotic cells. Preferably, the host cells employed are E. col i, yeasts or a line of f mammalian cells, such as, COS or CHO. The supernatants of
Suitable host / vector systems that secrete polypeptide or recombinant protein in culture media can be first concentrated using a commercially available filter. Following the concentration, the concentrate can be applied to a suitable purification matrix, such as an affinity matrix or a
ream of ion exchange. Finally, one or more steps of reverse phase HPLC can be used to further purify a recombinant polypeptide. The portions and other variants having less than about 100 amino acids, and generally less than
Approximately 50 amino acids can also be generated by synthetic means, using techniques well known to those of ordinary skill in the art. For example, such polypeptides can be synthesized using any of the commonly available solid phase techniques, such as,
solid phase synthesis method of Merrifield, where the amino acids are sequentially added to a chain of growing amino acids. See Merrifield, J. Am Chem. Soc. 85 2149-2146, 1963. The equipment for automated polymer synthesis is commercially available from suppliers such as Perkin Elmer / Applied BioSystems Division (Foster City, CA) and can be operated in accordance with the manufacturer's instructions. Within certain specific embodiments, a polypeptide can be a fusion protein comprising multiple polypeptides as described herein, or comprising at least one polypeptide as described herein and an unrelated sequence, such as a protein known tumor. A fusion partner can assist, for example, in providing T-helper epitopes (a fusion partner), preferably T-helper epitopes recognized by humans, or they can assist in expressing the protein (an expression enhancer) at higher yields than natural recombinant protein. Certain preferred fusion partners are fusion partners both in terms of mmunology and expression enhancers. Other fusion partners can be selected in order to increase the solubility of the protein or allow the protein to be targeted to desired cell compartments. Still other fusion partners include affinity tags, which facilitate the purification of the protein. Fusion proteins can generally be prepared using standard techniques, including chemical conjugation. Preferably, a fusion protein is expressed as a recombinant protein, allowing the production of increased levels, in relation to a non-merged UiOteina, in expression system. In brief, the DNA sequences encoding the polypeptide components can be assembled separately, and ligated into an appropriate expression vector. The 3 'end of the DNA sequence encoding a polypeptide component is ligated, with or without a peptide linker, to the 5' end of a DNA sequence encoding the second polypeptide component, such that the reading frames of the sequences are in phase. This allows translation in a simple fusion protein that retains the biological activity of both component polypeptides. A peptide linker sequence can be used to separate the first and second polypeptide components by a sufficient distance to ensure that each polypeptide is bent into its secondary and tertiary structures. Such a peptide linker sequence is incorporated into the fusion protein using standard techniques well known in the art. Such suitable peptide linker sequences can be chosen based on the following factors: (1) their ability to adopt a flexible extended conformation; (2) its inability to adopt a secondary structure that could interact with functional epitopes in the first and second polypeptides; and (3) the lack of hydrophobic or charged residues that could react with the functional polypeptide epitopes. Preferred peptide linker sequences contain residues of Gly, Asn and Ser. Other almost neutral amino acids, such as Thr and Ala, can also be used in the linker sequence. Amino acid sequences that can be usefully employed as linkers include those described in Maratea et al., Gene 40: 39-46, 1985; Murphy et al., Proc. Na ti. Acad. Sci. USA 83: 8258- 5 8262, 1986; US patent no. 4,935,233 and U.S. Patent No. 4,751,180. The linker sequence can generally be from 1 to about 50 amino acids in length. Linker sequences are not required when the first and second polypeptides have
regions of non-essential N-terminal amino acids that can be used to separate functional domains and prevent spherical interference. The ligated DNA sequences are operably linked to regulatory elements of transcription and translation
suitable. The regulatory elements responsible for DNA expression are located only 5 'for the DNA sequence encoding the first polypeptides. Similarly, the stop codons required for final translation and transcription termination signals are only present at 3 '
for the DNA sequence encoding the second polypeptide. Fusion proteins comprising a polypeptide of the present invention are also provided together with an unrelated immunogenic protein. Preferably, the immunogenic protein is capable of producing a recall response.
Examples of such proteins include tetanus, tuberculosis and hepatitis proteins (see, for example, Stoute et al., New Engl. J. Med., 336: 86-91, 1997). Within preferred embodiments, an immunological fusion partner is derived from protein D, a protein of
surface of the gram-negative bacterium Haemophilus influenza B
(WO 91/18926). Preferably, a protein D derivative comprises approximately the first third of the protein (e.g., the first 100-110 N-thermal amino acids) and a protein D derivative can be lipidated. Within certain
Preferred embodiments, the first 109 residues of a Lipoprotein D fusion partner is included at the N-terminus to provide the polypeptide with additional exogenous T-cell epitopes and to increase the level of expression in E. coli.
(functioning as well as an expression enhancer). He
The lipid appendage ensures the optical presentation of the antigen for cells that present antigen. Other fusion partners include the nonstructural protein of the mfluenzae virus, NS1
(hemagiutinin). Normally, the N-terminal 81 amino acids are used, although different fragments can be used.
include epitopes of T helpers. In another embodiment, the fusion partner is the protein known as LYTA, or a portion thereof, preferably a C-terminal portion. LYTA is derived from
Strep z ococcus pneumonia e, which synthesizes an N-acetyl-L-alanine
2 ^ > aiiiiQdsc: known as LYTA amidase (codified by the LytA gene, Gene 43: 265-292, 1986). LYTA is an autolysin that specifically degrades certain bonds in the peptidoglycan skeleton. The C-terminal domain of the LYTA protein is responsible for the affinity to choline or some choline analogs, such as DEAE. 5 This property has been exploited for the development of plasmids expressing C-LYTA of E. col i useful for the expression of fusion proteins. Purification of hybrid proteins containing the C-LYTA fragment at the amino terminus has been described (see Biotechnology 10: 795-798, 1992). Within a modality
Preferred, a repeated portion of LYTA can be incorporated into a fusion protein. A repeated portion is in the C-terminal region that starts at residue 178. A particularly preferred repeat portion incorporates residues 188-305. In general, polypeptides are isolated (including
fusion) and polynucleotides as described herein. An "isolated" polypeptide or polynucleotide is one that is removed from its original environment. For example, a protein that occurs naturally is isolated if it is separated from some or all of the coexisting materials in the natural system. Preferably,
Such polypeptides are at least about 90% pure, more preferably at least about 95% pure and most preferably at least about 99% pure. A polynucleotide is considered as isolated if, for example, it is cloned into a vector that is not part of the natural environment.
BINDING AGENTS The present invention further provides agents, such as antibodies and antigen-binding fragments thereof, that specifically bind to a prostate tumor protein. As used herein, an antibody, or antigen-binding fragment thereof, is said to "bind in a specific manner" to a prostate tumor protein if it reacts at a detectable level (within, for example, a ELISA) with a prostate reaction protein, and does not react detectably with unrelated proteins under similar conditions. As used herein, "binder" refers to a non-covalent association between two separate molecules, so that a complex is formed. The ability to bind can be evaluated by, for example, determining a binding constant for complex formation. The binding constant is the value obtained when the concentration of the complex is divided by the product of the component concentrations. In general, two compositions are said to "bind", in the context of the present invention, when the binding constant for complex formation exceeds about 103 1 / mol. The binding constant can be determined using methods well known in the art. Binding agents may additionally be able to differentiate between patients with and without a cancer, such as, prostate cancer, using the representative assays provided herein. In other words, antibodies or other binding agents that bind to a prostate tumor protein will generate a signal indicating the presence of a cancer in at least about 20% of patients with the disease, and will generate a negative signal indicating the absence of the disease in at least 90% of individuals without cancer. To determine if a binding agent meets this requirement, biological samples (eg, blood, serum, urine and / or tumor biopsies) from patients with and without cancer (as determined using standard clinical tests) can be tested as described in the present, by the presence of polypeptides that bind to the binding agent. It will be evident that a statistically significant number of samples with and without the disease will be tested. Each binding agent should satisfy the above criteria; however, those of ordinary skill in the art will recognize that the binding agents can be used in combination for improved sensitivity. Any agent that meets the above requirements can be a binding agent. For example, a binding agent can be a ribosome, with or without a peptide component, an RNA molecule or a polypeptide. In a preferred embodiment, a binding agent is an antibody or an antigen-binding fragment thereof. The antibodies can be prepared by any of a variety of techniques known to those of ordinary skill in the art. See, for example, Harlow and Lane, An c ibodies: A Labora tory Man ua l (Antibodies: a laboratory manual), Cold Spring Harbor Laboratory, 1988. In general, antibodies can be produced by cell culture techniques, including the generation of monoclonal antibodies as
f is described herein, or via transfection of the antibody genes in suitable bacterial or mammalian cell hosts, in order to allow the production of recombinant antibodies. In one technique, an immunogen comprising the polypeptide is injected micially into any of a wide variety of mammals (e.g., mice, rats, rabbits,
sheep or goats). In this step, the polypeptides of this invention can serve as the immunogen without modification. Alternatively, in particular for relatively short polypeptides, a superior immune response may be produced if the polypeptide is linked to a carrier protein, such as, albumin.
of bovine serum or keyhole limpet hemocyanin. The immunogen is injected into the host animal, preferably according to a predetermined schedule that incorporates one or more booster immunizations, and the animals are bled periodically. The f polyclonal antibodies specific for the polypeptide can
Then purified from such antisera by, for example, affinity chromatography using the polypeptide coupled to a suitable solid support. Monoclonal antibodies specific for an antigenic polypeptide of interest can be prepared, for example, using the
technique by Kohler and Milstein, Eur. J. Iw ~ > unol 6.511-519, 1976, and improvements thereof. Briefly, these methods involve the preparation of immortal cell lines capable of producing antibodies having the desired specificity (i.e., reactivity with the polypeptide of interest). Such cell lines can be produced, for example, from spleen cells obtained from an immunized animal as described above. Spleen cells are then immortalized by, for example, fusion with a myeloma cell fusion partner, preferably one that is syngeneic with the immunized animal. A variety of fusion techniques can be employed. For example, spleen cells and myeloma cells can be combined with a non-ionic detergent for a few minutes, and then plated at low density in a selective medium that supports the growth of hybrid cells, but not myeloma cells. A preferred selection technique uses HAT selection (hypoxanthine, aminopterin, thymidine). After. For a sufficient time, usually approximately 1 to 2 weeks, colonies of hybrids are observed. Simple colonies are selected and their culture supernatants are tested for binding activity against the polypeptide. Hybridomas are preferred having high reactivity and specificity. Monoclonal antibodies can be isolated from supernatants in growing hybridoma colonies. In addition, various techniques for enhancing performance can be employed, such as, injection of the hybridoma cell line into the peritoneal cavity of a suitable vertebrate host, such as a mouse. The monoclonal antibodies can then be collected from ascitic fluid or blood. The contaminants can be removed from the antibodies by conventional techniques, such as chromatography, gel filtration, precipitation and extraction. The polypeptides of this invention can be used in the purification process in, for example, an affinity chromatography step. Within certain embodiments, the use of antigen-binding fragments of antibodies may be preferred. Such fragments include Fab fragments, which can be prepared using standard techniques. Briefly, immunoglobulins can be purified from rabbit serum by affinity chromatography on Protein A beads columns (Harlow and Lane, An tibodies: A Labotory Manual (Antibodies: a laboratory manual) Cold Spring Harbor Laboratory, 1988) and digested by papain to produce Fab and Fc fragments. The Fab and Fc fragments can be separated by affinity chromatography on protein A-bead columns. The monoclonal antibodies of the present invention can be coupled to one or more therapeutic agents. Suitable agents in this regard include radionuclides, differentiation inducers, drugs, toxins and derivatives thereof. Preferred radionuclides include "3Y, 123I," "I, lj" l, lb6Re, "" "Re, _" "At and -1 ~ Bi. Preferred drugs include methotrexate and pyrimidine and purine analogs. Preferred include phorbol esters and butyric acid Preferred toxins include ricin, abrin, diphtheria toxin, cholera toxin, gelonin, Pseudomonas exotoxin, Shigella toxin and pokeweed antiviral protein.A therapeutic agent can be coupled (by example, covalently linked) to a suitable monoclonal antibody either directly or indirectly (for example, via a linker group) A direct reaction between an agent and an antibody is possible when each possesses a substituent capable of reacting with each other . For example, a nucleophilic group, such as an amino or sulfhydryl group, in one may be capable of reacting with a carbonyl-containing group, such as an anhydride or an acid halide, or with an alkyl group containing a good leaving group (e.g. , a halide) in the other. Alternatively, it may be desirable to couple a therapeutic agent and an antibody via a linker group. A linker group can function as a separator to distance an antibody from an agent, in order to avoid interference with binding capabilities. A linker group can also serve to increase the chemical reactivity of a substituent in an agent or an antibody, and thereby increase the coupling efficiency. An increase in chemical reactivity can also facilitate the use of agents, or functional groups in agents, which would not otherwise be possible.
It will be apparent to those skilled in the art that a variety of bifunctional or polyfunctional reagents, both homo- and hetero-functional (such as those described in the Pierce Chemical Co. catalog, Rockford, IL), can be employed, as well as the group linker. The coupling can be effected, for example, through lower groups, carboxyl groups, sulfhydryl groups or oxidized carbohydrate residues. There are numerous references describing such a methodology, for example, US Patent no. 4,671,958, 0 to Rodwell et al. Where a therapeutic agent is more potent when free from the antibody portion of the immunoconjugates of the present invention, it may be desirable to use a linker group, which is cleavable during or upon internalization in a cell. A number of different linkable linker groups has been described. Mechanisms for the intracellular release of an agent from these linker groups include cutting by reduction of a disulfide bond (e.g., U.S. Patent No. 4,489,710 to Spitler), by irradiation of a photolabile bond (e.g., U.S. Pat. No. 4,625,014), for Senter et al.), by hydrolysis of side chains of derived amino acids (e.g., U.S. Patent No. 4,638,045, to Kohn et al), by serum-mediated hydrolysis (eg, the patent US No. 4,671,958, for Rodwell et al) and acid catalyzed hydrolysis (e.g., U.S. Patent No. 4,569,789, to Blattler et al.). It may be desirable to couple more than one agent to an antibody. In one embodiment, multiple molecules of an agent are coupled to an antibody molecule. In another embodiment, more than one type of agent can be coupled to an antibody. Regardless of the particular embodiment, immunoconjugates with more than one agent can be prepared in a variety of ways. For example, more than one agent can be directly coupled to an antibody molecule, or linkers that provide multiple sites for binding can be used. Alternatively, a carrier can be used. A carrier can support the agents in a variety of ways, including covalent binding either directly or via a linker group. Suitable carriers include proteins such as albumins (e.g., U.S. Patent No. 4,507,234, for Kato et al.), Peptides and polysaccharides such as aminodextran (e.g., U.S. Patent No. 4,669,784, to Shih et al.). A carrier can also support an agent by non-covalent binding or by encapsulation, such as, within a liposome vesicle (e.g., U.S. Patents 4,429,008 and 4,873,088). Specific carriers for radionuclide agents include small radiohalogenated molecules and chelating compounds. For example, U.S. Patent No. 4,735,792 discloses representative radiohalogenated small molecules and their synthesis. A radionuclide chelate can be formed from chelating compounds that include those containing nitrogen and sulfur atoms as the donor atoms to bind the metal radionuclide, or metal oxide. For example, the US patent no. 4,673,562, for Davison et al. describes representative chelating compounds and their synthesis. A variety of administration routes can be used for antibodies and immunoconjugates. Normally, the administration will be intravenous, intramuscular, subcutaneous or in the bed of a resected tumor. It will be apparent that the precise dose of the antibody / immunoconjugate will vary depending on the antibody used, the antigen density in the tumor and the rate of evacuation of the antibody.
CELLS T The immunotherapeutic compositions also, or alternatively, may comprise T cells specific for a prostate tumor protein. Such cells can be prepared generally in vitro or ex vivo, using standard procedures. For example, T cells can be isolated from bone marrow, peripheral blood, or a fraction of bone marrow or peripheral blood of a patient, using a commercially available cell separation system, such as, the C? RATED 'system, available from CellPro Inc., Bothell WA (see also U.S. Patent No. 5,240,856; US patent no. 5,215,926; WO 89/06280; WO 91/16116 and WO 92/07243). Alternatively, T cells can be derived from cell lines or cultures of non-human, related or unrelated human mammals. T cells can be stimulated with a prostate tumor polypeptide, polynucleotide encoding a prostate tumor polypeptide and / or an antigen presenting cell (APC) that expresses such a polypeptide. Such stimulation is carried out under conditions and for a sufficient time to allow the generation of T cells that are specific for the polypeptide. Preferably, a prostate tumor polypeptide or polynucleotide is present within a delivery vehicle, such as a microsphere, to facilitate the generation of specific T cells. T cells are considered specific for a prostate tumor polypeptide if T cells kill target cells coated with the polypeptide or that express a gene encoding such a peptide. The specificity of T cells can be evaluated using any of a variety of standard techniques. For example, within a chromium release assay or proliferation assay, a stimulation index of an increase of more than two fold in lysis and / or proliferation, compared to negative controls, indicate T cell specificity. Such assays may be performed, for example, as described in Chen et al., Cancer .Res. 54: 1065-1070, 1994. Alternatively, the detection of proliferation can be detected by measuring an increased rate of DNA synthesis (e.g., by pulse-labeling T cell cultures with tritiated thymidine and measuring the amount of thymidine tritiated incorporated in DNA). Contact with a prostate tumor polypeptide (100 ng / ml - 100 μg / ml) for 3-7 days should result in at least a twofold increase in T cell proliferation. Contact as described above for 2-3 hours, it should result in the activation of T cells, as measured using standard cytokine assays, in which a two-fold increase in the level of cytokine release (eg, TNF or IFN-α) is indicative of T cell activation (see Coligan et al., Current Protocols in Immunology, Vol 1, Wiley Interscience (Greene 1998)). T cells that have been activated in response to a prostate tumor polypeptide, polynucleotide or polypeptide expressing APC, can be CD4 + and / or CD8 +. Specific T cells of prostate tumor protein can be expanded using standard techniques. Within preferred embodiments, the T cells are derived from either a patient or a related or unrelated donor, and are administered to the patient following stimulation and expansion. For therapeutic purposes, CD4 'or CD8T T cells that proliferate in response to a prostate tumor polypeptide, polynucleotide or APC, can be expanded in number either in vitro or in vivo. The proliferation of such T cells in vitro can be achieved in a variety of ways. For example, T cells can be re-exposed to a prostate tumor polypeptide, or a short peptide corresponding to an immunogenic portion of such a polypeptide, with or without the addition of T cell growth factors, such as interleukin. -2, and / or stimulator cells that synthesize a prostate tumor polypeptide. Alternatively, one or more T cells that proliferate in the presence of a prostate tumor protein can be expanded in number by cloning. Methods for cloning cells are well known in the art and include limiting dilution.
PHARMACEUTICAL COMPOSITIONS AND VACCINES Within certain aspects, the polypeptides, polynucleotides, T cells and / or binding agents described herein, may be incorporated into pharmaceutical compositions or immunogenic compositions (ie, vaccines). The pharmaceutical compositions comprise one or more such compounds and a physiologically acceptable carrier. The vaccines may comprise one or more such compounds and a non-specific immune response enhancer. A non-specific immune response enhancer can be any substance that enhances an immune response to an exogenous antigen. Examples of non-specific immune response enhancers include auxiliaries, biodegradable microspheres (e.g., polylactic galactide) and liposomes (in which the compound is incorporated, see for example, Fullerton, U.S. Patent No. 4,235,877). The preparation of vaccines is described generally in, for example, M.F. Powell and M.J. Newman, eds. "Vaccine Design (the subunit and adjuvant approach)" (Design of vaccines (the subunit and auxiliary approach)), Plenum Press (NY, 1995). Pharmaceutical compositions and vaccines within the scope of the present invention may also contain other compounds, which may be biologically active or inactive. For example, one or more immunogenic portions of other tumor antigens may be present, either incorporated in a fusion polypeptide or as a separate compound, within the composition or vaccine. A pharmaceutical composition or vaccine may contain DNA encoding one or more of the polypeptides as described above, so that the polypeptide is generated in situ. As noted above, DNA can be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacteria and viral expression systems. Numerous gene delivery techniques are well known in the art, such as those described by Rolland, Cri t. Rev. Therap. Drug Ca rrier Sys tems 15: 143-198, 1998, and references cited herein. Suitable nucleic acid expression systems contain the DNA sequences necessary for expression in the patient (such as a suitable promoter and termination signal). Bacterial delivery systems involve the administration of a bacterium (such as, Ba cillus -Calmette-Guerrin) that expresses an immunogenic portion of the polypeptide on its cell surface or secretes such an epitope. In a preferred embodiment, the DNA can be introduced using a viral expression system (e.g., vaccinia or other pustular virus, retrovirus or adenovirus), which may involve the use of a competent virus of non-pathogenic replication (defective). Suitable systems are described, for example, in Fisher-Hoch et al., Proc. Na ti. Acad. Sci. USA 86: 317-321, 1989; Flexner et al., Ann. N. Y. Acad. Sci. 569: 86-103, 1989; Flexner et al., Vacine 8: 17-21, 1990; US patents 4,603,112, 4,769,330 and 5,017,487; WO 89/01973; US patent no. 4,777,127; GB 2,200,651; EP 0,345,242; WO 91/02805; Berkner, Biotechniques 6: 616-627, 1988; Rosenfeld et al., Science 252: 431-434, 1991; Kolls et al., Proc. Na ti. Acad. Sci. USA 91: 215-219, 1994; Kass-Eisler et al., Proc. Na ti. Acad. Sci. USA 90: 11498-11502, 1993; Guzman et al., Circulation 88: 2838-2848, 1993; and Guzman et al., Cir. Res. 73: 1202-1207, 1993. Techniques for incorporating DNA into such expression systems are well known to those of ordinary skill in the art. DNA can also be "naked", as described, for example, in Ulmer et al., Science 259: 1745-1749, 1993 and reviewed by Cohen, Science 259: 1691-1692, 1993. Naked DNA uptake can increase by coating the DNA on biodegradable beads, which are transported efficiently to the cells. Although any suitable carrier known to those of ordinary skill in the art can be employed in the pharmaceutical compositions of this invention, the type of carrier will vary depending on the administration mode. The compositions of the present invention can be formulated for any suitable form of administration, including, for example, topical, oral, nasal, intravenous, intracranial, intraperitoneal, subcutaneous or intramuscular administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, a fat, a wax or a buffer. For oral administration, any of the above carriers or a solid carrier, such as mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose and magnesium carbonate can be used. Biodegradable microspheres (eg, polylactate polyglycolate) can also be employed as carriers for the pharmaceutical compositions of this invention. Suitable biodegradable microspheres are described, for example, in U.S. Pat. 4,897,268 and 5,075,109. Such compositions may also comprise buffers (e.g., neutral buffered saline or phosphate buffered saline), carbohydrates (e.g., glucose, mannose, sucrose or dextrans), mannitol, proteins, polypeptides or amino acids, such as, glycine, antioxidants. , chelating agents, such as, EDTA or glutathione, auxiliaries (for example, aluminum hydroxide) and / or preservatives. Alternatively, the compositions of the present invention can be formulated as a lyophilizate. The compounds can also be encapsulated within liposomes using well-known technology. Any of a variety of non-specific immune response enhancers can be employed in the vaccines of this invention. For example, an assistant may be included. Most auxiliaries contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as, lipid A, proteins derived from Bortadella pertussis or Mycoba cterium tuberculosis. Suitable auxiliaries are commercially available as, for example, Incomplete Auxiliary and Freund's Complete Assistant (Difco Laboratories, Detroit, MI); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ); aluminum salts, such as, aluminum hydroxide gel (alum) or aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationic or anionically derived polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and quil A.
Cytokines, such as GM-CSF or interleukin-2, -7 or -12, can also be used as auxiliaries. Within the vaccines provided herein, the auxiliary composition is preferably designed to induce a predominantly Thl-type immune response. High levels of Thl-like cytokines (eg, IFN- ?, IL-2 and IL-12) tend to favor the induction of cell-mediated immune responses to an administered antigen. In contrast, high levels of Th2-type cytokines (for example, IL-4, IL-5, IL-6, IL-10 and TNF-β) tend to favor the induction of humoral immune responses. Following the application of a vaccine as provided herein, a patient will withstand an immune response that includes Thl and Th2 type responses. Within a preferred embodiment, in which a response is predominantly Thl type, the level of Thl-type cytokines will increase to a greater degree than the level of Th2-type cytokines. The levels of these cytokines can be easily assessed using standard assays. For a review of cytokine families, see Mosmann and Coffman, Ann. Rev. Immunol. 7: 145-173, 1989. Preferred adjuncts to be used to produce a predominantly Thl-type response include, for example, a combination of monophosphoryl lipid A, preferably monophosphoryl lipid A 3-de-0-acylated (3d-MPL), together with an aluminum salt. MPL auxiliaries are available from Ribi ImmunoChem Research Inc. (Hamilton, MT; see U.S. Patent Nos. 4,436,727;
4,877,611; 4,866,034 and 4,912,094). Oligonucleotides containing CpG (in which the CpG dinucleotide is not methylated) also induce a predominantly Thl response. Such oligonucleotides are well known and are described, for example, in WO 96/02555. Another preferred aid is a saponin, preferably QS21, which can be used alone or in combination with other auxiliaries. For example, an enhanced system involves the combination of a monophosphoryl lipid A and saponin derivative, such as the combination of QS21 and 3D-MPL, as described in WO 94/00153, or a less reactogenic composition, where QS21 is quenched with cholesterol, as described in WO 96/33739. Other preferred formulations comprise an oil-in-water emulsion and tocopherol. A particularly potent auxiliary formulation involving QS21, 3D-MPL and tocopherol in an oil-in-water emulsion is described in WO 95/17210. Any vaccine provided herein may be prepared using well-known methods that result in a combination of antigen, immune response enhancer and a suitable carrier or excipient. The compositions described herein can be administered as part of a sustained release formulation (ie, a formulation such as a capsule or sponge that effects a slow release of compound following administration). Such formulations can generally be prepared using well-known technology and administered by, for example, oral, rectal or subcutaneous implantation, or by implantation at the desired target site. Sustained-release formulations may contain a polypeptide, polynucleotide or antibody dispersed in a carrier matrix and / or contained within a reservoir surrounded by a velocity-controlling membrane. The carriers for use within such formulations are biocompatible, and may also be biodegradable; preferably the formulation provides a relatively constant level of active component release. The amount of active compound contained within a sustained release formulation depends on the site of implantation, the expected rate and duration of the release and the nature of the condition to be treated or prevented. Any of a variety of delivery vehicles can be employed within pharmaceutical compositions and vaccines, to facilitate the production of an antigen-specific immune response targeting tumor cells. Delivery vehicles include antigen presenting cells (APCs), such as, dendritic cells, macrophages, B cells, monocytes and other cells that can be designed to make efficient APCs. Such cells may be, but not necessarily, genetically modified to increase the ability to present the antigen, to improve the activation and / or maintenance of the T cell response, to have anti-tumor effects per se and / or to be immunologically compatible with the receiver (ie, HLA haplotype matched). APCs can generally be isolated from any of a variety of biological fluids and organs, including tumor and peritumoral tissues, and can be autologous, allogeneic, syngeneic or xenogeneic cells. Certain preferred embodiments of the present invention use dendritic cells or progenitors thereof as antigen presenting cells. Dendritic cells are highly potent APCs (Banchereau and Steinman, Na ture 392: 245-251, 1998) and have been shown to be effective as a physiological aid to produce prophylactic or therapeutic antitumor immunity (see Timmerman and Levy, Ann. Rev. Med. 50: 507-529, 1999). In general, dendritic cells can be identified based on their normal form (starred in situ, with marked cytoplasmic processes (dendrites) visible in vitro) and based on the lack of B cell differentiation markers (CD19 and CD20), cells _T (CD3), monocytes (CD14) and natural killer cells (CD56), as determined using standard assays. Dendritic cells can be designed, of course, to express specific cell surface receptors or ligands that are not commonly found in dendritic cells in vivo or ex vivo, and such modified dendritic cells are contemplated by the present invention. As an alternative to dendritic cells, dendritic cells loaded with antigen from secreted vesicles (called exosomes) can be used within a vaccine (see Zitvogel et al., Na ture Med. 4: 594-600, 1998).
Dendritic and progenitor cells can be obtained from peripheral blood, bone marrow, cells that infiltrate the tumor, cells that infiltrate peritumoral tissues, lymph nodes, spleen, skin, umbilical cord blood or any other suitable tissue or fluid. For example, dendritic cells can be differentiated ex vivo by adding a combination of cytokines, such as GM-CSF, IL-4, IL-13 and / or TNFa to monocyte cultures harvested from peripheral blood. Alternatively, CD34 positive cells collected from peripheral blood, umbilical cord blood or bone marrow, can be differentiated into dendritic cells by adding combinations of GM-CSF, IL-3, TNFa, CD40 ligand, LPS, ligand to the culture medium. flt3 and / or other compounds that induce maturation and proliferation of dendritic cells. The dendritic cells are conveniently categorized as "immature" and "mature" cells, which allows a simple way of discrimination between two well-characterized phenotypes. However, this nomenclature should not be interpreted to exclude all possible intermediate stages of differentiation. The immature dendritic cells are characterized as APC with a high capacity for antigen uptake and processing, which correlates with the high expression of the Fc ?, receptor of mannose and marker DEC-205. The mature phenotype is usually characterized by a lower expression of these markers, but a high expression of cell surface molecules responsible for activation of T cells, such as, MHC class I and class II, adhesion molecules (e.g., CD54 and CD11 ) and costimulatory molecules (for example, CD40, CD80 and CD86). APCs can generally be transfected with a polynucleotide encoding a prostate tumor protein (or portion or other variant thereof), such that the prostate tumor polypeptide, or immunogenic portion thereof, is expressed on the cell surface . Such transfection can take place ex vivo, and a composition or vaccine comprising such transfected cells can then be used for therapeutic purposes, as described herein. Alternatively, a gene delivery vehicle that targets a dendritic cell or another antigen-presenting cell can be administered to a patient, resulting in transfection that occurs m vivo. The m vivo and ex vivo transfection of dendritic cells, for example, can be performed in a general manner using any method known in the art, such as those described in WO 97/24447, or the gene gun approach described by Mahvi et al. , Immunology and cell Biology 75: 456-460, 1997. Dendritic cell antigen loading can be achieved by incubating dendritic cells or progenitor cells with the prostate tumor polypeptide, DNA (naked or within a plasmid vector) or RNA; or with recombinant bacterium or virus s_e expresses antigen (eg, vaccinia vectors, pustular rash of domestic poultry, adenovirus or lentivirus). Prior to loading, the polypeptide can be covalently conjugated to an immunological partner that provides a T cell helper (e.g., a carrier molecule). Alternatively, a dendritic cell can be pulsed with an unconjugated immunological partner, separately or in the presence of the polypeptide.
CANCER THERAPY In additional aspects of the present invention, the compositions described herein may be used for cancer immunotherapy, such as, prostate cancer. Within such methods, the pharmaceutical compositions and vaccines are normally administered to a patient. As used herein, a "patient" refers to any warm-blooded animal, preferably a human. A patient may or may not be afflicted with cancer. Accordingly, the above pharmaceutical compositions and vaccines can be used to prevent the development of a cancer or treat a patient afflicted with a cancer. Cancer can be diagnosed using criteria generally accepted in the art, including the presence of a malignant tumor. The pharmaceutical compositions and vaccines can be administered either before or after the surgical removal of primary tumors and / or treatment, such as administration of radiotherapy or conventional chemotherapeutic drugs.
Within certain embodiments, immunotherapy can be active immunotherapy, in which the treatment is based on the in vivo stimulation of the immune system of the endogenous host to react against tumors with the administration of immune response modifying agents (such as, polypeptides and polynucleotides). described herein). Within other modalities, immunotherapy can be passive immunotherapy, in which the treatment involves the delivery of agents with established tumor immune reactivity (such as antibodies or effector cells) that can directly or indirectly mediate antitumor effects and do not necessarily depend on Immune system of the intact host. Examples of effector cells include T cells as discussed above, T lymphocytes (such as CD8 + cytotoxic T lymphocytes and lymphocytes that infiltrate tumor of CD4 + T helpers), killer cells (such as natural killer cells and killer cells activated with lymphokines). ), B cells and antigen presenting cells (such as, dendritic cells and macrophages) that express a polypeptide provided herein. T cell receptors and antibody receptors specific for the polypeptides declared herein can be cloned, expressed and transferred into other vectors or effector cells for adoptive immunotherapy. The polypeptides provided herein may also be used to generate antibodies or anti-idiotypic antibodies (such as described above and in U.S. Patent No. 4,918,164) for passive immunotherapy. Effector cells can be obtained in general f in sufficient amounts for adoptive immunotherapy in vitro growth, as described herein. Culture conditions for expanding specific effector cells from single antigen to several trillions with retention of antigen recognition in vivo are well known in the art. Such in vitro culture conditions usually use
intermittent stimulation with antigen, often in the presence of cytokines (such as, IL-2) and non-dividing feeder cells. As noted above, the immunoreactive polypeptides as provided herein can be used to rapidly expand T-cell cultures of antigen-specific, with the
to generate a number of cells for immunotherapy. In particular, antigen presenting cells, such as, dendritic, macrophages, monocytes, fibroblasts or B cells, can be pulsed with immunoreactive polypeptides or f transfected with one or more polynucleotides using techniques
standards well known in the art. For example, antigen presenting cells can be transfected with a polynucleotide having an appropriate promoter to increase expression in a recombinant virus or other expression system. Effector cells cultured for use in therapy must be capable of
grow and spread widely, and survive a long term in vivo. Studies have shown that cultured effector cells can be induced to grow in vivo and to survive a long term in numbers substantially by repeated stimulation with antigen supplemented with IL-2 (see, for example, Cheever et al., Immunological Reviews 157: 177 , 1997). Alternatively, a vector expressing a polypeptide disclosed herein can be introduced into antigen presenting cells taken from a patient and cloned ex vivo to transplant again to the same patient. The transfected cells can be reintroduced into the patient using any means known in the art, preferably in sterile form by intravenous, intracavitary, intraperitoneal or intratumor administration. The routes and frequency of administration of the therapeutic compositions described herein, as well as dosage, will vary from individual to individual, and can be easily established using standard techniques. In general, the pharmaceutical compositions and vaccines can be administered by injection (eg, intracutaneous, intramuscular, intravenous or subcutaneous), intranasally (eg, by aspiration) or orally. Preferably, between 1 and 10 doses may be administered over a period of 52 weeks. Preferably, 6 doses are administered, at 1-month intervals, and booster vaccinations may be given periodically thereafter. Alternate protocols may be appropriate for individual patients. A suitable dose is an amount of a compound which, when administered as described above, is capable of promoting an anti-tumor immune response, and is at least 10-50% above the basal level (ie, untreated) . Such a response can be monitored by measuring anti-tumor antibodies in a patient or by vaccine-dependent generation of cytolytic effector cells capable of killing the patient's tumor cells in vitro. Such vaccines should also be capable of eliciting an immune response that leads to an improved clinical outcome (e.g., more frequent remissions, complete, partial or longer disease-free survival) in vaccinated patients as compared to unvaccinated patients. In general, for pharmaceutical compositions and vaccines comprising one or more polypeptides, the amount of each polypeptide present in a dose varies from about 100 μg to 5 mg per kg of host. Suitable dose sizes will vary with the size of the patient, but will usually vary from about 0.1 ml to about 5 ml. In general, a suitable dosage and treatment regimen provides the active compound (s) in an amount sufficient to provide therapeutic and / or prophylactic benefit. Such response can be monitored by establishing an improved clinical outcome (eg, remissions plus frequencies, complete, partial or longer disease-free survival) in treated patients as compared to untreated patients. Increases in pre-existing immune responses to a prostate tumor protein generally correlate with an improved clinical outcome. Such an immune response can be evaluated in a general manner using standard proliferation, cytotoxicity or cytokine assays, which can be performed using samples obtained from a patient before and after treatment.
METHODS FOR DETECTING CANCER 10 In general, a cancer can be detected in a patient based on the presence of one or more prostate tumor proteins and / or polynucleotides that encode such proteins in a biological sample (e.g., blood, serum, urine and / or tumor biopsies) obtained from the patient. In other words, such proteins
can be used as markers to indicate the presence or absence of a cancer, such as, prostate cancer. In addition, such proteins may be useful for the detection of other cancers. The binding agents provided herein, generally allow detection of the level of antigen that binds
to the agent in the biological sample. The polynucleotide primers and probes can be used to detect the level of mRNA that encodes a protein, which is also indicative of the presence or absence of a cancer. In general, a prostate tumor sequence should be present at a level that at least
three times greater in tumor tissue than in normal tissue.
There are a variety of assay formats known to those of ordinary skill in the art to use a binding agent to detect polypeptide markers in a sample. See, for example, Harlow and Lane, Antibodies: A Labora tory Manual (Antibodies: a laboratory manual), Cold Spring Harbor
Laboratory, 1988. In general, the presence or absence of a cancer in a patient can be determined by (a) contacting a biological sample obtained from a patient with a binding agent;
(b) detecting in the sample a level of polypeptide that binds to the binding agent; and (c) comparing the polypeptide level with a predetermined cut-off value. In a preferred embodiment, the assay involves the use of immobilized binding agent on a solid support to bind to, and remove, the polypeptide from the remainder of the sample. The bound polypeptide can then be detected using a detection reagent containing a reporter group and specifically binds to the binding agent / polypeptide complex. Such detection reagents may comprise, for example, a binding agent that specifically binds to the polypeptide or an antibody or other agent that specifically binds to the binding agent, such as an anti-immunoglobulin, protein G, protein A or a lectin. Alternatively, a competitive assay may be used, in which a polypeptide is labeled with a reporter group and allowed to bind to the immobilized binding agent after incubation of the binding agent with the sample. The degree to which the components of the sample inhibit the binding of the labeled polypeptide to the binding agent is indicative of the reactivity of the sample with the immobilized binding agent. Suitable polypeptides for use within such assays include prostate tumor proteins from
full length and portions thereof, to which the binder is attached, as described above. The solid support can be any material known to those of ordinary skill in the art to which the tumor protein can bind. For example, the solid support can be
a test cavity in a microtiter plate or a nitrocellulose membrane or other suitable membrane. Alternatively, the support can be a bead or disc, such as glass, fiberglass, latex or a plastic material, such as polystyrene or polyvinyl chloride. The support can also be a particle
or a fiber optic sensor, such as those described, for example, in U.S. Pat. 5,359,681. The binding agent can be immobilized on the solid support using a variety of techniques known to those of skill in the art, which are widely described in the literature
scientific and patent. In the context of the present invention, the term "immobilization" refers to both non-covalent association, such as adsorption, and covalent attachment (which may be a direct link between the agent and functional groups on the support, or may be a link in the manner of a
crosslinking agent). Immobilization by adsorption to a cavity in a microtiter plate or to a membrane is preferred. In such cases, adsorption can be achieved by contacting the binding agent, in a suitable buffer, with the solid support for an adequate amount of time. The contact time 5 varies with temperature, but usually between 1 hour and approximately 1 day. In general, contact a cavity of a plastic microtiter plate (such as polystyrene or polyvinyl chloride) with an amount of binding agent ranging from about 10 ng to about 10 μg, and
preferably about 100 ng to about 1 μg, it is sufficient to immobilize a suitable amount of binder. The covalent binding of binding agent to a solid support can generally be achieved by first reacting the support
with a bifunctional reagent that will react both with the support and with a functional group, such as a hydroxyl or amino group, in the binder. For example, the binder can be covalently linked to supports having a polymer coating using benzoquinone or by condensation of a group
aldehyde in the support with an amine and an active hydrogen in the binding partner (see, for example, Pierce Immunotechnology Catalog and Handbook (Catalog and manual of immunotechnology), 1991 in A12-A13). In certain modalities, the test is a sandwich test
of two antibodies. This assay can be performed by first contacting an antibody that has been immobilized on a solid support, commonly the cavity of a microtiter plate, with the sample, so that the polypeptides within the sample are allowed to bind to the immobilized antibody. The unbound sample is then removed from the immobilized polypeptide-antibody complexes and a detection reagent is added.
(preferably a second antibody capable of binding to a different site in the polypeptide) containing a reporter group. The amount of detection reagent remaining attached to the solid support is then determined using a method appropriate for the specific reporter group. More specifically, once the antibody is immobilized on the support as described above, the remaining protein binding sites on the support are generally blocked. Any suitable blocking agent known to those of ordinary skill in the art, such as, bovine serum albumin or Tween 20MR (Sigma Chemical Co., St. Louis, MO). The immobilized antibody is then incubated with the sample and the polypeptide is allowed to bind to the antibody. The sample can be diluted with a suitable diluent, such as phosphate buffered saline (PBS) before incubation. In general, an appropriate contact time (i.e., incubation time) is a period that is sufficient to detect the presence of polypeptide within a sample obtained from an individual with prostate cancer. Preferably, the contact time is sufficient to achieve a binding level that is at least about 95% of that achieved in equilibrium between bound and unbound polypeptide. Those of ordinary skill in the art will recognize that the time necessary to reach equilibrium can easily be determined by testing the level of binding occurring over a period of time. At room temperature, an incubation time of approximately 30 minutes is usually sufficient. The unbound sample can be removed by washing the solid support with an appropriate buffer, such as PBS containing 0.1% Tween 20MR. The second antibody, which contains a reporter group, can then be added to the solid support. Preferred reporter groups include those groups declared above. The detection reagent is then incubated with the immobilized antibody-polypeptide complex for a sufficient amount of time to detect the bound polypeptide. An appropriate amount of time can usually be determined by testing the level of binding that occurs over a period. The unbound detection reagent is then removed and the bound detection reagent is detected using the reporter group. The method used to detect the reporting group depends on the nature of the reporting group. For radioactive groups, scintillation or auto-radiographic counting methods are generally appropriate. Spectroscopic methods can be used to detect, dyes, luminescent groups and fluorescent groups. Biotin can be detected using avidin, coupled to a different reporter group (commonly a radioactive or fluorescent group or an enzyme). Enzyme reporter groups can usually be detected by adding substrate (usually for a sufficient period), followed by spectroscopic analysis or other analysis of the reaction products. To determine the presence or absence of a cancer, such as prostate cancer, the signal detected from the reporter group that remains attached to the solid support is generally compared to a signal corresponding to a predetermined cutoff value. In a preferred embodiment, the cut-off value for the detection of a cancer is the average signal obtained when the immobilized antibody is incubated with samples from patients without cancer. In general, a sample that generates a signal that is three standard deviations above the predetermined cut-off value is considered positive for cancer. In an alternate preferred embodiment, the cut-off value is determined using a Receiver Operator Curve, according to the method of Sackett et al., Clinical Epidemiology: A Basic Science for Clinical Medicine (Clinical Epidemiology: a basic science for clinical medicine ), Littie Brown and Co. , 1985, p. 106-7. Briefly, in this modality, the cut-off value can be determined from a graph of pairs of certain positive proportions (that is, sensitivity) and false positive proportions (100% -specificity) that correspond to each of the possible values of cut for the diagnostic test result. The cutoff value on the graph that is closest to the upper left corner (that is, the value that encloses the largest area) is the most accurate cutoff value, and a sample that generates a signal that is higher than the Cut-off value determined by this method can be considered positive. Alternatively, the cut-off value can be shifted to the left along the graph to minimize the false positive proportion, or to the right, to minimize the false negative ratio. In general, a sample that generates a signal that is higher than the cutoff value determined by this method is considered positive for a cancer. In a related embodiment, the assay is performed in a strip or flow through test format, wherein the binding agent is immobilized on a membrane, such as, nitrocellulose. In the flow-through test, the polypeptides within the sample bind to the immobilized binding agent as the sample passes through the membrane. A second binding agent is then attached to the complex of binding agent-polypeptide as a solution containing the second binding agent flows through the membrane. The detection of the second bound binder can then be carried out as described above. In the strip test format, one end of the membrane to which the binder is bound is immersed in a solution containing the sample. The sample migrates along the membrane through a region containing a second binding agent and the area of immobilized binding agent. The concentration of second binding agent in the area of immobilized antibody indicates the presence of a cancer. Normally, the concentration of the second binder in the site generates a pattern, such as a line, that can be read visually. The absence of such pattern indicates a negative result. In general, the amount of immobilized binding agent
in the membrane is selected to generate a visually discernible pattern when the biological sample contains a level of polypeptide that would be sufficient to generate a positive signal in the sandwich assay of two antibodies, in the format discussed above. Preferred binding agents for use in
such assays are antibodies and antigen-binding fragments thereof. Preferably, the amount of antibody immobilized on the membrane varies from about 25 ng to about 1 μg, and more preferably from about 50 ng to about 500 ng. Such tests
can be performed normally with a very small amount of biological sample. Of course, there are numerous other assay protocols that are suitable for use with the tumor proteins or binding agents of the present invention. The previous descriptions
claim to be exemplary only. For example, it will be apparent to those of ordinary skill in the art that the above protocols can be easily modified to use prostate tumor polypeptides to detect antibodies that bind such polypeptides in a biological sample. The detection of such prostate tumor protein-specific antibodies can be correlated with the presence of a cancer. A cancer can also, or alternatively, be detected based on the presence of T cells that react specifically with a prostate tumor protein in a biological sample. Within certain methods, a biological sample comprising CD4 + and / or CD8 + cells isolated from a patient is incubated with a prostate tumor polypeptide, a polynucleotide encoding such a polypeptide and / or an APC that expresses at least an immunogenic portion of such a polypeptide, and the presence or absence of specific activation of T cells is detected. Suitable biological samples include, but are not limited to, isolated T cells. For example, T cells can be isolated from a patient by routine techniques (such as by Ficoll / Hypaque density gradient centrifugation of peripheral blood lymphocytes). T cells can be incubated in vitro for 2-9 days (usually 4 days) at 37CC with prostate tumor polypeptide (e.g., 5-25 μg / ml). It may be desirable to incubate another aliquot of a sample of T cells in the absence of prostate tumor polypeptide to serve as a control. For CD4T T cells, activation is preferably detected when evaluating the proliferation of T cells. For CD8 + T cells, activation is preferably detected when evaluating cytolytic activity. A level of proliferation that is at least twice as high and / or a level of cytolytic activity that is at least 20% higher than in disease-free patients, indicates the presence of a cancer in the patient. As noted above, a cancer can also, or alternatively, be detected based on the level of mRNA encoding a prostate tumor protein in a biological sample. For example, at least two oligonucleotide primers can be employed in a polymerase chain reaction (PCR) -based assay to amplify a portion of a prostate tumor cDNA derived from a biological sample, wherein at least one of the primers of oligonucleotides is specific to (i.e., hybridizes to) a polynucleotide that encodes the prostate tumor protein. The amplified cDNA is then separated and detected using techniques well known in the art, such as gel electrophoresis. Similarly, oligonucleotide probes that specifically hybridize to a polynucleotide encoding a prostate tumor protein can be used in a hybridization assay to detect the presence of polynucleotide encoding the tumor protein in a biological sample.
To allow hybridization under test conditions, oligonucleotide primers and probes should comprise an oligonucleotide sequence having at least about 60%, preferably at least about 75%, and most preferably at least about 90% identity to a portion of a polynucleotide that encodes a protein. prostate tumor that is at least 10 nucleotides, and preferably at least 20 nucleotides in length. Preferably, primers and / or oligonucleotide probes will hybridize to a polynucleotide that
encodes a polypeptide described herein under moderately severe conditions, as defined above. Oligonucleotide primers and / or probes that can be usefully employed in the diagnostic methods described herein, preferably are at least 10-40 nucleotides in length. In a modality
Preferred, the oligonucleotide primers comprise at least 10 contiguous nucleotides, more preferably at least 15 contiguous nucleotides, of a DNA molecule having a sequence declared in SEQ ID NO: 1-111, 115-171, 173-175, 177 , 179-305, 307-315, 326, 328, 330, 332-335, 340-375 and 381. The
Techniques for both PCR-based assays as hybridization assays are well known in the art (see, for example, Mullis et al., Cold Spring Harbor Symp. Quant. Biol., 51: 263, 1987; Erlich ed., PCR). Technology, (PCR Technology), Stockton Press, NY, 1989).
A preferred assay employs RT-PCR, in which PCR is applied in conjunction with reverse transcription. Normally, RNA is extracted from a biological sample, such as biopsy tissue, and is reverse transcribed to produce cDNA molecules. PCR amplification using at least one specific primer generates a cDNA molecule, which can be separated and visualized using, for example, gel electrophoresis. The amplification can be performed on biological samples taken from a test patient and from an individual who is not afflicted with a cancer. The amplification reaction can be performed in several dilutions of cDNA that expand by two orders of magnitude. An increase of twice or more in the expression in several dilutions of the test patient sample, as compared to the same dilutions of the non-cancerous sample, is usually considered positive. In another embodiment, the disclosed compositions can be used as markers for the progression of cancer. In this embodiment, assays as described above for the diagnosis of a cancer can be performed over time, and the change in the level of reactive polypeptide (s) or polynucleotide evaluated. For example, the tests can be carried out every 24-72 hours for a period of 6 months to 1 year, and therefore they are carried out as necessary. In general, a cancer is progressing in those patients in whom the level of polypeptide or polynucleotide detected increases with time. In contrast, the cancer is not progressing when the level of reactive polypeptide or polynucleotide either remains constant or decreases with time. Certain in vivo diagnostic tests can be performed directly on a tumor. One such assay involves contacting tumor cells with a binding agent. The bound binding agent can then be detected directly or indirectly via a reporter group. Such binding agents can also be used in histological applications. Alternatively, polynucleotide probes can be used within such applications. As noted above, to improve sensitivity, multiple prostate tumor protein markers can be assayed within a given sample. It will be apparent that specific binding agents for different proteins provided herein can be combined within a single assay. In addition, multiple primers or probes can be used concurrently. The selection of tumor protein markers can be based on routine experiments to determine combinations that result in optimal sensitivity. In addition, or alternatively, the assays for tumor proteins provided herein may be combined with assays of other known tumor antigens.
SETS D? DIAGNOSIS The present invention also provides kits for use within any of the above diagnostic methods. Such assemblies usually comprise two or more components necessary to perform a diagnostic test. The components can be composed, reagents, containers and / or equipment. For example, a container within a set may contain a monoclonal antibody or fragment thereof that specifically binds to a prostate tumor protein. Such antibodies or fragments can be provided attached to a support material, as described above. One or more additional containers may enclose elements, such as reagents or buffers, to be used in the test. Such assemblies may also, or alternatively, contain a detection reagent as described above, which contains a reporter group suitable for direct or indirect detection of antibody binding. Alternatively, a set can be designed to detect the level of mRNA encoding a prostate tumor protein in a biological sample. Such assemblies generally comprise at least one probe or oligonucleotide primer, as described above, which hybridizes to a polynucleotide encoding a protata tumor protein. Such oligonucleotide can be used, for example, within a PCR or hybridization assay. Additional components that may be present within such assemblies include a second oligonucleotide and / or a diagnostic reagent or container to facilitate the detection of a polynucleotide encoding a prostate tumor protein. The following Examples are offered by way of illustration and not by way of limitation.
EXAMPLES
EXAMPLE 1 ISOLATION AND CHARACTERIZATION OF PROSTATE TUMOR POLYPEPTIDES This Example describes the isolation of certain prostate tumor polypeptides from a prostate tumor cDNA library. A human prostate tumor cDNA expression library was constructed from poly A + RNA from prostate tumor using a Superscript Plasmid System for cDNA Synthesis and
Plasmid Cloning (BRL Life Technologies, Gaithersburg, MD 20897) following the manufacturer's protocol. Specifically, the prostate tumor tissues were homogenized with polytron (Kinematica, Switzerland) and total RNA was extracted using reagent from
Trizol (BRL Life Technologies) as directed by the manufacturer. The poly A "RNA was then purified using an oligotex spin column mRNA purification kit from Quiagen
(Qiagen, Santa Clarita, CA 91355) according to the manufacturer's protocol. The first filament cDNA was synthesized using the NotI / 01igo-dTl8 primer. Double stranded cDNA was synthesized, ligated with EcoRI / BAXI adapters (Invitrogen, San Diego, CA) and digested with Notl. Following size fractionation with Chroma Spin-1000 columns (Clontech, Palo Alto, CA), the cDNA was ligated into the EcoRI / Notl site of pCDNA3.1 (Invitrogen) and transformed into DH10B cells of E. coli ElectroMax (BRL Life Technologies) by electroporation. Using the same procedure, a normal human pancreatic cDNA expression library was prepared from a deposit of six tissue specimens (Clontech). The cDNA libraries were characterized by determining the number of independent colonies, the percentage of clones that carry the insertion, the average size of the insertion and by sequence analysis. The prostate tumor library contained 1.64 x 107 independent colonies, with 70% of the clones having an insert and the average insert size being 1745 base pairs. The normal pancreatic cDNA library contained 3.3 x 105 independent colonies, 69% of the clones having insertions and the average insert size being 1120 base pairs. For both libraries, the sequence analysis showed that most of the clones had a full-length cDNA sequence and were synthesized from mRNA, with contamination of mitochondrial DNA and minimal rRNA. The cDNA library subtraction was performed using the normal pancreatic and prostate tumor cDNA libraries, as described by Hará et al. (Blood, 84: 189-199, 1994) with some modifications. Specifically, a subtracted cDNA library specific for prostate tumor was generated as follows. The normal pancreatic cDNA library (70 μg) was digested with EcoRI, Notl and Sful, followed by a refilling reaction with Klenow fragment of DNA polymerase. After extraction with phenol-chloroform and precipitation with ethanol, the DNA was dissolved in 100 μl of H20, denatured with heat and mixed with 100 μl (100 μg) of Photoprobe biotin (Vector Laboratories, Burlingame, CA). As recommended by the manufacturer, the resulting mixture was irradiated with a 270 W solar lamp on ice for 20 minutes. Additional Photoprobe biotin (50 μl) was added and the biotinylation reaction repeated. After extraction with butanol five times, the DNA was precipitated with ethanol and dissolved in 23 μl of H20 to form the conductive DNA. To form the reporter DNA, 10 μg of prostate tumor cDNA library was digested with BamHI and XhoI, extracted with phenol chloroform and passed through Chroma spin-400 columns (Clontech). Following precipitation with ethanol, the indicator DNA was dissolved in 5 μl of H20. The indicator DNA was mixed with 15 μl of conductive DNA and 20 μ of 2 x hybridization buffer (1.5 M NaCl / 10 M EDTA / 50 mM HEPES pH 7.5 / 0.2% sodium dodecyl sulfate), covered with mineral oil and It completely denatured with heat. The sample was immediately transferred in a Maria bath at 68 ° C and incubated for 20 hours (long hybridization [LH]). The reaction mixture was then subjected to a streptavidin treatment followed by phenol / chloroform extraction. This process was repeated three times more. The subtracted DNA was precipitated, was dissolved in 12 μ of H20, mixed with 8 μl of conductive DNA and 20 μl of 2 × hybridization buffer, and subjected to hybridization at 68 ° C for 2 hours (short hybridization [SH]). After removal of biotinylated double-stranded DNA, the subtracted cDNA was ligated into the BamHI / XhoI site of chramramide-resistant pBCSK + (Stratagene, La Jolla, CA 92037) and transformed into DH10B cells of E. col i ElectroMax by electroporation to generate a subtracted cDNA library of prostate tumor (referred to as "prostate subtraction 1"). To analyze the subtracted cDNA library, the plasmid DNA was prepared from 100 independent clones, randomly chosen from the specific library of subtracted prostate tumor and grouped based on the size of the insert. Representative cDNA clones were further characterized by DNA sequencing with an Automated Sequencer Model 373A from Perkin Elmer / Applied Biosystems (Foster City, CA). Six cDNA clones, hereinafter referred to as Fl-13, Fl-12, Fl-16, Hl-1, Hl-9 and Hl-4, were abundant in the subtracted prostate-specific cDNA library. The 3 'and 5' cDNA sequences determined for Fl-12 are provided in SEQ ID NO: 2 and 3, respectively, the 3 'cDNA sequences determined for Fl-13, Fl-16, Hl-1, Hl being provided. -9 and Hl-4 in SEQ ID NO: 1 and 4-7, respectively. The cDNA sequences for the isolated clones were compared with known sequences in the gene bank using the EMBL and GenBank databases (release 96). Four of the prostate tumor cDNA clones, Fl-13, Fl-16, Hl-1 and Hl-4, were determined to encode the following previously identified proteins: prostate-specific antigen (PSA), human glandular kallikrein, gene Enhanced expression of human tumor, and mitochondrial cytochrome C oxidase subunit II. It was found that Hl-9 was identical to a previously identified human autonomous replication sequence. No significant homologies were found to the cDNA sequence for Fl-12. Subsequent studies led to the isolation of a full-length cDNA sequence for Fl-12. This sequence is provided in SEQ ID NO: 107, the corresponding predicted amino acid sequence being provided in SEQ ID NO: 108. In order to clone less abundant prostate tumor specific genes, the subtraction of the cDNA library was performed by subtracting the prostate tumor cDNA described above with the normal pancreatic cDNA library and with the three most abundant genes in the previously subtracted prostate tumor specific cDNA library: human glandular kallikrein, prostate specific antigen (PSA) and subunit II of mitochondria cytochrome C oxidase. Specifically, 1 μg of each of the human glandular kallikrein, PSA and cytochrome C oxidase subunit II cDNAs were added to the conducting DNA and the subtraction was performed as described above to provide a second subtracted cDNA library from here in hereinafter referred to as the "cDNA library specific for tumor of prostrate subtracted with spike". Twenty-two cDAN clones were isolated from the prostate tumor-specific cDNA library subtracted with spike. The 3 'and 5' cDNA sequences determined for the clones referred to as Jl-17, Ll-12, Nl-1862, Jl-13, Jl-19, Jl-25, Jl-24, Kl-58, Kl-63 , Ll-4 and Ll-14 are provided in SEQ ID NOS: 8-9, 10-11, 12-13, 14-15, 16-17, 18-19, 20-21, 22-23, 24- 25, 26-27 and 28-29, respectively. The 3 'cDNA sequences determined for the clones referred to as Jl-12, Jl-16, Jl-21, Kl-48, Kl-55, Ll-2, Ll-6, Nl-1858, Nl-1860, Nl- 1861, Nl-1864 are provided in SEQ ID NOS: 30-40, respectively. The comparison of these sequences with those in the gene bank as described above did not reveal significant homologies for three of the five most abundant DNA species., (JQ-17, Ll-12 and Nl-1862; SEQ ID NOS: 8-9, 10-11 and 12-13, respectively. Of the remaining two most abundant species, one (Jl-12; SEQ ID NO: 30) was found to be identical to the protein associated with previously identified human pulmonary surfactant, and the other (Kl-48; SEQ ID NO: 33) it was determined that it had some homology to R mRNA. norvegicus for 2-arylpropionyl-CoA epimerase. Of the 17 least abundant cDNA clones isolated from the spinal subtracted prostate tumor-specific cDNA library, four were found (Jl-16, kl-55, Ll-6 and Nl-1864; SEQ ID NOS: 31, 34, 36 and 40, respectively) were identical to sequences previously identified, it was found that two (Jl-21 and Nl-1860; SEQ ID NOS: 32 and 38, respectively) showed some homology with non-human sequences; and it was found that two (Ll-12 and Nl-1861; SEQ ID NOS: 35 and 39, respectively) showed some homology with known human sequences. No significant homologies were found to the polypeptides, Jl-13, Jl-19, Jl-24, Jl-25, Kl-58, Kl-63, Ll-4, Ll-14 (SEQ ID NOS: 14-15, 16 -17, 20-21, 18-19, 22-23, 24-25, 26-27, 28-29, respectively). Subsequent studies led to the isolation of full-length cDNA sequences for Jl-17, Kl-12 and Nl-1862 (SEQ ID NOS: 109-111, respectively). The corresponding predicted amino acid sequences are provided in SEQ ID NOS: 112-114. Ll-12 is also referred to as P501S. In a further experiment, four additional clones were identified by subtracting a prostate tumor cDNA library with normal prostate cDNA prepared from a deposit of three poly A + normal prostate RNA (referred to as "prostate subtraction 2"). The cDNA sequences determined for these clones, hereinafter referred to as Ul-3064, Ul-3065, VI-3692 and 1A-3905, are provided in SEQ ID NO: 69-72, respectively. The comparison of the determined sequences with those in the gene bank did not reveal significant homologies to Ul-3065. A second spike subtraction (referred to as "prostate subtraction spike 2") was performed by subtracting a prostate tumor-specific cDNA library with spike with normal pancreatic cDNA library and additionally spiked with PSA, Jl-17, protein associated with pulmonary surfactant, mitochondrial DNA, cytochrome c oxidase subunit II, Nl-1862, autonomous replication sequence, Ll-12 and enhanced gene of tumor expression. Four additional clones were isolated, hereinafter referred to as Vl-3686, Rl-2330, 1B-3976 and Vl-3679. The cDNA sequences determined for these clones are provided in SEQ ID NO: 73-76, respectively. The comparison of these sequences with those in the gene bank did not reveal significant homologies for Vl-3686 and Rl-2330. Further analysis of the three prostate subtractions described above (prostate subtraction 2, specific cDNA library subtracted from prostate tumor with spike, and prostate subtraction spike 2), resulted in the identification of sixteen additional clones, referred to as 1G- 4736, 1G-4738, 1G-4741, 1G-4744, 1G-4734, 1H-4774, 1H-4781, 1H-4785, 1H-4787, 1H-4796, 11-4810, 11-4811, 1J-4876, 1K-4884 and 1K-4896. The cDNA sequences determined for these clones are provided in SEQ ID NOS: 77-92, respectively. Comparison of these sequences with those in the gene bank as described above did not reveal significant homologies to 1G-4741, 1G-4734, 11-4807, 1J-4876 and 1K-4896 (SEQ ID NOS: 79, 81, 87, 90 and 92, respectively). Additional analysis of the isolated clones led to the determination of prolonged cDNA sequences for 1G-4736, 1G-4738, 1G-4741, 1G-4744, 1H-4774, 1H-4781, 1H-4785, 1H-4787, 1H- 4796, 11-4807, 1J-4876, 1K-4884 and 1K-4896, provided in SEQ ID NOS: 179-188 and 191-193, respectively, and to the determination of additional partial cDNA sequences for 11-4810 and 11- 4811, provided in SEQ ID NOS: 189 and 190, respectively. Additional studies with prostate subtraction pin 2, resulted in the isolation of three more clones. Their sequences were determined as described above and compared with the most recent GenBank. The three clones were found to have homology with known genes, which are cysteine rich protein, KIAA0242 and K1AA0280 (SEQ ID NO: 317, 319 and 320, respectively). Additional analysis of these clones by Synteni microarray (Synteni, Palo Alto, CA) showed that all three clones were overexpressed in most of the prostate and prostate BPH tumors, as well as in the majority of normal prostate tissues tested, but there was low expression in the other normal tissues.
An additional subtraction was performed by subtracting a normal prostate cDNA library with normal pancreatic cDNA (referred to as "prostate subtraction 3"). This led to the identification of six additional clones referred to as 1G-4761, 1G-4762, 1H-4766, 1H-4770, 1H-4771 and 1H-4772 (SEQ ID NOS: 93-98). The comparison of these sequences with those in the gene bank did not reveal significant homologies to 1G-4761 and 1H-4771 (SEQ ID NOS: 93 and 97, respectively). Further analysis of the isolated clones led to the determination of extended cDNA sequences for 1G-4761, 1G-4762, 1H-4766 and 1H-4772 provided in SEQ ID NOS: 194-196 and 199, respectively, and to the sequence determination of additional partial cDNAs for 1H-4770 and 1H-4771, provided in SEQ ID NOS: 197 and 198, respectively. Subtraction of a prostate tumor cDNA library, prepared from a poly A + RNA deposit of three prostate cancer patients, with normal pancreatic cDNA library (prostate subtraction 4) led to the identification of eight clones , referred to as 1D-4297, 1D-4309, ID.1-4278, ID-4288, ID-4283, ID-4304, ID-4296 and ID-4280 (SEQ ID NOS: 99-107). These sequences were compared with those in the gene bank as described above. No significant homologies were found at 1D-4283 and 1D-4304 (SEQ ID NOS: 103 and 104, respectively). Further analysis of the isolated clones led to the determination of extended cDNA sequences for 1D-4309, ID.1-4278, 1D-4288, 1D-4283, 1D-4304, 1D-4296 and 1D-4280, provided in SEQ ID NOS: 200-206, respectively. The cDNA clones isolated in prostate subtraction 1 and prostate subtraction 2, described above, were amplified by colony PCR and their levels of mRNA expression were determined in prostate tumor, normal prostate and in various other normal tissues using technology of microarray (Synteni, Palo Alto, CA). Briefly, the PCR amplification products were dotted on slides in an array format, when each product had a unique location in the array. MRNA was extracted from the tissue sample to be tested, reverse transcribed and fluorescent-labeled cDNA probes were generated. The microarrays were probed with the labeled cDNA probes, the slides were scanned and the fluorescence intensity was measured. This intensity correlates with the intensity of hybridization. It was found that two clones (referred to as P509S and P510S) were overexpressed in normal prostate and prostate tumor and expressed at low levels in all other normal tissues tested (liver, pancreas, skin, bone marrow, brain, breast, adrenal gland, bladder, testes, salivary gland, large intestine, kidney, ovary, lung, spinal cord, skeletal muscle and colon). The cDNA sequences determined for P509S and P510S are provided in SEQ ID NO: 223 and 224, respectively. The comparison of these sequences with those in the gene bank as described above, revealed some homology with previously identified ESTs.
Additional studies led to the isolation of the full-length cDNA sequence for P509S. This sequence is provided in SEQ ID NO: 332 with the corresponding predicted amino acid sequence being provided in SEQ ID NO:
339.
EXAMPLE 2 DETERMINATION OF TISSUE SPECIFICITY OF
PROSTATE TUMOR POLYPEPTIDES Using gene-specific primers, the mRNA expression levels were examined for the representative prostate tumor polypeptides Fl-16, Hl-1, Jl-17 (also referred to as P502S), Ll-12 (also referred to as P501S), Fl-12 (also referred to as P504S) and Nl-1862 (also referred to as P503S), in a variety of normal and tumor tissues using RT-PCR. Briefly, total RNA was extracted from a variety of normal and tumor tissues using Trizol reagent as described above. First strand synthesis was performed using 1-2 μg of total RNA with SuperScript II reverse transcriptase (BRL Life Technologies) at 42 ° C for one hour. The cDNA was then amplified by PCR with gene-specific primers. To ensure the semi-quantitative nature of RT-PCR, β-actin was used as an internal control for each of the tissues examined.
First, serial dilutions of the first-strand cDNAs were prepared and RT-PCR assays were performed using β-actin specific primers. A dilution was then chosen that would allow the linear range amplification of the β-actin template and be sufficiently sensitive to reflect the differences in the initial copy numbers. Using these conditions, β-actin levels were determined for each reverse transcription reaction of each tissue. DNA contamination was minimized by challenge with DNase and by ensuring a negative PCR result when using the first filament cDNA that was prepared without adding reverse transcriptase. The levels of mRNA expression were examined in four different types of tumor tissue (prostate tumor from 2 patients, breast tumor from 3 patients, colon tumor, lung tumor), and sixteen different normal tissues, including prostate, colon , kidney, liver, lung, ovary, pancreas, skeletal muscle, skin, stomach, testes, bone marrow and brain. It was found that Fl-16 was expressed at high levels in prostate tumor tissue, colon and normal prostate tumor, and at lower levels in liver, skin and normal tests, without being detectable in the other tissues examined. It was found that Hl-1 was expressed at high levels in prostate tumor, lung tumor, breast tumor, normal prostate, normal colon and brain ormaI, at much lower levels in lung, pancreas, skeletal muscle, skin, small intestine, normal bone marrow, and was not detected in the other tissues tested. Jl-17 (P502S) and Ll-12
(P501S) appear to be overexpressed specifically in the prostate, both genes being expressed at high tumor levels
of prostate and normal prostate, but at low to not detectable levels in all other tissues examined. It was found that Nl-1862 (P503S) was overexpressed in 60% of prostate tumors and was detectable in normal colon and kidney. The results of RT-PCR indicate, in this way, that Fl-16, Hl-1, Jl-10 17 (P502S), Nl-1862 (P503) and Ll-12 (P501S) are either prostate-specific or are expressed at significantly elevated levels in the prostate. Additional RT-PCR studies showed that Fl-12 (P504S) is over-expressed in 60% of prostate tumors, detectable in
Kidney normal but not detectable in all other tissues tested. Similarly, it was shown that Rl-2330 was overexpressed in 40% of prostate tumors, was detectable in kidney and normal liver, but was not detectable in all other tissues tested. It was found that Ul-3064 was overexpressed in 60% of
prostate tumors, and was also expressed in breast and colon tumors, but was not detectable in normal tissues. The characterization of RT-PCR of Rl-2330, Ul-3064 and 1D-4279 showed that these three antigens are overexpressed in prostate and / or prostate tumors.
Northern analysis with four prostate tumors, two normal prostate samples, two BPH prostates and normal colon, kidney, liver, lung, pancreas, skeletal muscle, brain, stomach, testes, small intestine and bone marrow showed that Ll-12 (P501S) is over-expressed in normal prostate and prostate tumors, while not being detectable in other normal tissues tested. Jl-17 (P502S) was detected in two prostate tumors and not in the other tissues tested. It was found that Nl-1862 (P503S) was over-expressed in three prostate tumors and to be expressed in normal prostate, colon and kidney, but not in the other tissues tested. It was found that Fl-12 (P504S) is highly expressed in two prostate tumors and is not detectable "in all other tissues tested." The microarray technology described above was used to determine the expression levels of representative antigens described herein. in prostate tumor, breast tumor and the following normal tissues: prostate, liver, pancreas, skin, bone marrow, brain, chest, adrenal gland, bladder, testes, salivary gland, large intestine, kidney, ovary, lung, spinal cord, skeletal muscle and colon. It was found that Ll-12 (P501S) was over-expressed in normal prostate and prostate tumor, detecting some expression in normal skeletal muscle. It was found that both Jl-12 and Fl-12 (P504S) were over-expressed in prostate tumor, the expression being lower or undetectable in all other tissues tested. It was found that Nl-1862 (P503S) was expressed at high levels in normal prostate and prostate tumor, and at low levels in normal large bowel and normal colon, with no detectable expression in all other tissues tested. It was found that Rl-2330 was overexpressed in normal prostate and prostate tumor, and expressed at lower levels in all other tissues tested. It was found that 1D-4279 was over-expressed in normal prostate and prostate tumor, expressed at lower levels in normal spinal cord and was not detectable in all other tissues tested. An additional microarray analysis to specifically resolve the extent to which P501S (SEQ ID NO: 110) was expressed in breast tumor, revealed moderate overexpression not only in breast tumor, but also in metastatic breast tumor (2 / 31), with negligible expression at low in normal tissues. These data suggest that P501S can be overexpressed in several breast tumors as well as in prostate tumors. The expression levels of 32 ESTs (expressed sequence tags) described by Vasmatizis et al. (Proc. Na ti. Acad. Sci. USA 95: 300-304, 1998) in a variety of normal tumors and tissues, were examined by microarray technology as described above. It was found that two of these clones (referred to as P1000C and P1001C) were overexpressed in prostate and normal prostate tumor, and were expressed at low to not detectable levels in all other tissues tested (aorta, thymus, PBMC at rest and activated, epithelial cells, spinal cord, adrenal gland, fetal tissues, skin, salivary gland, large intestine, bone marrow, liver, lung, dendritic cells, stomach, lymph nodes, brain, heart, { ^^ small intestine, muscle Skeletal, colon and kidney The 5 cDNA sequences determined for P1000C and P1001C are provided in SEQ ID NO: 384 and 472, respectively .. The P1001C sequence was found to show some homology to the human mRNA previously isolated for the JM27 protein. significant homologies were found to the P1000C sequence 10 The expression of the polypeptide encoded by the full-length cDNA sequence for Fl-12 (also referred to as P504S; SEQ ID NO: 108) was investigated by immunohistochemical analysis. Rabbit anti-P504S polyclonal antibodies were generated against the full-length P504S protein
using standard techniques. The subsequent isolation and characterization of the polyclonal antibodies were also performed by techniques well known in the art. Immuno-isotoxic analysis showed that the P504S polypeptide was expressed in 100% of prostate carcinoma samples tested
(n = 5). The polyclonal rabbit anti-P504S antibody did not appear to mark benign prostate cells with the same granular cytoplasmic staining, but with clear nuclear staining. Normal tissue analysis revealed that the encoded polypeptide was
23 Exoresado in some, but not in all normal human tissues. Positive cytoplasmic staining with rabbit anti-P504S polyclonal antibody was found in human, normal lung, colon, brain, liver and kidney-associated macrophages, while the heart and bone marrow were negative. These data indicate that the P504S polypeptide is present in prostate cancer tissues, and that they are qualitative and quantitative differences in spotting between benign prostatic hyperplasia tissues and prostate cancer tissues, suggesting that this polypeptide can be selectively detected in tumors of the prostate. prostate and therefore, are useful in the diagnosis of prostate cancer.
EXAMPLE 3 ISOLATION AND CHARACTERIZATION OF PROSTATE TUMOR POLYPEPTIDES
THROUGH SUBSTRACTION BASED ON PCR A cDNA subtraction library, containing normal prostate cDNA subtracted with ten other normal tissue cDNAs (brain, heart, kidney, liver, lung, ovary, placenta, skeletal muscle, spleen and thymus) and then subjected to a first round of PCR amplification, it was purchased from Clontech.
This library underwent a second round of amplification of
PCR, following the manufacturer's protocol. The resulting cDNA fragments were subcloned into the vector pT7 Blue T-vector (Novagen, Madison, Wl) and transformed into E. col i XL-1 Blue MRF (Stratagene). DNA was isolated from independent clones and sequenced using an Automated Sequencer Model 373A from Perkin Elmer / Applied Biosystems Division. Fifty-nine positive clones were sequenced. Comparison of the DNA sequences of these clones with those in the gene bank, as described above, revealed no significant homologies for 25 of these clones, hereinafter referred to as P5, P8, P9, P18, P20, P30 , P34, P36, P38, P39, P42, P50, P53, P55, P60, P64, P65, P73, P75, P76, P79 and P84. The cDNA sequences determined for these clones are provided in SEQ ID NO: 41-45, 47-52 and 54-65, respectively. It was found that P29, P47, P68 and P82 (SEQ ID NO: 46, 53 and 66-68, respectively) show some degree of homology with previously identified DNA sequences. As far as the inventors are aware, none of these sequences has previously been shown to be present in the prostate. Additional studies using the PCR-based methodology described above, resulted in the isolation of more than 180 additional clones, of which 23 were found not to show significant homologies to known sequences. The cDNA sequences determined for these clones are provided in SEQ ID NOs: 115-123, 127, 131, 137, 145, 147-151, 153, 156-158 and 160. Twenty-three clones were found (SEQ ID NO: 124 -126, 128-130, 132-136, 138-144, 146, 152, 154, 155 and 159) show some homology to ESTs previously identified. It was found that about ten more clones (SEQ ID NO: 161-170) have some degree of homology with known genes. The larger cDNA clones containing the P20 sequence represent splice variants of a gene referred to as P703P. The DNA sequence determined for the variants referred to as DE1, DE13 and DE14 are provided in SEQ ID NOS: 171, 175 and 177, respectively, the corresponding predicted amino acid sequences being provided in SEQ ID NO: 172, 176 and 178, respectively. The cDNA sequence determined for an extended spliced form of P703 is provided in SEQ ID NO: 225. The DNA sequences for the splice variants referred to as DE2 and DE6 are provided in SEQ ID NOS: 173 and 174, respectively. The levels of mRNA expression for representative clones in tumor tissues (prostate (n = 5), breast (n = 2), colon and lung), normal tissues (prostate (n = 5), colon, kidney, liver, lung (n = 2), ovary (n = 2), skeletal muscle, skin, stomach, small intestine and brain), and activated and non-activated PBMC were determined by RT-PCR, as described above. The expression in a sample of each type of tissue was examined unless otherwise indicated. It was found that P9 was highly expressed in normal prostate and prostate tumor compared to all normal tissues except normal colon, which showed comparable expression. It was found that P20, a portion of the P703P gene, was highly expressed in normal prostate and prostate tumor, compared to the twelve normal tissues tested. A modest increase in P20 expression was observed in breast tumor (n = 2), colon tumor and lung tumor, compared with all normal tissues except lung (1 of 2). Increased expression of P18 was found in normal prostate, prostate tumor and breast tumor, compared with other normal tissues, except lung and stomach. A modest increase in P5 expression in normal prostate was observed, compared to most others
normal tissues. However, some elevated f expression was observed in normal lung and PBMC. Elevated expression of P5 was also observed in prostate tumors (2 of 5), breast tumor and a lung tumor sample. For P30, similar expression levels seen in normal prostate and prostate tumor,
compared with six of twelve other normal tissues tested. Increased expression was observed in breast tumors, a lung tumor sample and a colon tumor sample, and also in normal PBMC. It was found that P20 was overexpressed in prostate tumor (5 of 5) and normal prostate (5 of 5), compared with the
most normal tissues. However, substantial expression of P29 was observed in normal colon and normal lung (2 of 2). It was found that P80 was overexpressed in prostate tumor (5 of 5) and normal prostate (5 of 5), compared with all other normal tissues tested, with an increased expression observed
in colon tumor.
Additional studies resulted in the isolation of twelve additional clones, hereinafter referred to as 10-d8, 10-hlO, ll-c8, 7-g6, 8-b5, 8-b6, 8-d4, 8-d9, 8 -g3, 8-hll, 9-fl2 and 9-f3. The DNA sequences determined for 10-d8, 10-hl0, ll-c8, 8-d4, 8d-9, 8-hll, 9-fl2 and 9-f3 are provided in SEQ ID NO: 207, 208, 209, 216, 217, 220, 221 and 222, respectively. The forward and backward DNA sequences determined for 7-g6, 8-b5, 8-b6 and 8-g3 are provided in SEQ ID NO: 210 and 211; 212 and 213; 214 and 215; and 218 and 219, respectively. The comparison of these sequences with those in the gene bank did not reveal significant homologies to the sequence of 9-f3. It was found that clones 10-d8, ll-c8 and 8-hll show some homology to previously isolated ESTs, whereas 10-hl0, 8-b5, 8-b6, 8-d4, 8-d9, 8-g3 and 9-fl2 show some homology to previously identified people. The additional characterization of 7-G6 and 8-G3 showed identity to the known PAP and PSA genes, respectively. The levels of mRNA expression for these clones determined using the micro-array technology described above. It was found that the clones 7-G6, 8-G3, 8-B5, 8-B6, 8-D4, 8-D9, 9-F3, -F12, 9-H3, 10-A2, 10-A4, 11- C9 and 11-F2 are overexpressed in normal prostate and prostate tumor, with low or undetectable expression in other tissues tested. An increased expression of 8-F11 was observed in prostate tumor and normal prostate, veg, skeletal muscle and colon. An increased expression of 10-H10 was observed in prostate tumor and normal prostate, bladder, lung, colon, brain and large intestine. Increased expression of 9-B1 was observed in prostate tumor, normal breast and prostate tumor, salivary gland, large intestine and skin, with increased expression of 11-C8 in prostate tumor, and normal prostate and large intestine. It was found that an additional cDNA fragment derived from the normal prostate subtraction based on PCR, described above, was prostate specific by both micro-array technology and RT-PCR. The cDNA sequence determined from this clone (referred to as 9-A11) is provided in SEQ ID NO: 226). The comparison of this sequence with those in the public databases revealed 99% identity with the known gene HOXB13. Additional studies led to the isolation of clones 8-C6 and 8-H7. The cDNA sequences determined for these clones are provided in SEQ ID NO: 227 and 228, respectively. It was found that these sequences show some homology to previously isolated ESTs. Methodologies based on PCR and hybridization used to obtain longer cDNA sequences for clone P20 (also referred to as P703P), producing three additional cDNA fragments that progressively extend to the 5 'end of the gene. These fragments, referred to as P703PDE5, P703P6.26 and P703PX-23 (SEQ ID NO: 326, 328 and 330, the corresponding amino acid sequences predicted in SEQ ID NO: 327 being provided), 329 and 331, respectively), contain the additional 5 'sequence. P703PDE5 was recovered by sorting a cDNA library (# 141-26) with a portion of P703P as a probe. P703P6.26 was recovered from a mixture of three prostate tumor cDNAs and P703PX_23 was recovered from the cDNA library (# 438-48). Together, the additional sequences include all putative mature serine protease together with part of the putative signal sequence. Additional studies using a PCR-based subtraction library of a prostrate tumor deposit subtracted against a noradial tissue deposit (referred to as JP: PCR subtraction), resulted in the isolation of thirteen additional clones, seven of which do not share any Significant homology to known GenBank sequences. The cDNA sequences determined for these seven clones (P711P, P712P, new 23, P774P, P775P, P710P and P768P) are provided in SEQ ID NO: 307-311, 313 and 315, respectively. The remaining six clones (SEQ ID NO: 316 and 321-325) show sharing some homology to known genes. By microarray analysis, the thirteen clones showed overexpression three or more times in prostate tissues, including prostate tumors, BPH and normal prostate, as compared to normal non-prostate tissues. Clones P711P, P712P, 23 new and P768P show overexpression in the majority of prostate tumors and BPH tissues tested (n = 29) and in most normal prostate tissues (n = 4), but expression levels from background to low in all normal tissues. Clones P774P, P775P and P710P showed comparatively lower expression and expression in a few prostate tumors and BPH samples, with negative expression at low in normal prostate. f The full-length cDNA for P711P was obtained by using the partial sequence of SEQ ID NO: 307 to classify a prostate cDNA library. Specifically, a directionally cloned prostate cDNA library was prepared using standard techniques. One million colonies of this library were plated on LB / Amp plates. Membrane filters were used
nuylon to lift these colonies, and the cDNAs that were chosen by these filters were denatured and cross-linked to the filters by UV light. The P711P cDNA fragment of SEQ ID NO: 307 was radio-labeled and used to hybridize with these filters. Positive clones were selected and
prepared cDNAs and sequenced using an automatic Perkin Elmer / Applied Biosystems sequencer. The determined full-length sequence of P711P is provided in SEQ ID NO: 382, the corresponding predicted amino acid sequence being provided in SEQ ID NO: 383. Using PCR-based hybridization methodologies, an additional cDNA sequence information was derived of two clones described above, 11-C9 and 9-F3, hereinafter referred to as P707P and P714P, respectively (SEQ ID NO: 333 and 334). After a comparison with the most recent GenBank, it was found that P707P is a splicing variant of the known HoxBl3 gene. In contrast, no significant homologies were found to P714P. Clones 8-B3, P89, P98, P130 and P201 (as described in US Patent Application No. 09 / 020,956, filed on February 9, 1998) contained within a contiguous sequence, referred to as P705P (SEQ), were found. ID NO: 335, with the predicted amino acid sequence provided in SEQ ID NO: 336), which was determined to be a splice variant of the known NKX 3.1 gene.
EXAMPLE 4 SYNTHESIS OF POLYPEPTIDES Polypeptides can be synthesized in a peptide synthesizer from Perkin Elmer / Applied Biosystems 430A using FMOC chemistry with activation of HPTU (O-benzotriazole-N, N ', N' -tetramethyluronium hexafluorophosphate). A Gly-Cys-Gly sequence can be used at the amino terminus of the peptide, to provide a method of conjugation, binding to an immobilized, or labeled surface of the peptide. The cutting of the peptides from the solid support can be carried out using the following cutting mixture: trifluoroacetic acid: ethanedithiol: thioanisole: water -.phenol (40: 1: 2: 2: 3). After cutting for 2 hours, the peptides can be priced in cold methyl-t-butyl ether. The peptide pellets can then be dissolved in water containing 0.1% tpfluoroacetic acid (TFA) and lyophilized before purification by reverse phase HPLC of C18. A gradient of 0% -60% acetonitoplo (containing 0.1% TFA) in water (containing 0.1% TFA) can be used to levigate the peptides. Following the freeze-drying of the pure fractions, the peptides can be characterized using electroatomization or other types of mass spectrometry and by amino acid analysis.
EXAMPLE 5 ADDITIONAL ISOLATION AND CHARACTERIZATION OF TUMOR POLYPEPTIDES
PROSTATE 10 THROUGH PCR-BASED SUBSTRACTION A cDNA library generated from primary prostate tumor mRNA as described above was subtracted with normal prostate cDNA. The subtraction was done using a PCR-based protocol (Clontech), which was modified to generate more fragments
large. Within this protocol, double-strand drive and tester cDNA were digested with five restriction enzymes recognizing six nucleotide restriction sites (Mlul, Mscl, PvuII, SalI and Stul). This digestion resulted in an average cDNA size of 600 op (base pairs),
instead of the average size of 300 bp that results from digestion with Rsal according to the Clontech protocol. This modification did not affect the efficiency of subtraction. Then two tester populations were created with different adapters, and the impetitor library remained without aaaptaaores. The impeller and tester libraries were then hybridized using excess driving cDNA. In the first step of hybridization, the impeller was hybridized separately with each of the two populations of cDNA tester. This resulted in populations of (a) testers without hibpdar, (b) tester cDNAs hybridized to other tester cDNAs, (c) tester cDNAs hybridized to cDNAs, and (d) unhybridized cDNAs. The two separate hybridization reactions were then combined, and rehybridized in the presence of cDNA
additional denatured impeller. Following this second hybridization, in addition to populations (a) to (d), a fifth population was generated, in which the cDNA tester with an adapter hybridized to cDNA tester with the second adapter. Accordingly, the second step of hybridization resulted in
enrichment of differentially expressed sequences, which could be used as templates for PCR amplification with specific adapter primers. The ends were then filled, and PCR amplification was performed using specific adapter primers.
Only the population (e), which contained cDNA tester that did not hybridize to the driving cDNA, was amplified exponentially. A second step of PCR amplification was then performed, to reduce the background and further enrich the expressed sequences of ii-iera Differential This PCR-based subtraction technique normalizes the differentially expressed cDNAs, so that the rare transcripts that are overexpressed in prostate tumor tissue may be recoverable. Such transcripts would be difficult to recover by traditional subtraction methods. In addition to genes known to be overexpressed in prostate tumor, seventy-seven other clones were identified. Sequences of these partial cDNAs are provided in SEQ ID NO: 29 to 305. Most of these clones did not have significant homology to database sequences. The exceptions were JPTPN23 (SEQ ID NO: 231, similarity to protein containing pig valosm), JPTPN30 (SEQ ID NO: 234, similarity to rat mRNA for proteasome subunit), JPTPN45 (SEQ ID NO: 243, similarity to isocitrate dehydrogenase dependent on rat cytosolic NADP norvegicus), JPTPN46 (SEQ ID NO: 244, similarity to DNA sequence H8 4 d4 of human subclone), JP1D6 (SEQ ID NO: 265, similarity to light chain A of dinein G. gallus ), JP8D6 (SEQ ID NO: 288, similarity to human BAC clone RG016J04), JP8F5 (SEQ ID NO: 289, similarity to DNA sequence H8 3 b5 of human subclone), and JP8E9 (SEQ ID NO: 299; human Alu sequence). Additional studies using the PCR-based subtraction library consisting of a prostrate tumor reservoir subtracted against a normal prostate reservoir (referred to as a subtraction of PT-PN) produced three additional clones.
Comparison of the cDNA sequences of these clones with the more recent release of GenBank did not reveal significant homologies to the two clones referred to as P715P and P767P (SEQ ID NO: 312 and 314). It was found that the remaining clone shows some homology to the known gene KIAA0056 (SEQ ID NO: 318). Using microarray analysis to measure the levels of mRNA expression in various tissues, the three clones were found to be overexpressed in prostate tumors and BPH tissues. Specifically, clone P715P was over-expressed in most
of prostate tumors and BPH tissues by a factor of three or greater, with high expression observed in the majority of normal prostate samples and in fetal tissue, but negative to low expression in all other normal tissues. The clone P767P was over-expressed in several prostate tumors and tissues
BPH, with moderate expression levels in half of normal prostate samples, and background to low expression in all other normal tissues tested. Additional analysis, by microarray as described above, of the PT-PN PCR subtraction library and a library
subtraction of DNA containing prostrate tumor cDNA subtracted with a deposit of normal tissue cDNAs, led to the isolation of 27 additional clones (SEQ ID NO: 340-365 and 381), which were determined to be overexpressed in prostate tumor It was found that the clones of SEQ ID NO: 341, 342, 345,
347, 348, 349, 351, 355-359, 361, 362 and 364 are also expressed in normal prostate. It was found that the expression of the 26 clones in a normal tissue varedad was low or not detectable, with the exception of P544S (SEQ ID NO: 356), which was expressed in the small intestine. Of the 26 clones, 10 (SEQ ID NO: 340-349) showed some homology to previously identified sequences. No significant homologies were found to the clones of SEQ ID NO. 350-365.
EXAMPLE 6 10 INITIATION OF MICE PEPTIDE AND PROPAGATION OF CTL LINES 6.1. This example illustrates the preparation of a CTL cell line for celias expressing the P502S gene. Mice expressing the transgene for HLA were immunized
Human A2.1 (provided by Dr L. Sherman, The Scripps
Research Institute, La Jolla, CA), with peptide P2S # 12 (VLGWVAEL;
SEQ ID NO: 306), which is derived from the P502S gene (also referred to herein as Jl-17, SEQ ID NO: 8), as described by Theobald et al., Proc. Na ti. Acad. Sci. USA 92: 11993-2011 11997, 1995 with the following modifications. Mice were immunized with 100 μg of P2S # 12 and 120 μg of an I-Ab binding peptide derived from hepatitis B virus protein emulsified in incomplete Freund's adjuvant. Three weeks later, these mice were sacrificed and cell suspensions were prepared
simple using a naylon mesh. The cells were then resuspended in 6 x 106 cells / ml in complete medium (RPMI-1640, Gibco BRL, Gaithersburg, MD) containing 10% FCS, 2mM glutamine (Gibco BRL), sodium pyruvate (Gibco BRL), non-essential amino acids (Gibco BRL), 2 x 10"5 M 2-mercaptoethanol, 50U / ml penicillin and streptomycin, and were cultured in the presence of LPS blasts (transgenic A2 spleen cells cultured in the presence of 7μg / ml dextran sulfate). and 25 μg / ml of LPS for 3 days), P2S # 12-pulsed (5 mg / ml of P2S # 12 and 10 mg / ml of β2-microglobulin) irradiated (3000 rads). Six days later, they were re-stimulated cells (5 x 10 5 / ml) with 2.5 x 10 6 / ml of EL4A2Kb cells pulsed by peptide, irradiated (20,000 rads) (Sherman et al., Science 258: 815-818, 1992) and 3 x 10 6 / ml of cells A2 transgenic spleen feeders Cells were cultured in the presence of 20U / ml of 11-2 cells were continued re-stimulating on a weekly basis as described, in preparation n for cloning the line. The P2S # 12 line was cloned by limiting dilution analysis with EL4 A2Kb tumor cells pulsed by peptide (1 x 10 4 cells / well) as stimulants and transgenic A2 spleen cells as feeders (5 x 10 5 cells / well) grown in the presence of 30U / ml of IL-2. On day 14, the cells were re-stimulated as before. On day 21, the clones that were grown were isolated and kept in culture. Several of these clones demonstrated significantly higher reactivity (lysis) against human fibroblasts (expressing HLA A2.1) transduced with P502S, than against control fibroblasts. An example is presented in Figure 1. These data indicate that P2S # 12 represents a naturally processed epitope of the P502S protein, which is expressed in the context of the human HLA A2.1 molecule.
6. 2. This example illustrates the preparation of murine CTL lines and CTL clones specific for cells expressing the P501S gene. 10 This series of experiments was performed in a manner similar to that described above. Mice were immunized with the peptide PlS # 10 (SEQ ID NO: 337), which is derived from the P501S gene (also referred to herein as 11-12, SEQ ID NO 110). Peptide P1S # 10 was derived by analysis of the predicted polypeptide sequence
for P501S for potential HLA-A2 binding sequences as defined by published HLA-A2 binding motifs (Parker, KC, et al, J. Immunol., 152: 163, 1994). Peptide P1S # 10 was synthesized as described in Example 4, and empirically tested for HLA-A2 binding using a competition assay based on T cells.
tested A2 peptides predicted for their ability to compete for the presentation of specific peptide HLA-A2 to a CTL clone restricted by HLA-A2 (D150M58), which is specific for the HLA-A2 influenza influenza matrix peptide fluM58. D150M58 CTL secretes TNF in response to self-presentation of peptide
fluM58. In the competition assay, the test páptidos in 100-200 μg / ml were added to cultures of D150M58 CTL, in order to bind HLA-A2 in CTL. After thirty minutes, CTL cultured with test peptide, or control peptides, were tested for their response to antigen dose to the fluM58 peptide in a standard TNF bioassay. As shown in Figure 3, peptide P1S # 10 competes for the restricted presentation of HLA-A2 from fluM58, demonstrating that peptide P1S # 10 binds to HLA-A2. Mice were immunized by expressing the transgene for human HLA A2.1 as described by Theobald et al. (Proc. Na ti. Acad. Sci. USA 92: 11993-11997, 1995) with the following modifications. Mice were immunized with 62.5 μg of P1S # 10 and 120 μg of an I-Ab binding peptide derived from hepatitis B virus protein emulsified in incomplete Freund's adjuvant. Three weeks later, these mice were sacrificed in simple cell suspensions, prepared using a nylon mesh. The cells were then resuspended in 6 x 10 6 cells / ml in complete medium (as described above) and cultured in the presence of LPS blasts (transgenic A2 spleen cells cultured in the presence of 7 μg / ml dextran sulfate and 25 μg. / ml of LPS for 3 days), pulsed by P1S # 10 (2 μg / ml of P1S # 10 and 10 mg / ml of β2-microglobulin), irradiated (3000 rads). Six days later, the cells (5 x 10 5 / ml) were restimulated with 2.5 x 10 6 / ml of peptide-eluted EL4A2Kb cells, irradiated (20,000 rads), as described above, and 3 x lVrr.l of spleen feeder cells Transgenic A2 The cells were cultured in the presence of 20 U / ml of IL-2. The cells were restimulated on a weekly basis in the preparation for cloning. After three rounds of in vitro stimulation, a line was generated that recognized Jurkat A2Kg targets pulsed by P1S # 10 and Jurkat 5 targets transduced with P501S, as shown in Figure 4. A specific CTL line of P1S # 10 was cloned by limiting dilution analysis with EL4 A2KB tumor cells pulsed by peptide (1 x 104 cells / well) as stimulants and transgenic A2 spleen cells as feeders (5 x 105
cells / well) grown in the presence of 30U / ml of IL-2. On f the 14th, the cells were re-stimulated as before. On day 21, viable clones were isolated and kept in culture. As shown in Figure 5, five of these clones demonstrated specific cytolytic reactivity against AsKb Jurkat targets
transduced with P501S. These data indicate that P1S # 10 represents a naturally processed epitope of the P501S protein, which is expressed in the context of the human HLA-A2.1 molecule.
f EXAMPLE 7 CAPACITY OF HUMAN T CELLS TO RECOGNIZE PROSTATE TUMOR POLIPEPTIDES This example illustrates the ability of T cells specific for a prostate tumor polypeptide to recognize a human tumor.
Human CD8 + T cells were initiated in vitro to the peptide P2S-12 (SEQ ID NO 306) derived from P502S (also referred to as Jl-17), using dendritic cells according to the protocol of Van Tsai et al. (Cri tical Reviews in Immunology 18.65-75, 1998). The resulting CD8 + T cell microcultures were tested for their ability to recognize the P2S-12 peptide presented by autologous fibroblasts or fibroblasts that were transduced to express the P502S gene in an? -interferon ELISPOT assay (see Lalvani et al., J. Exp. Med. 186: 859-865, 1977). Briefly, lps T cell titration numbers were assayed in duplicate in 104 fibroblasts in the presence of 3 μg / ml of human β2-microglobulin and 1 μg / ml of P2S-12 peptide or control E75 peptide. In addition, T cells were tested simultaneously in autologous fibroblasts transduced with the P502S gene or as a control, fibroblasts transduced with HER-2 / neu. Before the assay, the fibroblasts were treated with 10 ng / ml of β-interferon for 48 hours to over-regulate MHC class I expression. One of the microcultures (# 5) showed strong recognition of both fibroblasts pulsed by peptide, as well as transduced fibroblasts in an? -interferon ELISPOT assay. Figure 2A shows that there was a strong increase in the number of? -interferon spots with increasing numbers of T cells in fibroblasts pulsed with the P2S-12 peptide (filled bars), but not with the control E75 peptide (empty bars) . This shows the ability of these T cells to specifically recognize the P2S-12 peptide. As shown in Figure 2B, this microculture also demonstrated an increase in the number of? -interferon blots with increasing numbers of T cells in transduced fibroblasts to express the P502S gene, but not the HER-2 / neu gene. These results provide additional confirmatory evidence that the P2S-12 peptide is a naturally processed epitope of the P502S protein. In addition, this also demonstrates that there exists in the repertoire of human T cells, high affinity of T cells that are able to recognize this epitope. These T cells should also be able to recognize human tumors, which express the P502S gene.
EXAMPLE 8 INITIATION OF CTL IN VIVO USING IMMUNIZATION OF NUDED DNA WITH A PROSTATE ANTIGEN The prostate tumor antigen Ll-12, as described above, is also referred to as P501S. HLA A2KB Tg mice were immunized (provided by Dr L. Sherman, The Scripps Research
Institute, La Jolla, CA) with 100 μg of VR10132-P501S, either intramuscularly or intradermally. The mice were immunized three times, with an interval of two weeks between immunizations. Two weeks after the last immunization, immune spleen cells were cultured with stimulator cells transduced with A2Kb-P501S Jurkat. The CTL lines were stimulated weekly. After two weeks of in vitro stimulation, CTL activity was assessed against targets transduced with P501S. Two out of 8 mice developed strong anti-P501S CTL responses. These results demonstrate that P501S contains at least one CTL epitope restricted by A "processed naturally.
EXAMPLE 9 GENERATION OF IN VITRO HUMAN CTL USING GENE INITIATION
COMPLETE AND STIMULATION TECHNIQUES
WITH PROSTATE TUMOR ANTIGEN Using full-gene initiation in vitro with autologous fibroblasts retrovirally traduced with P501S (see, eg, Yee et al, The Journal of Immunology, 157 (9): 4079-86, 1996), lines were derived Human CTLs that specifically recognize autologous fibroblasts transduced with P501S (also known as Ll-12), as determined by ELISPOT analysis of β-interferon, as described above. Using a panel of unequal HLA fibroblast lines transduced with P501S, it is shown that these CTL lines are class I alleles of restricted HLA-A2. Specifically, dendritic cells (DC) were differentiated from PBMC derived monocyte cultures from normal human donors by growing for five days in RPMI medium containing 50% human serum, 50 ng / ml human GM-CSF and 30 ng / ml of human IL-4. Following the culture, DC was infected overnight with recombinant P501S vaccinia virus in a multiplicity of infections (M.O. I) of five, and matured overnight by the addition of 3 μg / ml of CD40 ligand. The virus is inactivated by UV irradiation. CD8 + T cells were isolated using a magnetic bead system, and initiation cultures were started using standard culture techniques. The cultures were re-stimulated every 7-10 days using autologous primary fibroblasts transduced retrovirally with P501S. Following four stimulation cycles, the CD8 + T cell lines that specifically produced? -interferon were identified, when stimulated with autologous fibroblasts transduced with P501S. The specific activity of P501S could be sustained by continuous stimulation of cultures with fibroblasts transduced with P501S in the presence of IL-15. A panel of HLA-unequal fibroblast lines transduced with P501S was generated to define the response restriction allele. When measuring? -interferon in an ELISPOT assay, the specific response of P501S showed to be restricted by HLA-A2. These results demonstrate that a CTL response of CD8 + to P501S can occur.
EXAMPLE 10 IDENTIFICATION OF A PROCESSED NAIL EPITOPE OF NAUTRAL WAY CONTAINED WITHIN A PROSTATE TUMOR ANTIGEN The 9-mer peptide p5 (SEQ ID NO: 338) of the P703P antigen (also referred to as P20) was derived. The p5 peptide is immunogenic in human HLA-A2 donors and is a naturally processed epitope. The antigen-specific CD8 + T cells can be initiated following repeated m vitro stimulations with monocytes pulsed with the p5 peptide. These CTLs specifically recognize p5-pulsed target cells in both ELISPOT assays (as described above) and chromium release. Additionally, immunization of HLA-A2 transgenic mice with p5 leads to the generation of CTL lines that recognize a variety of target cells transduced with P703P, expressing either HLA-A2Kb or HLA-A2. Specifically, HLA-A2 transgenic mice were immunized subcutaneously in the foot pad with 100 μg of p5 peptide, together with 140 μg of hepatitis B virus core peptide (a Th peptide) in incomplete helper of Freund. Three weeks after the immunization, the spleen cells of immunized mice were stimulated in vitro with LPS blasts pulsed with peptide. CTL activity was assessed by chromium release assay five days after primary m vitro stimulation. The retrovirally transduced cells, expressing the control antigen P703P and HLA-A2Kb, were used as targets. CTL lines that specifically recognized both targets pulsed by p5 were identified, as well as targets expressing P703P Human vit'O initiation experiments demonstrated that o5 peptide is mmunogenic in humans Dendritic cells (DC) were differentiated from monocyte cultures derived from PBMC from normal human donors when cultured for five days in RPMI medium containing 10% human serum, 50 ng / ml of human GM-CSF and 30 ng / ml of human IL-4. Following the culture, DC were pulsed with p5 peptide and cultured with GM-CSF and IL-4 together with PBMC enriched with CD8 + T cells. The CTL lines were re-stimulated on a weekly basis with monocytes pulsed with p5. Five to six weeks after the initiation of CTL cultures, CTL recognition of target cells pulsed by p5 was demonstrated.
EXAMPLE 11 EXPRESSION OF AN ANTIGEN DERIVED FROM CHEST TUMOR IN PROSTATE Isolation of the B305D antigen from breast tumor by differential display is described in US Patent Application no. 08 / 700,014, filed on August 20, 1996. Several different splice forms of this antigen were isolated. The cDNA sequences determined for these splice forms are provided in SEQ ID NO: 366-375, with the predicted amino acid sequences corresponding to the sequences of SEQ ID NO: 292, 298 and 301-303 being provided in SEQ ID NO: 299-306, respectively. The expression levels of B305D in a variety of tumor and normal tissues were examined by real-time PCR and by Northern analysis. The results indicated that B305D is highly expressed in breast tumor, prostate tumor, normal prostate and normal testes, being low to undetectable expression in all other tissues examined (colon tumor, lung tumor, ovarian tumor, and bone marrow, colon, kidney, liver, lung, ovary, skin, small intestine, normal stomach).
EXAMPLE 12 PROVOCATION OF ANTIGEN-SPECIFIC ANTIGEN CTL RESPONSES FROM PROSTATE TUMOR IN HUMAN BLOOD This example illustrates the ability of a prostate tumor antigen to elicit a CTL response in the blood of normal humans. Autologous dendritic cells (DC) were differentiated from monocyte cultures derived from PBMC from normal donors by growth for five days in RPMI medium containing
% human serum, 50 ng / ml of GMCSF and 30 ng / ml of IL-4.
Following the culture, DC was infected overnight with vaccinia virus expressing recombinant P501S at M.O. I. of 5 and matured for 8 hours by the addition of 2 micrograms / ml of CD40 ligand. The virus was inactivated by UV irradiation, the CD8 + cells were isolated by positive selection using magnetic beads, and the initiation cultures were started in 24-well plates. Following five cycles of stimulation, CD8 + lines that specifically produced interferon-gamma were identified when stimulated with fibroblasts transduced with autologous P501S. The P501S-specific activity of the 3A-1 cell line could be maintained by following additional stimulation cycles in autologous B-LCL transduced with P501S. Line 3A-1 was shown to specifically recognize autologous B-LCL transduced to express P501S, but not EGFP-transduced autologous B-LCL, as measured by cytotoxicity assays (51 Cr release) and mferferon-gamma production (intersphere-gamma Elispot see above and Lalvam et al., J. Exp. Med. 186: 859-865, 1997). The results of these tests are presented in Figures 6A and 6B.
EXAMPLE 13 IDENTIFICATION OF PROSTATE TUMOR ANTIGENS THROUGH MICRO-REGULAR ANALYSIS This example describes the isolation of certain prostate tumor polypeptide from a prostate tumor cDNA library. A human prostate tumor cDNA expression library was classified, as described using microarray analysis, to identify clones exhibiting at least one three-fold over-expression in prostate tumor and / or normal prostate tissue, as compare with normal non-prostate tissues (not including testes). 372 clones were identified, and 319 were successfully sequenced.1 Table I presents a summary of these clones, which are shown in SEQ ID NOS: 385-400 Of these sequences, SEQ ID NOS: 386, 389, 390 and 392 correspond to novel genes, and SEQ ID NOS 393 and 396 correspond to sequences previously identified.The rest (SEQ ID NOS: 385, 387, 388, 391, 394, 395 and 397-400) correspond to known sequences, as shown in Table I.
Table I Summary of Prostate Tumor Antigens Known Genes Pre-Generated Genes Newly Identified Gamma Cell Strand P504S 23379 (SEQ ID NO: 389)
T Calicrein P1000C 23399 (SEQ ID NO: 392)
Vector P501S 23320 (SEQ ID NO: 386)
Protein mRNA CGI-82 P503S 23381 (SEQ ID NO: 390)
(23319, SEQ ID NO: 385) PSA P510S Aid. 6. Dehid. P784P L-? D? Tol-2 P502S dehydrogenase (23376; SEQ ID NO: 388) PDEF of P706P transcription factor Ets (22672; SEQ ID NO: 398) hTGR (22678; SEQ ID 19142.2, bangur.seq NO: 399 ) (22621; SEQ ID NO: 396) KIAA0295 (22685; SEQ ID 55.66.1 Wang (23404; NO • i 20 ^ SEQ ID NO: 393) Prostatic P7I2P acid phosphatase (22655; SEQ ID NO: 397) Tra sg ] tet? nase? 778P 22. _, SQ ID O 255 Table I (continued)
CGI-82 showed an overexpression of 4.06 times in prostate tissues compared to other normal tissues tested. It was over-expressed in 43% of prostate tumors, 25% of normal prostate, and was not detected in other normal tissues tested. L-iditiol-2 dehydrogenase showed an over-expression of 4.94 times in prostate tissues compared to other normal tissues tested. It was over-expressed in 90% of prostate tumors, 100% normal prostate and was not detected in other normal tissues tested. PDEF transcription factor Ets showed an overexpression of 5.55 fold in prostate tissues compared to other normal tissues tested. It was over-expressed in 47% of prostate tumors, 25% of normal prostate and was not detected in other normal tissues tested. hTGRl showed 9-11 fold over-expression in prostate tissues compared to other normal tissues tested. It was over-expressed in 63% of prostate tumors and was not detected in normal tissues tested including normal prostate. KIAA0295 showed 5.59 fold over-expression in prostate tissues compared to other normal tissues tested. It was over-expressed in 47% of prostate tumors, had low to no detectable expression in normal tissues tested including normal prostate tissues. Prostatic acid phosphatase showed an overexpression of 9.14 times in prostate tissues compared to other normal tissues tested. It was overexpressed in 67% of prostate tumors, 50% of normal prostate and was not detected in other normal tissues tested. Transglutaminase showed overexpression of 14.84 times in prostate tissues compared to other normal tissues tested. It was over-expressed in 30% of prostate tumors, 50% of normal prostate and is not detected in other normal tissues tested. The high density lipoprotein binding protein (HDLBP) showed 28.06 fold over-expression in prostate tissues compared to other normal tissues tested. It was over-expressed in 97% of prostate tumors, 75% of normal prostate and is not detectable in all other normal tissues tested. CGI-69 showed 3.56 fold over-expression in prostate tissues compared to other normal tissues tested. It is a low abundance gene, detected in more than 90% of prostate tumors and in 75% of normal prostate tissues. The expression of this gene in normal tissues was very low. KIAA0122 showed overexpression of 4.24 fold in prostate tissues compared to other normal tissues tested. It was over-expressed in 57% of prostate tumors, it was not detectable in all normal tissues tested including normal prostate tissues. 19142.2 bangur showed 23.25-fold over-expression in prostate tissues compared to other normal tissues tested. It was over-expressed in 97% of prostate tumors and 100% of normal prostate. It was not detectable in other normal tissues tested. 5566.1 Wang showed overexpression of 3.31 times in prostate tissues compared to other normal tissues tested. It was over-expressed in 975 of prostate tumors, 75% of normal prostate and was also over-expressed in bone marrow, normal pancreas and activated PBMC. The new clone 23379 showed overexpression of 4.86 fold in prostate tissues compared to other normal tissues tested. It was detectable in 97% of prostate tumors and 75% of normal prostate and is not detectable in all other normal tissues tested. The new clone 23399 showed overexpression of 4.09 times in prostate tissues compared to other normal tissues tested. It was over-expressed in 27% of prostate tumors and was not detectable in all normal tissues tested including normal prostate tissues. The new clone 23320 showed overexpression of 3.15 times in prostate tissue compared to other normal tissues tested. It was detectable in all prostate tumors and 50% of normal prostate tissues. It was also expressed in normal colon and trachea. Other normal tissues do not express this gene at a high level.
EXAMPLE 14 IDENTIFICATION OF PROSTATE TUMOR ANTIGENS USING ELECTRONIC SUBSTRACTION This example describes the use of an electronic subtraction technique to identify prostate tumor antigens. Specific prostate-specific genes present in the GenBank human EST database were identified by electronic subtraction (similar to that described by Vasmatizis et al., Proc.Nat.Acid.Sci.USA 95: 300-304, 1998). The sequences of EST clones (43,482) derived from several prostate libraries were obtained from the public human EST database GenBAnk. Each prostate EST sequence was used as a question sequence in a BLASTN search (National Center for Biotechnology Information) against the human EST database. All matches considered identical (equal sequence length> 100 base pairs, density of identical matches over this region> 70%) were grouped (aligned) together in a bandlet. The bouquets containing more than 200 ESTs were discarded, because they probably represented repetitive elements or highly expressed genes, such as those for ribosomal proteins. If two or more bouquets shared common ESTs, those bouquets were grouped in a "super-bouquet", resulting in 4,345 super-corsages of prostate. The records for the 479 human cDNA libraries represented in the GenBank release were downloaded to create a database of these cDNA library records. These 479 cDNA libraries were grouped into three groups, Plus (normal prostate and prostate tumor libraries, and breast cell lines, in which expression was desired), Minus (libraries of other normal adult tissues, in which expression was not desirable), and Other (fetal tissue, infantile tissue, tissues found only in women, non-prostate tumors and cell lines other than prostate cell lines, in which expression was considered irrelevant). A summary of these groups of libraries is presented in Table II.
Table II Prostate cDNA libraries and ESTs
Each super-corsage was analyzed in terms of the ESTs within the super-corsage. The tissue source of each EST clone was noted and used to classify the super-bouquets into four groups: EST clones type 1 found in the Plus group libraries only; no expression detected in the Minus or Other group libraries; EST type 2 clones found in the Plus and Other group libraries only; no expression detected in the Minus group; EST clones type 3 found in the Plus, Minus and Other group libraries, but the expression in the Plus group is greater than in any of the Minus or Other groups; and EST type 4 clones found in the Plus, Minus and Other group libraries, but the expression in the Plus group is greater than the expression in the Minus group. This analysis identified 4,445 chest corsages (see Table III). Of these clusters, 3,172 EST clones were ordered from Research Genetics Inc., and were received as frozen glycerol stocks in 96-well plates.
Table III Summary of Prostate Caplets
The inserts were amplified by PCR using amino-linked PCR primers for Synteni microarray analysis. When more than one PCR product was obtained for a particular clone, that PCR product was not used for expression analysis. In total, 2,528 clones of the electronic subtraction method were analyzed by microarray analysis to identify electronic subtraction breast clones that had tumor mRNA vs. normal high tissue. Such classifications were made using a Synteni microarray (Palo Alto, CA), according to the manufacturer's instructions (and essentially as described by Schena et al., Proc. Na ti. Acad. Sci. USA 93: 10614-10619, 1996 and Heller et al., Proc. Na ti, Acad. Sci. USA 94: 2150-2155, 1997). Within these analyzes, the clones were fixed in the leaflet, which was then tested with fluorescent probes generated from normal prostate and tumor cDNA, as well as various other normal tissues. The slides were scanned and the fluorescence intensity was measured. Clones with an expression ratio greater than 3 (ie, the level in prostate tumor cDNA was at least three times the level in normal prostate cDNA) were identified as prostate tumor specific sequences (Table IV). The sequences of these clones are provided in SEQ ID NOS: 401-453, with certain novel sequences shown in SEQ ID NOS: 407, 413, 416-419, 422, 426, 427 and 450.
Table IV Specific clones of prostate tumor F
F F
F
EXAMPLE 15 ADDITIONAL IDENTIFICATION OF PROSTATE TUMOR ANTIGENS
USING MICRO-REGULAR ANALYSIS This example describes the isolation of additional prostate tumor polypeptides from a prostate tumor cDNA library.
A human prostate tumor cDNA expression library as described above, was classified using microarray analysis to identify clones exhibiting at least one f over-expression three times in prostate tumor tissue and / or normal prostate, as compared to normal non-prostate tissues (not including testes). 142 clones were identified and sequenced. Certain of these clones are shown in SEQ ID NOS: 454-467. Of these sequences SEQ ID NOS: 459-461 correspond to novel genes. The others (SEQ ID NOS 454-458 and 461-467) 10 correspond to known sequences. f EXAMPLE 16 ADDITIONAL CHARACTERIZATION OF PROSTATE TUMOR ANTIGEN P710P This example describes the full-length cloning of 15 P710P. The prostate cDNA library described above was classified with the P710P fragment described above. One million colonies were plated on LB / ampicillin plates. Nylon membrane filters were used to lift these colonies, and the cDNAs collected by these filters were then denatured and cross-linked to the filters by UV light. The P710P fragment was radiolabelled and used to hybridize with the filters. Positive cDNA clones were selected and their cDNAs recovered and sequenced by an automatic ABI sequencer. Four sequences were obtained and are presented in SEQ ID NOS: 468-471.
From the foregoing, it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without departing from the spirit and scope of the invention. Accordingly, the present invention is not limited except by the appended claims.
F
LIST OF SEQUENCES < 110 > Corixa Corporation < 120 > COMPOUNDS FOR IMMUNOTHERAPY AND DIAGNOSIS OF PROSTATE CANCER AND METHODS FOR USE < 130 > 210121.42701PC < 140 > PCT < 141 > 1999-07 -08 < 160 > 472 < 170 > FastSEQ for Windows Version 3.0 < 210 > 1 < 211 > 814 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (814) < 223 > n = A, T, C or G < 400 > 1 tttttttttt tttttcacag tataacagct ctttatttct gtgagttcta ctaggaaatc 60 atcaaatctg agggttgtct ggaggacttc aatacacctc cccccatagt gaatcagctt 120 ccagggggtc cagtccctct ccttacttca tccccatccc atgccaaagg aagaccctcc 180 ctccttggct cacagccttc tctaggcttc ccagtgcctc caggacagag tgggttatgt 240 tttcagctcc atccttgctg tgagtgtctg gtgcgttgtg cctccagctt ctgctcagtg 300 cttcatggac agtgtccagc acatgtcact ctccactctc tcagtgtgga tccactagtt 360 ctagagcggc cgccaccgcg gtggagctcc agcttttgtt ccctttagtg agggttaatt 420 gcgcgcttgg cgtaatcatg gtcataactg tttcctgtgt tccgctcaca gaaattgtta 480 attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc ctaatgagtg 540 anctaactca cattaattgc gttgcgctca ctgnccgctt tccagtcngg aaaactgtcg 600 tgccagctgc attaatgaat cggccaacgc ncggggaaaa gcggtttgcg ttttgggggc 660 tcttccgctt ctcgctcact nantcctgcg ctcggtcntt cggctgcggg gaacggtatc 720 ggnggtatta actcctcaaa cggttatccn naaatcnggg gatacccngg aaaaaanttt 780 aacaaaaggg cancaaaggg cngaaacgta aaaa 814
< 210 > 2 < 211 > 816 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (816) < 223 > n = A, T, C or G < 400 > 2 acagaaatgt tggatggtgg agcacccttc tatacgactt acaggacagc agatggggaa 60 ttcatggctg ttggagcaat agaaccccag ttctacgagc tgctgatcaa aggacttgga 120 aagtttgcag atgtatttgc aaagaagacg aaggcagagt ggtgtcaaat ctttgacggc 240 gatgcct gtgtgactcc ggttctgact tttgaggagg ttgttcatca tgatcacaac 300 aaggaacggg gctcgtttat caccagtgag gagcaggacg tgagcccccg ccctgcacct 360 ctgctgttaa acaccccagc catcccttct ttcaaaaggg atccactagt tctagaagcg 420 gccgccaccg cggtggagct ccagcttttg ttccctttag tgagggttaa ttgcgcgctt 480 ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt tatccgctca caattccccc 540 aacatacgag ccggaacata aagtgttaag cctggggtgc ctaatgantg agctaactcn 600 cattaattgc gttgcgctca ctgcccgctt tccagtcggg aaaactgtcg tgccactgcn 660
F ttantgaatc ngccaccccc cgggaaaagg cggttgcntt ttgggcctct tccgctttcc 720 tcgctcattg atcctngcnc ccggtcttcg gctgcggnga acggttcact cctcaaaggc 780 ggtntnccgg ttatccccaa acnggggata cccnga 816 < 210 > 3 < 211 > 773 15 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > 20 different feature < 222 > (1) ... (773) < 223 > n = A, T, C or G
F < 400 > 3 cttttgaaag aagggatggc tggggtgttt aacagcagag gtgcagggcg ggggctcacg 60
tcctgctcct cactggtgat aaacgagccc cgttccttgt tgtgatcatg atgaacaacc 120 tcctcaaaag tcagaaccgg ágtcacacag gcatctgtgc cgtcaaagat ttgacaccac 180 tctgccttcg tcttctttgc aaatacatct gcaaacttct tcttcatttc tggccaatca 240 tccatgctca tctgattggg aagttcatca gactttagtc canntccttt gatcagcagc 300 cgtagaact ggggttctat tgctccaaca gccatgaatt ccccatctgc tgtcctgtaa 360
gtcgtataga aaggtgctcc accatccaac atgttctgtc ctcgaggggg ggcccggtac 420 ccaattcgcc ctatantgag tcgtattacg cgcgctcact ggccgtcgtt ttacaacgtc 480 gtgactggga aaaccctggg cgttaccaac ttaatcgcct tgcagcacat ccccctttcg 540 ccagctgggc gtaatancga aaaggcccgc accgatcgcc cttccaacag ttgcgcacct 600 gaatgggnaa atgggacccc cctgttaccg cgcattnaac ccccgcnggg tttngttgtt 660
acccccacnt nnaccgctta cactttgcca gcgccttanc gcccgctccc tttcnccttt 720 cttcccttcc tttcncnccn ctttcccccg gggtttcccc cntcaaaccc cna 773 < 210 > 4 < 211 > 828 40 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > 45 different feature < 222 > (1) ... (828) < 223 > n = A, T, C or G < 400 > 4 cctcctgagt cctactgacc tgtgctttct ggtgtggagt ccagggctgc taggaaaagg 60
50 cacaggtgta aatgggcaga tgccaatgtt tctgaaatgg gtataatttc gtcctctcct 120 tcggaacact ggctgtctct gaagacttct cgctcagttt cagtgaggac acacacaaag 180 acgtgggtga ccatgttgtt tgtggggtgc agagatggga ggggtggggc ccaccctgga 240 agagtggaca gtgacacaag gtggacactc tctacagatc actgaggata agctggagcc 300 acaatgcatg aggcacacac acagcaagga tgacnctgta aacatagccc acgctgtcct 360
55 ..: -, j; ac g gaagcctan atnaggccgt gagcanaaag aaggggagga tccactagtt 420 ctar.ascggc cgccaccgcg gtgganctcc ancttttgtt ccctttagtg agggttaatt 480"-'-; tc * - r gg cttaatcatg gtcatanctn tttcctgtgt gaaattgtta tccgctcaca 540
= .- " '- ?. ~ ac3?.?.;; Acganc cggaaacata aantgtaaac ctggggtgcc taatgantga 600 tcaca CTAA ttaattgcgt tgcgctcact gcccgctttc caatcnggaa acctg CTTG 660 ccncttgcat tnatgaatcn gccaaccccc ggggaaaagc gtttgcgttt tgggcgctct 720 tccgcttcct cnctcantta ntccctncnc tcggtcattc cggctgcngc aaaccggttc 780 accncctcca aagggggtat tccggtttcc ccnaatccgg gganancc 828 < 210 > 5 < 211 > 834 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > miscellaneous feature < 222 > (1) ... ( 834) < 223 > n = A, T, C or G < 400 > 5 tttttttttt tttttactga tagatggaat ttattaagct tttcacatgt gatagcacat 60 agttttaatt gcatccaaag tactaacaaa aactctagca atcaagaatg gcagcatgtt 120 attttataac aatcaacacc tgtggctttt aaaatttggt tttcataaga taatttatac 180 tgaagtaaat ctagccatgc ttttaaaaaa tgctttaggt cactccaagc ttggcagtta 240 acatttggca taaacaataa taaaacaatc acaatttaat aaataacaaa tacaacattg 300 taggccataa tcatatacag tataaggaaa aggtggtagt gttgagtaag cagttattag 360 aatagaatac cttgg cctct atgcaaatat gtctagacac tttgattcac tcagccctga 420 cattcagttt tcaaagtagg agacaggttc tacagtatca ttttacagtt tccaacacat 480 tgaaaacaag tagaaaatga tgagttgatt tttattaatg cattacatcc tcaagagtta 540 tcaccaaccc ctcagttata aaaaattttc aagttatatt agtcatataa cttggtgtgc 600 ttagtgctaa ttattttaaa atggattaag tgaagacaac aatggtcccc taatgtgatt 660 atttttacca gatattggtc gcttctaaat ctnaactttc aggcttttga actggaacat 720 tgnatnacag tgttccanag ttncaaccta ctggaacatt acagtgtgct tcattcaaaa 780 tgttattttg ttaaaaatta aattttaacc tggtggaaaa ataatttgaa atna 834
< 210 > 6 < 211 > 818 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (818) < 223 > n = A, T, C or G < 400 > 6 tttttttttt tttttttttt aagaccctca tcaatagatg gagacataca gaaatagtca 60 aaccacatct acaaaatgcc agtatcaggc ggcggcttcg aagccaaagt gatgtttgga 120 tgtaaagtga aatattagtt ggcggatgaa gcagatagtg aggaaagttg to ccaataat 180 gacgtgaagt ccgtggaagc ctgtggctac aaaaaatgtt tgccgtcgga gagccgtaga 240 ggagactcga aatggtgaag agtactctga ggcttgtagg agggtaaaat agagacccag 300 taaaattgta ataagcagtg cttgaattat ttggtttcgg ttgttttcta ttagactatg 360 gtgagctcag gtgattgata ctcctgatgc gagtaatacg gatgtgttta ggagtgggac 420 ttctagggga tttagcgggg tgatgcctgt tgggggccag tgccctccta gttggggggt 480 aggggctagg ctggagtggt aaaaggctca gcgaagaaaa gaaaaatcct aaacttctga 540 ggtaataaat aggattatcc cgtatcgaag gcctttttgg acaggtggtg tgtggtggcc 600 ttggtatgtg ctttctcgtg ttacatcgcg ccatcattgg tatatggtta gtgtgttggg 660 ttantanggc ctantatgaa gaacttttgg antggaatta aatcaatngc ttggccggaa 720 nggctnaaaa gtcattanga ggccctgtta ngggtctggg ctnggtttta cccnacccat 780 ccccggacna ggaatncncc attcttaa ntgnatccct 818
< 210 > 7 < 211 > 817 < 212 > DNA < 213 > Homo sapien < 220 > 5 < 221 > diverse feature < 222 > (1) ... (817) < 223 > n = A, T, C or G < 400 > Tttttttttt tttttttttt July 10 tggctctaga gggggtagag ggggtgctat agggtaaata 60 cgggccctat ttcaaagatt tttaggggaa ttaattctag gacgatgggt atgaaactgt 120 ggtttgctcc acagatttca gagcattgac cgtagtatac ccccggtcgt gtagcggtga 180 aagtggtttg gtttagacgt ccgggaattg catctgtttt taagcctaat gtggggacag 240 ctcatgagtg caagacgtct tgtgatgtaa ttattatacn aatgggggct tcaatcggga 300
gtactactcg attgtcaacg tcaaggagtc gcaggtcgcc tggttctagg aataatgggg 360 gaagtatgta ggaattgaag attaatccgc cgtagtcggt gttctcctag gttcaatacc 420 attggtggcc aattgatttg atggtaaggg gagggatcgt tgaactcgtc tgttatgtaa 480 aggatncctt ngggatggga ggactangga aggcnatnaa tnaatggcgg gcangatatt 540 tcaaacngtc tctanttcct gaaacgtctg aaatgttaat aanaartaan tttngttatt 600
gaatnttnng gaaaagggct tacaggacta gaaaccaaat angaaaanta atnntaangg 660 cnttatcntn aaaggtnata accnctccta tnatcccacc caatngnatt ccccacncnn 720 acnattggat nccccanttc canaaanggc cnccccccgg tgnannccnc cttttgttcc 780 cttnantgan ggttattcnc ccctngcntt atcancc 817 f 25 < 210 > 8 < 211 > 799 < 212 > DNA < 213 > Homo sapien 30 < 220 > < 221 > diverse feature < 222 > (1) ... (799) < 223 > n = A, T, C or G 35 < 400 > 8 catttccggg tttactttct aaggaaagcc gagcggaagc tgctaacgtg ggaatcggtg 60 cataaggaga actttctgct ggcacgcgct agggacaagc gggagagcga ctccgagcgt 120 cgtcccagaa ctgaagcgca ggtggacttg gcactgaaac agctgggaca catccgcgag 180 tacgaacagc gcctgaaagt gctggagcgg gaggtccagc agtgtagccg cgtcctgggg 240
40 tgggtggccg angcctganc cgctctgcct tgctgccccc angtgggccg ccaccccctg 300 acctgcctgg gtccaaacac tgagccctgc tggcggactt caagganaac ccccacangg 360 f ggattttgct cctanantaa ggctcatctg ggcctcggcc cccccacctg gttggccttg 420 tctttgangt gagccccatg tccatctggg ccactgtcng gaccaccttt ngggagtgtt 480 ctccttacaa ccacannatg cccggctcct cccggaaacc antcccancc tgngaaggat 540
45 caagncctgn atccactnnt nctanaaccg gccnccnccg cngtggaacc cnccttntgt 600 tccttttcnt tnagggttaa tnncgccttg gccttnccan ngtcctncnc nttttccnnt 660 gttnaaattg ttangcnccc nccnntcccn cnncnncnan cccgacccnn annttnnann 720 ncctgggggt nccnncngat tgacccnncc nccctntant tgcnttnggg nncnntgccc 780 799 ctttccctct ngggar.ncg
50 < 210 > 9 < 211 > 801 < 212 > DNA < 213 > Homo sapien 53 < 220 > < 221 > diverse feature < 222 > (I X ... (801) < 223 > n = A, T, C, or G < 400 > 9 acgccttgat cctcccaggc tgggactggt tctgggagga gccgggcatg ctgtggtttg 60
taangatgac actcccaaag gtggtcctga cagtggccca gatggacatg gggctcacct 120 caaggacaag gccaccaggt gcgggggccg aagcccacat gatccttact ctatgagcaa 180 aatcccctgt gggggcttct ccttgaagtc cgccancagg gctcagtctt tggacccang 240 caggtcatgg ggttgtngnc caactggggg aaanggcnca ccncaacgca gggcctcngn 300 cacccatccc angacgcggc tacactnctg gacctcccnc tccaccactt tcatgcgctg 360
ttcntacccg cgnatntgtc ccanctgttt cngtgccnac tccancttct nggacgtgcg 420 ctacatacgc ccggantcnc nctcccgctt tgtccctatc cacgtnccan caacaaattt 480 cnccntantg caccnattcc cacntttnnc agntttccnc nncgngcttc cttntaaaag 540 ggttganccc cggaaaatnc cccaaagggg gggggccngg tacccaactn ccccctnata 600 gctgaantcc ccatnaccnn gnctcnatgg anccntccnt tttaannacn ttctnaactt 660
gggaanancc ctcgnccntn cccccnttaa tcccnccttg cnangnncnt cccccnntcc 720 ncccnnntng gcntntnann cnaaaaaggc ccnnnancaa tctcctnncn cctcanttcg 780 ccanccctcg aaatcggccn c 801 < 210 > 10 20 < 211 > 789 < 212 > DNA < 213 > Homo sapien
diverse feature < 222 > (1) ... (789) < 223 > n = A, T, C or G < 400 > 10 30 cagtctatnt ggccagtgtg gcagctttcc ctgtggctgc cggtgccaca tgcctgtccc 60 acagtgtggc cgtggtgaca gcttcagccg ccctcaccgg gttcaccttc tcagccctgc 120 agatcctgcc ctacacactg gcctccctct accaccggga gaagcaggtg ttcctgccca 180 aataccgagg ggacactgga ggtgctagca gtgaggacag cctgatgacc agcttcctgc 240 caggccctaa gcctggagct cccttcccta atggacacgt gggtgctgga ggcagtggcc 300
tgctcccacc tccacccgcg ctctgcgggg cctctgcctg tgatgtctcc gtacgtgtgg 360 tggtgggtga gcccaccgan gccagggtgg ttccgggccg gggcatctgc ctggacctcg 420 tagtgcttcc ccatcctgga tgctgtccca ngtggcccca tccctgttta tgggctccat 480 tgtccagctc agccagtctg tcactgccta tatggtgtct gccgcaggcc tgggtctggt 540 ttgctacaca cccatttact ggtantattt gacaagaacg anttggccaa atactcagcg 600
40 ttaaaaaatt ccagcaacat tgggggtgga aggcctgcct cactgggtcc aactccccgc 660 tcctgttaac cccatggggc tgccggcttg gccgccaatt tctgttgctg ccaaantnat 720 gtggctctct gctgccacct gttgctggct gaagtgcnta cngcncanct nggggggtng 780
F ggngttccc 789
45 < 210 > 11 < 211 > 772 < 212 > DNA < 213 > Homo sapien 50 < 220 > < 221 > diverse feature < 222 > (1) ... (772) < 223 > n = A, T, C or G 55 < 400 > 11 ccaaatatta cccaccctac gacaccaaca cagaaaagct agcaatggat tcccttctac 60 tttgttaaat aaataagtta aatatttaaa tgcctgtgtc tctgtgatgg caacagaagg 120 accaacaggc cacatcctga taaaaggtaa gaggggggtg gatcagcaaa aagacagtgc 180 tgtgggctga ggggacctgg ttcttgtgtg ttgcccctca ggactcttcc cctacaaata 240 actttcatat gttcaaatcc catggaggag tgtttcatcc tagaaactcc catgcaagag 300 cgaagctgca ctacattaaa ggttaagggg cttanagatg ggaaaccagg tgactgagtt 360 tattcagctc ccaaaaaccc ttctctaggt gtgtctcaac taggaggcta gctgttaacc 420 ctgagcctgg gtaatccacc tgcagagtcc ccgcattcca gtgcatggaa cccttctggc 480 ctccctgtat aagtccagac tgaaaccccc ttggaaggnc tccagtcagg cagccctana 540 aactggggaa aaaagaaaag gacgccccan cccccagctg tgcanctacg cacctcaaca 600 gcagcaaaaa gcacagggtg aaccacttta ctttggcaca ngggggggca aacaaaaact 660 accccggcac cccnangggg gttaacagga ancngggnaa aattnaggca cntggaaccc 720 ggcccnccac cccnaatntt gctgggaaat ctaaattntt you ttttcctccc 772
< 210 > 12 < 211 > 751 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (751) < 223 > n = A, T, C or G < 40 0 > 12 gccccaattc cagctgccac accacccacg gtgactgcat tagttcggat gtcatacaaa 60 agctgattga agcaaccctc tactttttgg tcgtgagcct tttgcttggt gcaggtttca 120 ttggctgtgt tggtgacgtt gtcattgcaa cagaatgggg gaaaggcact gttctctttg 180 aagtanggtg agtcctcaaa atccgtatag ttggtgaagc cacagcactt gagccctttc 240 atggtggtgt tccacacttg agtgaagtct tcctgggaac cataatettt cttgatggca 300 ggcactacca gcaacgtcag ggaagtgctc agccattgtg gtgtacacca to gcgaccac 360 agcagctgcn acctcagcaa tgaagatgan gaggangatg aagaagaacg tcncgagggc 420 acacttgctc teagtettan caccatanca accaananca gcccntgaaa aagaccacna 480 gatgaagaaa cnccggctgc tnaccccncg ttgacaaact tgcatggcac tggganccac 540 aaaatcttca agtggcccna aaaaggatgc cccatcnatt gaccccccaa atgcccactg 600 ccaacagggg ctgccccacn cnennaaega tganecnatt gnacaagatc tncntggtct 660 tnatnaacnt gaaccctgcn tngtggctcc tgttcaggnc cnnggcctga cttctnaann 720 gaagncccca aangaacten cngganannc 751 g
< 210 > 13 < 211 > 729 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (729) < 223 > n = A, T, C or G < 400 > 13 gasccaggcg tccctctgcc tgcccactca gtggcaacac ccgggagctg ttttgtcctt 60 tgtggancct cagcagtncc etettteaga actcantgcc aaganccctg aacaggagcc 120 accatgeagt gcttcagctt cattaagacc atgatgatcc tcttcaattt gctcatcttt 180 ctgtgtggtg cagccctgtt ggcagtgggc atctgggtgt caategatgg gg atccttt 240 ctgaagátct tcgggccact gtcgtccagt gccatgcagt ttgtcaacgt gcgctacttc 300 ctcatcgcag ccggcgttgt ggtcttagct ctaggtttcc tgggctgcta tggtgctaag 360 actgagagca agtgtgccct cgtgacgttc ttcttcatcc tcctcctcat cttcattgct 420 zp. -t-tgcaa tgctgtggtc gccttggtgt acaccacaat ggctgagcac ttcctgacgt 480 t ctggtaat gcctgccatc aanaaaagat tatgggttcc caggaanact t tactcaagt 540 g ttggaacac caccatgaaa gggctcaagt gctgtggctt cnnccaacta tacggatttt 600 aaaaantcac ctacttcaaa gaaaanagtg cctttccccc atttttgttg caattgacaa 660 acgtccccaa cacagccaat tgaaaacctg cacccaaccc aaangggtcc ccaaccanaa attnaaggg 720 729
< 210 > 14 < 211 > 816 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (816) < 223 > n = A, T, C or G < 400 > 14 tgctcttcct caaagttgtt cttgttgcca taacaaccac cataggtaaa gcgggcgcag 60 tgttcgctga aggggttgta gtaccagcgc gggatgctct ccttgcagag tcctgtgtct 120 ggcaggtcca cgcagtgccc tttgtcactg gggaaatgga tgcgctggag ctcgtcaaag 180 ccactcgtgt atttttcaca ggcagcctcg tccgacgcgt cggggcagtt gggggtgtct 240 tcacactcca ggaaactgtc natgcagcag ccattgctgc agcggaactg ggtgggctga 300 cangtgccag agcacactgg atggcgcctt tccatgnnan gggccctgng ggaaagtccc 360 tganccccan anctgcctct caaangcccc accttgcaca ccccgacagg ctagaatgga 420 atcttcttcc cgaaaggtag ttnttcttgt tgcccaancc anccccntaa acaaactctt 480 gcanatctgc tccgnggggg tcntantacc ancgtgggaa aagaacccca ggcngcgaac 540 tggatncgaa caancttgtt gcnataatct nctnttctgc gcaccantna ttggtggaca 600 ctgtnnanct ttagnccntg gtcctcntgg gttgnncttg aacctaatcn ccnntcaact 660 gggacaaggt aantngccnt cctttnaatt cccnancntn ccccctggtt tggggttttn 720 cncnctccta ccccagaaan nccgtgttcc cccccaacta ggggccnaaa ccnnttnttc 780 cacaaccctn ccccacccac gggttcngnt ggttng 816
< 210 > 15 < 211 > 783 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (783) < 223 > n = A, T, C or G < 400 > 15 ccaaggcctg ggcaggcata nacttgaagg tacaacccca ggaacccctg gtgctgaagg 60 atgtggaaaa cacagattgg cgcctactgc ggggtgacac ggatgtcagg gtagagagga 120 aagacccaaa ccaggtggaa ctgtggggac tcaaggaang cacctacctg ttccagctga. 180 cagtgactag ctcagaccac ccagaggaca cggccaacgt cacagtcact gtgctgtcca 240 ccaagcagac agaagactac tgcctcgcat ccaacaangt gggtcgctgc cggggctctt 300 tcccacgctg gtactatgac cccacggagc agatctgcaa gagtttcgtt tatggaggct 360 gcttgggcaa caagaacaac taccttcggg aagaagagtg cattctancc tgtcngggtg 420 tgcaaggtgg gcctttgana ngcanctctg gggctcangc gactttcccc cagggcccct 480 ccatggaaag gcgccatcca ntgttctctg gcacctgtca ttccgctgca gcccacccag 540 ncaatggctg ctgcatcnac antttcctng aattgtgaca ntgcccccaa acacccccca 600 ccctcccaac aaagcttccc tgttsiaaaaa tacnccantt ggcttttnac aaacncccgg 660 cncctccntt ttccccnntn aacaaagggc nctngcnttt gaactgcccn aacccnggaa 720 tctnccnngg aaaaantncc ccccctggtt cctnnaancc cctccncnaa anctnccccc 780 ccc 783 < 210 > 16 < 211 > 801 < 212 > DNA < 213 > Homo sacien < 220 > < 221 > diverse feature < 222 > (1) ... (801) < 223 > n = A, T, C or G < 400 > 16 gccccaattc cagctgccac accacccacg gtgactgcat tagttcggat gtcatacaaa 60 agctgattga agcaaccctc tactttttgg tcgtgagcct tttgcttggt gcaggtttca 120 ttggctgtgt tggtgacgtt gtcattgcaa cagaatgggg gaaaggcact gttctctttg 180 aagtagggtg agtcctcaaa atccgtatag ttggtgaagc cacagcactt gagccctttc 240 atggtggtgt tccacacttg agtgaagtct tcctgggaac cataatcttt cttgatggca 300 gcaacgtcag ggcactacca gccattgtgg gaagtgctca ggcgaccaca tgtacaccaa 360 gcagctgcaa cctcagcaat gaagatgagg aggaggatga agaagaacgt cncgagggca 420 cacttgctct ccgtcttagc accatagcag cccangaaac caagagcaaa gaccacaacg 480 atgaaagaaa ccngctgcga ntacccacst tgacaaactg catggccact ggacgacagt 540 atcttcagaa tggcccgaan aagggatgcc ccatcgattg aacacccana tgcccactgc 600 cr.acagggct gcnccncncn gaaagaatga gccattgaag aaggatcntc ntggtcttaa 660 tgaactgaaa ccntgcatgg tggcccctgt tcagggctct tggcagtgaa ttctganaaa 720 aaggaacngc ntnagccccc ccaaangana aaacaccccc gggtgttgcc ctgaattggc ggccaaggan ccctgccccn g 801 780
< 210 > 17 < 211 > 740 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (740) < 223 > n = A, T, C or G < 400 > 17 ggcgtccctc gtgagagcca tgcctgccca ctcagtggca acacccggga gctgttttgt 60 cctttgtgga gcctcagcag ttccctcttt cagaactcac tgccaagagc cctgaacagg 120 agccaccatg cagtgcttca gcttcattaa atcctcttca gaccatgatg atttgctcat 180 ctttctgtgt ggtgcagccc tgttggcagt gggcatctgg gtgtcaatcg atggggcatc 240 ctttctgaag atcttcgggc cactgtcgtc cagtgccatg acgtgggcta cagtttgtca 300 cttcctcatc gcagccggcg ttgtggtctt tgctcttggt ttcctgggct gctatggtgc 360 taagacggag agcaagtgtg ccctcgtgac gttcttcttc atcctcctcc tcatcttcat 420 tgctgaagtt gcagctgctg tggtcgcctt ggtgtacacc acaatggctg aaccattcct 480 gacgttgctg gtantgcctg ccatcaanaa agattatggg ttcccaggaa aaattcactc 540 aantntggaa caccnccatg aaaagggctc caatttctgn tggcttcccc aactataccg - 600 gaattttgaa agantcnccc tacttccaaa aaaaaanant tgcctttncc cccnttctgt 660 tgcaatgaaa acntcccaan acngccaatn aaaacctgcc cnnncaaaaa ggntcncaaa caaaaaaant nnaagggttn 720 740
< 210 > 18 < 211 > 802 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature '< 222 > (1) ... (802) < 223 > n = A, T, C or G < 400 > 18 cgctggtcca ccgctggttg gaagcacgtc gngnagccac gcctcaatca agcatacaca 60 cagctgccgc caaggtcttc acattacgca gggcaagagc ctccagcaac actgcatatg 120 tactttagca ggatacactt gccagggtga caactgagag gtgtcgaagc ttattcttct 180 gagcctctgt tagtggagga agattccggg cttcagctaa gtagtcagcg tatgtcccat 240 aagcaaacac tgtgagcagc cggaaggtag aggcaaagtc actctcagcc agctctctaa 300 cattgggcat gtccagcagt tctccaaaca cgtagacacc agnggcctcc agcacctgat 360 ggatgagtgt ggccagcgct gcccccttgg ccgacttggc taggagcaga aattgctcct 420 ggttctgccc tgtcaccttc acttccgcac tcatcactgc actgagtgtg ggggacttgg 480 gctcaggatg tccagagacg tggttccgcc ccctcnctta atgacaccgn ccanncaacc 540 gtcggctccc gccgantgng ttcgtcgtnc ctgggtcagg gtctgctggc cnctacttgc 600 aancttcgtc nggcccatgg aattcaccnc accggaactn gtangatcca ctnnttctat 660 aaccggncgc caccgcnnnt ggaactccac tcttnttncc tttacttgag ggttaaggtc 720 acccttnncg ttaccttggt ccaaaccntn ccntgtgtcg tcnggnccna anatngtnaa 780 ng tnccanccnc atangaagcc 802
< 210 > 19 < 211 > 731 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (731) < 223 > n = A, T, C or G < 400 > 19 cnaagcttcc aggtnacggg ccgcnaancc tgacccnagg tancanaang cagncngcgg 60 gagcccaccg tcacgnggng gngtctttat nggagggggc ggagccacat cnctggacnt 120 cntgacccca actccccncc ncncantgca gtgatgagtg cagaactgaa ggtnacgtgg 180 caggaaccaa gancaaannc tgctccnntc caagtcggcn nagggggcgg ggctggccac 240 gcncatccnt cnagtgctgn aaagccccnn cctgtctact tgtttggaga acngcnnnga 300 catgcccagn gttanataac nggcngagag tnantttgcc tctcccttcc ggctgcgcan 3B0 cgngtntgct tagnggacat aacctgacta cttaactgaa cccnngaatc tnccncccct 420 ccactaagct aacttcgaca cagaacaaaa ccactcantt gtcacctgnc tgctcaagta 480 aagtgtaccc catncccaat gtntgctnga ngctctgncc tgcnttangt tcggtcctgg 540 gaagacctat caattnaagc tatgtttctg actgcctctt gctccctgna acaancnacc 600 cnncnntcca agggggggnc ggcccccaat ccccccaacc ntnaattnan tttanccccn 660 cccccnggcc cggcctttta cnancntcnn nnacngggna aaaccnnngc tttncccaac nnaatccncc 720 t 731
< 210 > 20 < 211 > 754 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (754) < 223 > n = A, T, C or G < 400 > Tttttttttt tttttttttt 20 taaaaacccc ctccattnaa tgnaaacttc cgaaattgtc 60 ceaccccctc ntccaaatnn ccntttccgg gngggggttc caaacccaan ttanntttgg 120-Tttaaatt aaatnttnnt tggnggnnna anccnaatgt nangaaagtt raacccanta 180 ^ -. Ncttnaa tncctscaaa ccngtngntt ccaaaaatnt ttaaccctta antccctccg 240 == "- gttna nggaaa = ccc aenttctcnt aaggttgttt gaaggntnaa tiaaaanccc 300 - ^ ccaattgt ttttraccac gcctgaatta attggnttcc gntgttttcc - taaaanaa 360 c, c ^ aa -ancccc ggttart tccccccnnc cccaattata ccganttttt ttngaattgg 420 -.-.- ACGG gaatta = cgg ggnnnntccc tnttgggggg cnggnrcccc ccccntcggg 480 ggttngggnc aggncnnaat tgtttaaggg tccgaaaaat ccctccnaga aaaaaanctc 540 ccaggntgag nntngggttt nccccccccc canggcccct ctcgnanagt tggggtttgg. 600 ggggcctggg attttntttc ccctnttncc tccccccccc ccnggganag aggttngngt 660 tttgntcnnc ggccccnccn aaganctttn ccganttnan ttaaatccnt gcctnggcga 720 agtcc ttgn agggntaaan ggccccctnn cggg 754
< 210 > 21 < 211 > 755 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (755) < 223 > n = A, T, C or G < 40 0 > 21 atcancccat gaccccnaac nngggaccnc tcanccggnc nnncnaccnc cggccnatca 60 nngtnagnnc actncnnttn natcacnccc cnccnactac gcccncnanc cnacgcncta 120 nncanatncc actganngcg cgangtngan ngagaaanct nataccanag ncaccanacn 180 ccagctgtcc nanaangcct nnnatacngg nnnatccaat ntgnancctc cnaagtattn 240 nncnncanat gattttcctn anccgattac ccntnccccc tancccctcc cccccaacna 300 cgaaggcnct ggnccnaagg nngcgncncc ccgctagntc cccnncaagt cncncnccta 360 aactcanccn nattacncgc ttcntgagta tcactccccg aatctcaccc tactcaactc 420 aaaaanatcn gatacaaaat aatncaagcc tgnttatnac actntgactg ggtctctatt 480 ttagnggtcc ntnaancntc ctaatacttc cagtctncct tcnccaattt ccnaanggct 540 ctttcngaca gcatnttttg gttcccnntt gggttcttan ngaattgccc ttcntngaac 600 gggctcntct tttccttcgg ttancctggn ttcnnccggc cagttattat ttcccntttt 660 aaattcntnc cntttanttt tggcnttcna aacccccggc cttgaaaacg gccccctggt 720 aaaaggttgt tttganaaaa tttttgtttt gttcc 755
< 210 > 22 < 211 > 849 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (849) < 223 > n = A, T, C or G < 40 0 > 2 tttttttttt tttttangtg tngtcgtgca ggtagaggct Tacta aant gtgaanacgt 60 acgctnggan ta ngcgacc cganttctag ganncnccct aaaa canac tgtgaagatn 120 atcctgnnna cggaanggtc accggnngat nntgctaggg tgnee.ctcc cannncnttn 180 cataaeteng nggccctgcc caccaccttc ggcggcccng ngneegggcc cgggtcattn 240 gr.r.tt aaccn falls tnngcna ncggtttccn nccccnncng aeccr.ggcga tccggggtnc 300 tctgt ettec cctgnagnen anaaantggg ccncggnccc cttta cccct nnacaageca 360 cngccnteta necncngccc cccctccant nngggggact geenar.ngct ccgttnctng 420 nnacccennn ggg necteg gttgtcgant cnacegnang ccanggatte cnaaggaagg 480 TGCG tnttg gcc ctaccc ttcgctncgg nncacccttc cegacnanga nccgctcccg 540 cncnncgnng cctcncctcg caacacccgc netcntengt ncggr.nnece ccccacccgc 600 nccctcnene ngncgnar.cn ctccnccncc gtetcannea ccaccccgcc ccgccaggcc 660 ntcanccacn ggn igacnng nagenennte gcnccgcgcn gegner.ccct cgccncngaa 720 ctncntengg ceantnncgc tcaancenna cnaaacgccg ctgcg cggcc cgnagcgncc 780 neceecnega gte CC CIP. cttccnaccc ansnnttccr. cgag:; acacn nnaccccgcc 840 cgg 849
< 210 > 23 < 211 > 872 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (872) < 223 > n = A, T, C or G < 400 > 23 gcgcaaacta tacttcgctc gnactcgtgc gcctcgctnc tcttttcctc cgcaaccatg 60 tctgacnanc ccgattnggc ngatatcnan aagntcganc agtccaaact gantaacaca 120 cacacncnan aganaaatcc nctgccttcc anagtanacn attgaacnng agaaccangc 180 nggcgaatcg taatnaggcg tgcgccgcca atntgtcncc gtttattntn ccagcntcnc 240 ctnccnaccc tacntcttcn nagctgtcnn acccctngtn cgnacccccc naggtcggga 300 tcgggtttnn nntgaccgng cnncccctcc ccccntccat nacganccnc ccgcaccacc 360 nanngcncgc nccccgnnct cttcgccncc ctgtcctntn cccctgtngc ctggcncngn 420 accgcattga ccctcgccnn ctncnngaaa ncgnanacgt ccgggttgnn annancgctg 480 tgggnnngcg tctgcnccgc gttccttccn ncnncttcca ccatcttcnt tacngggtct 540 ccncgccntc tcnnncacnc cctgggacgc tntcctntgc cccccttnac tccccccctt 600 cgncgtgncc cgnccccacc ntcatttnca nacgntcttc acaannncct ggntnnctcc 660 cnancngncn gtcanccnag ggaagggngg ggnnccnntg nttgacgttg nggngangtc 720 cgaanantcc tcnccntcan enctacccct cgggcgnnct ctcngttncc aacttancaa 780 ntctcccccg ngngcncntc tcagcctcnc ccnccccnct ctctgcantg tnctctgctc 840 tnaccnntac gantntt cgn cnccctcttt ce 872
< 210 > 24 < 211 > 815 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (815) < 223 > n = A, T, C or G < 400 > 24 gcatgcaagc ttgagtattc tatagngtca ectaaatane ttggcntaat catggtcnta 60 nctgncttcc tgtgtcaaat gtatacnaan tanatatgaa caaganngta tctnatntga 120 tcntncatta gtaacaantg tnntgtccat cctgtcngan canattccca tnnattncgn 180 cgcattcncn gencantatn taatngggaa ntcnnntnnn ncaccnncat ctatcntncc 240 gcnccctgac tggnagagat ggatnanttc tnntntgacc nacatgttca tcttggattn 300 aananccccc cgcngnccac cggttngnng cnagccnntc ccaagacctc ctgtggaggt 360 aganneatca aacctgcgtc aacntgggaa acccgcnncc angtnnaagt ngnnncanan 420 gatcccgtcc aggnttnacc atcccttcnc agcgccccct ttngtgcctt anagngnagc 480 gtgtccnanc cnctcaacat ganacgcgcc agnccanccg caattnggca caatgtcgnc 540 gggggantna gaacccccta tncaaanccc caggattgtc cnencangaa atcccncanc 600 cccnccctac ccnnctttgg gacngtgacc aantcccgga gtnccagtcc ggccngnctc 660 ccccaccggt nnccntgggg gggtgaanct cngnntcanc cngncgaggnntcgnaagga 720 accggncctn ggncgaanng anenntenga agngecnent cgtataaccc cccctcncca 780 nccnacngnt agntcccccc cngggtncgg aangg 815
< 210 > 25 < 211 > 775 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (775) < 223 > n = A, T, C or G < 400 > 25 ccgagatgtc tcgctccgtg gccttagctg tgctcgcgct actctctctt tctggcctgg 60 gcgtactcca aggctatcca aagattcagg tttactcacg tcatccagca gagaatggaa 120 agtcaaattt cctgaattgc tatgtgtctg ggtttcatcc atccgacatt gaanttgact 180 tactgaagaa tgganagaga attgaaaaag tggagcattc agacttgtct ttcagcaagg 240 actggtcttt ctatctcntg tactacactg aattcacccc cactgaaaaa gatgagtatg 300 cctgccgtgt gaaccatgtg actttgtcac agcccaagat agttaagtgg gatcgagaca 360 tgtaagcagn cnncatggaa gtttgaagat gccgcatttg gattggatga attccaaatt 420 ctgcttgctt gcnttttaat antgatatgc ntatacaccc taccctttat gnccccaaat 480 tgtaggggtt acatnantgt tcncntngga catgatcttc ctttataant ccnccnttcg 540 aattgcccgt cncccngttn ngaatgtttc cnnaaccacg gttggctccc ccaggtcncc 600 gggcctgggc tcttacggaa cnctttncaa ggttggggga accnaaaatt tcncttntgc 660 ccncccncca cnntcttgng nncncanttt ggaacccttc cnattcccct tggcctcnna 720 nccttnncta anaaaacttn aaancgtngc naaanntttn acttcccccc ttacc 775 < 210 > 26 < 211 > 820 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (820) < 223 > n = A, T, C or G < 400 > 26 anattantac agtgtaatct tttcccagag gtgtgtanag ggaacggggc ctagaggcat 60 ncttatanca cccanagata gaccaagagc acagtgcttt atttcctgca tgctgggcac 120 gaaaaggtgg cggtccccat cactcctcct ctcccatagc catcccagag gggtgagtag 180 ccatcangcc ttcggtggga gggagtcang gaaacaacan accacagagc apacagacca 240 ntgatgacca tgggcgggag cgagcctctt ccctgnaccg gggtggcana nganagccta 300 nctgaggggt cacactataa acgttaacga ccnagatnan cacctgcttc aagtgcaccc 360 ttcctacctg acnaccagng accnnnaact gcngcctggg gacagcnctg ggancagcta 420 acnnagcact cacctgcccc cccatggccg tncgcntccc tggtcctgnc aagggaagct 480 ccctgttgga attncgggga nccccctcct naccaaggga ccanctgtga aggaaaaann 540 gatggaattt tncccttccg gccnntcccc tcttccttta cacgccccct nntactcntc 600 tccctctntt ntcctgncnc acttttnacc ccnnnatttc ccttnattga tcggannctn 660 ganattccac tnncgcctnc cntcnatcng naanacnaaa nactntctna cccnggggat 720 gggnncctcg ntcatcctct ctttttcnct accnccnntt ctttgcctct ccttngatca 780 tccaaccntc gntggccntn cccccccnnn tcctttnccc 820
< 210 > 27 < 211 > 818 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > Characteristic Diversity Sa < 222 > ( 1 ) . . . (8 18) < 223 > n = A, T, C or G < 400 > 27 tctgggtga t GGCC tcttcc tt ctcaggga cctctgactg ctctgggcca to agaatctc t 60 tgtttcttct ccgagcccca ggcagcggtg attcagccct gcccaacctg attctgatga 120 ctgcggatgc tgtgacggac ccaaggggca aatagggtcc cagggtccag ggaggggcgc 180 ctgctgagca cttccgcccc tcaccctgcc cagcccctgc catgagctct gggctgggtc 240 gggttctgct tccgcctcca cttccangca ngccancaag tggcgctggg ccacactggc 300 ttcttcctgc cccntccctg gctctgantc tctgtcttcc tgtcctgtgc angcnccttg 360 gatctcagtt tccctcnctc anngaactct gtttctgann tcttcantta actntgantt 420 tatnaccnan tggnctgtnc tgtcnnactt taatgggccn gaccggctaa tccctccctc 480 nctcccttcc anttcnnnna accngcttnc cntcntctcc ccntancccg ccngggaanc 540 ctcctttgcc ctnaccangg gccnnnaccg cccntnnctn ggggggcnng gtnnctncnc 600 ctgntnnccc cnctcncnnt tncctcgtcc cnncnncgcn nngcannttc ncngtcccnn 660 ngtntcgnaa tnnctcttcn ngntcncntn tnnnnngncn ngntnntncn tccctctcnc 720 cnnntgnang tnnttnnnnc ncngnncccc nnnncnnnnn nggnnntnnn tctncncngc ^^ 780 ccc ccccc ngnattaagg cctccnntct ccggccnc 818 < 210 > 28 < 211 > 731 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (731) < 223 > n = A, T, C or G < 400 > 28 aggaagggcg gagggatatt gtangggatt gagggatagg agnataangg gggaggtgtg 60 tcccaacatg anggtgnngt tctcttttga angagggttg ngtttttann ccnggtgggt 120 gattnaaccc cattgtatgg agnnaaaggn tttnagggat ttttcggctc ttatcagtat 180 ntanattcct gtnaatcgga aaatnatntt tcnncnggaa aatnttgctc ccatccgnaa 240 attnctcccg ggtagtgcat nttngggggn cngccangtt tcccaggctg ctanaatcgt 300 actaaagntt naagtgggan tncaaatgaa aacctnncac agagnatccn tacccgactg 360 tnnnttncct tcgccctntg actctgcnng agcccaatac ccnngngnat gtcncccngn 420 nnngcgncnc tgaaannnnc tcgnggctnn gancatcang gggtttcgca tcaaaagcnn 480 cgtttcncat naaggcactt tngcctcatc caaccnctng ccctcnncca tttngccgtc 540 nggttcncct acgctnntng cncctnnntn ganattttnc ccgcctnggg naancctcct 600 gnaatgggta gggncttntc ttttnaccnn gnggtntact aatcn ^ cTnC acgcntnctt 660 tctcnacccc cccccttttt caatcccanc ggcnaatggg gtctccccnn cgangggggg nnncccannc 720 c 731 < 210 > 29 < 211 > 822 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (822) < 223 > n = A, T, C or G < 400 > 29 actagtccag tgtggtggaa ttccattgtg ttggggncnc ttctatgant antnttagat 60 cgctcanacc tcacancctc ccnacnangc ctataangaa nannaataga nctgtncnnt 120 Atnt tacnc tcatanncct cnnnacccac tccctcttaa cccntactgt gcctatngcn 180 tnnctantct ntgccgcctn cnanccaccn gtggsccnac cncrngiatt ctcnatctcc 240 tcnccatntn gcctananta ngtncatacc ctatacctac pccaatgcta nnnctaancn 300 t "~ ze -" igh-c; a ' actgacnl ngacttc ^ ca: -. = - ttcct eatttgaatc 360
_actc_gact cccac ~ gcct an.inattagc ar tntccccc rac ^ at "tct caaccaaatc <? 20 ntc caacc tatctanctg ttcrccaacc nttncctccg atccccpac aacccctc 430 cca = -taccc nccacc ^ gac ncctaacccn cacca: ccccgcea c:" a ggncatttan 5? 0 ccactggaat cacnatngga 'naaaaaaaac ccnaactctc tancncnnat ctccctaana 600 aatnctcctn naatttactn ncantnccat caancccacn tgaaacnnaa cccctgtttt 660 tanatccctt ctttcgaaaa ccnacccttt annncccaac ctttngggcc cccccnctnc 720 ccnaatgaag gncncccaat cnangaaacg nccntgaaaa ancnaggcna anannntccg 780 canatcctat cccttanttn ggggnccctt ncccngggcc ce 822
< 210 > 30 < 211 > 787 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (787) < 223 > n = A, T, C or G < 400 > 30 ctctggcaca cggccgcctg tgcctcctga atggcatcaa aagtgatgga ctgcccattg 60 ctagagaaga ccttctctcc tactgtcatt atggagccct gcagactgag ggctcccctt 120 gtctgcagga tttgatgtct gaagtcgtgg agtgtggctt ggagctcctc atetacatna 180 gctggaagcc ctggagggcc tctctcgcca gcctccccct tctctccacg ctctccangg 240 acaccagggg ctccaggcag cccattattc ccagnangac atggtgtttc tccacgcgga 300 cccatágggc ctgnaaggcc agggtctcct ttgacaccat ctctcccgtc ctgcctggca 360 ggccgtggga tecactantt ctanaacggn cgccaccncg gtgggagctc cagcttttgt 420 tcccnttaat gaaggttaat tgcncgcttg gcgtaatcat nggtcanaac tntttcctgt 480 gtgaaattgt ttntcccctc ncnattccnc nenacataen aacccggaan cataaagtgt 540 taaagcctgg gggtngcctn nngaatnaac tnaactcaat taattgcgtt ggctcatggc 600 ccgctttccn ttcnggaaaa ctgtcntccc ctgcnttnnt gaatcggcca ccccccnggg 660 aaaagcggtt tgcnttttng ggggntcctt ccncttcccc cctcnctaan ccctncgcct 720 cggtcgttnc nggtngcggg gaangggnat nnnctcccnc naagggggng agnnngntat ccccaaa 780 787
< 210 > 31 < 211 > 799 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (799) < 223 > n = A, T, C or G < 400 > 31 tttttttttt tttttttggc gatgetactg tttaattgca ggaggtgggg gtgtgtgtac 60 catgtaccag ggctattaga agcaagaagg aaggagggag ggcagagcgc cctgctgagc 120 aacaaaggac tcctgcagcc ttctctgtct gtctcttggc gcaggcacat ggggaggcct 180 cccgcagggt gggggccacc agtccagggg tgggagcact acanggggtg ggagtgggtg 240 gtggctggtn cnaatggcct gneacanate cctacgattc ttgacacctg gattteacca 300 tgttctccca ggggaccttc nggnaacttc ntnnatctcn aaagaacaca actgtttctt 360 cngcanttct ggctgttcat ggaaagcaca ggtgtccnat ttnggctggg acttggtaca 420 tatggttccg gcccacctct cccntcnaan aagtaattca cccccccccn ccntctr.ctg 480 cctgggccct taantaecca canttantta caccggaact ttcatcttng gntgggcttg 540 ntnatcncen cctgaa.gcg ccaagttgaa aggccacgcc gtncccnctc eccatagran 600 nttttnncnt canctaatgc ccccccnggc aacnatecaa tccccccccn tgggggeccc 660 agcccanggc ccccgnctcg ggnnnccngn cncgnantcc ccaggntctc ccantcr.gnc 720 cccgcacgca ccnnngcncc gaacanaagg ntngagccnc cgcannnnnn nggtnncr.ac 780 ctcgcccccc ccnncgpng 799
< 210 > 32 < 211 > 789 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (789) < 223 > n = A, T, C or G < 400 > 32 tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60 ttttnccnag ggcaggttta ttgacaacct cncgggacac aancaggctg gggacaggac 120 ggcaacaggc tccggcggcg gcggcggcgg ccctacctgc ggtaccaaat ntgcagcctc 180 cgctcccgct tgatnttcct ctgcagctgc aggatgccnt aaaacagggc ctcggccntn 240 ggtgggcacc ctgggatttn aatttccacg ggcacaatgc ggtcgcancc cctcaccacc 300 nattaggaat agtggtntta cccnccnccg ttggcncact ccccntggaa accacttntc 360 gcggctccgg catctggtct taaaccttgc aaacnctggg gccctctttt tggttantnt 420 nccngccaca atcatnactc agactggcnc gggctggccc caaaaaancn ccccaaaacc 480 ggnccatgtc ttnncggggt tgctgcnatn tncatcacct cccgggcnca ncaggncaac 540 ccaaaagttc ttgnggcccn caaaaaanct ccggggggnc ccagtttcaa caaagtcatc 600 ccccttggcc cccaaatcct ccccccgntt nctgggtttg ggaacccacg cctctnnctt 660 tggnnggcaa gntggntccc ccttcgggcc cccggtgggc ccnnctctaa ngaaaacncc 720 ntcctnnnca ccatcccccc nngnnacgnc tancaangna tccctttttt tanaaacggg ccccccncg 780 789
< 210 > 33 < 211 > 793 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (793) < 223 > n = A, T, C or G < 40 0 > 33 gacagaacat gttggatggt ggagcacctt tctatacgac ttacaggaca gcagatgggg 60 aattcatggc tgttggagca atanaacccc agttctacga gctgctgatc aaaggacttg 120 tgatgaactt gactaaagtc tgagcatgga cccaatcaga gaaatgaana tgattggcca 180 agaagtttgc agatgtattt gcaaagaaga cgaaggcaga gtggtgtcaa atctttgacg 240 ctgtgtgact gcacagatgc ccggttctga cttttgagga ggttgttcat catgatcaca 300 acaangaacg gggctcgttt atcaccantg aggagcagga cgtgagcccc cgccctgcac 360 aaacacccca ctctgctgtt gccatccctt ctttcaaaag ggatccacta cttctagagc 420 ggncgccacc gcggtggagc tccagctttt gttcccttta gtgagggtta attgcgcgct 480 tggcgtaatc atggtcatan ctgtttcctg tgtgaaattg ttatccgctc acaattccac 540 acaacatacg anccggaagc atnaaatttt aaagcctggn ggtngcctaa tgantgaact 600 nactcacatt aattggcttt gcgctcactg cccgctttcc agtccggaaa acctgtcctt 660 gccagctgcc nttaatgaat cnggccaccc cccggggaaa aggcngtttg cttnttgggg 720 cgcncttccc gctttctcgc ttcctgaant ccttcccccc ggtctttcgg cttgcggcna acggtatcna 780 793 cct
< 210 > 34 < 211 > 756 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (756) < 223 > n = A, T, C or G < 40 0 > 34 gccgcgaccg gcatgtacga gcaactcaag ggcgagtgga accgtaaaag ccccaatctt 60 ancaagtgcg gggaanagct gggtcgactc aagctagttc ttctggagct caacttcttg 120 ccaaccacag ggaccaagct gaccaaacag cagctaattc tggcccgtga catactggag 180 atcggggccc aatggagcat cctacgcaan gacatcccct ccttcgagcg ctacatggcc 240 cagctcaaat gctactactt tgattacaan gagcagctcc ccgagtcagc ctatatgcac 300 cagctcttgg gcctcaacct cctcttcctg ctgtcccaga accgggtggc tgantnccac 360 acgganttgg ancggctgcc tgcccaanga catacanacc tcnaccacca aatgtctaca 420 gtgtcctgga gcaatactga tgganggcag ctaccncaaa gtnttcctgg ccnagggtaa 480 catcccccgc cgagagctac accttcttca ttgacatcct gctcgacact atcagggatg 540 aaaatcgcng ggttgctcca gaaaggctnc aanaanatcc ttttcnctga aggcccccgg 600 atncnctagt nctagaatcg gcccgccatc gcggtgganc ctccaacctt tcgttnccct 660 ttactgaggg ttnattgccg cccttggcgt tatcatggtc acnccngttn cctgtgttga 720 aattnttaac cccccacaat tccacgccna cattng 756
< 210 > 35 < 211 > 834 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (834) < 223 > n = A, T, C or G < 400 > 35 ggggatctct anatcnacct gnatgcatgg ttgtcggtgt ggtcgctgtc gatgaanatg 60 aacaggatct tgcccttgaa gctctcggct gctgtnttta agttgctcag tctgccgtca 120 tagtcagaca cnctcttggg caaaaaacan caggatntga gtcttgattt cacctccaat 180 aatcttcngg gctgtctgct cggtgaactc gatgacnang ggcagctggt tgtgtntgat 240 aaantccanc angttctcct tggtgacctc cccttcaaag ttgttccggc cttcatcaaa 300 cttctnnaan angannancc canctttgtc gagctggnat ttgganaaca cgtcaccgtt 360 ggaaactgat cccaaatggt atgtcatcca tcgcctctgc tgcctgcaaa aaacttgctt 420 ggcncaaatc cgactccccn tccttgaaag aagccnatca cacccccctc cctggactcc 480 nncaangact ctnccgctnc cccntccnng cagggttggt ggcannccgg gcccntgcgc 540 ttcttcagcc agttcacnat nttcatcagc ccctctgcca gctgttntat tccttcgggg 600 ggaanccgtc tctcccttcc tgaannaact ttgaccgtng gaatagccgc 660 people- cent acntnctggg ccgggttcaa antccctccn ttgncnntcn cctcgggcca ttctggattt 720 nccnaacttt ttccttcccc cnccccncgg ngtttggntt tttcatnggg ccccaaetct 780 gctnttggcc antcccctgg gggcntntan cnccccctnt ggtcccntng ggee 834
< 210 > 36 < 211 > 814 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (814) < 223 > n = A, T, C or G < 400 > 36 ccjg- cgct t ccngccgcgc cccgtttcca tgacnaaggc tccc t tcang t taaa t acnn 60 ec t a g- ^ aaa; attaa tgggt tgetetac ta attacks tcata agccta cnaaccagta ccca 120 na to 4.i1.ca5: t caggecatt cctaccaaag gaagaaa GGE tggtctctcc acccce t gta 180 GGAA = ggcct gccttgta = g acaccacaat ncggctgaat ctnaagtctt gtgttt tact 240 aatggaaaaa aaaaataaac aanaggtttt gttctcatgg ctgcccaccg cagcctggca 300 ctaaaacanc ccagcgctca cttctgcttg ganaaatatt ctttgctctt ttggacatca 360 ggcttgatgg tatcactgcc acntttccac ccagctgggc ncccttcccc catntttgtc 420 antganctgg aaggcctgaa ncttagtctc caaaagtctc ngcccacaag accggccacc 480 aggggangtc ntttncagtg gatctgccaa anantacccn tatcatcnnt gaataaaaag 540 gcccctgaac ganatgcttc cancancctt taagacccat aatcctngaa ccatggtgcc 600 cttccggtct gatccnaaag gaatgttcct gggtcccant ccctcctttg ttncttacgt 660 tgtnttggac ccntgctngn atnacccaan tganatcccc ngaagcaccc tncccctggc 720 atttganttt cntaaattct ctgccctacn nctgaaagca cnattccctn ggcnccnaan 780 ggngaactca agaaggtctn ngaaaaacca cncn 814
< 210 > 37 < 211 > 760 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (760) < 223 > n = A, T, C or G < 400 > 37 gcatgctgct cttcctcaaa gttgttcttg ttgccataac aaccaccata ggtaaagcgg 60 gcgcagtgtt cgctgaaggg gttgtagtac cagcgcggga tgctctcctt gcagagtcct 120 ggtccacgca gtgtctggca atgccctttg tcactgggga aatggatgcg ctggagctcg 180 tcnaanccac tcgtgtattt ttcacangca gcctcctccg aagcntccgg gcagttgggg 240 actccactaa gtgtcgtcac actgtcgatn cancagccca ttgctqcaac ggaactgggt 300 gggctgacag gtgccagaac acactggatn ggcctttcca tggaagggcc tgggggaaat 360 cncctnancc caaactgcct ctcaaaggcc accttgcaca ccccgacagg ctagaaatgc 420 actcttcttc ccaaaggtag ttgttcttgt ncctccanca tgcccaagca aaccaaaanc 480 ttgcaaaatc tgctccgtgg gggtcatnnn taccanggtt ggggaaanaa acccggcngn 540 ganccncctt gtttgaatgc naaggnaata atcctcctgt cttgcttggg tggaanagca 600 caattgaact gttaacnttg ggccgngttc cnctngggtg gtctgaaact aatcaccgtc 660 actggaaaaa ggtangtgcc ttccttgaat tcccaaantt cccctngntt tgggtnnttt 720 ctcctctncc ctaaaaatcg tnttcccccc ccntanggcg 760
< 210 > 38 < 211 > 724 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (724) < 223 > n = A, T, C or G < 400 > Tttttttttt tttttttttt tttttttttt 38 tttttaaaaa ccccctccat tgaatgaaaa 60 cttccnaaat tgtccaaccc cctcnnccaa atnnccattt ccgggggggg gttccaaacc 120 caaattaatt ttgganttta aattaaatnt tnattngggg aanaanccaa atgtnaagaa 180 aatttaaccc attatnaact taaatncctn gaaacccntg gnttccaaaa atttttaacc 240 cttaaatccc tccgaaattg ntaanggaaa accaaattcn cctaaggctn tttgaaggtt 300 ngatttaaac ccccttnant tnttttnacc cnngnctnaa ntatttngnt tccggtgttt 360 tcctr.ttaan cntnggtaac tcccgntaat gaannnccct aanccaatta aaccgaattt 420 tttttgaatt ggaaattccn ngggaattna ccggggtttt tcccntttgg gggccatncc 480 cccnctttcg gggtttgggn ntaggttgaa tttttnnang ncccccaana ncccaaaaaa 540 aaaaaactcc caagnnttaa ttngaatntc ccccttccca ggccttttgg gaaaggnggg 600 t tntggggg ccngggantt cnttcccccn ttnccncccc ccccccnggt aaanggttat 660 n ntttggt ttttgggccc cttnanggac cttccggatn gaaattaaat ccccgggncg 720 CGCG 724
< 210 > 39 < 211 > 751 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (751) < 223 > n = A, T, C or G < 400 > 39 tttttttttt tttttctttg ctcacattta atttttattt tgattttttt taatgctgca 60 caacacaata tttatttcat ttgtttcttt tatttcattt tatttgtttg ctgctgctgt 120 tttactgaaa tttatttatt gtgagaggga acttttgtgg ccttttttcc tttttctgta 180 ggccgcctta agctttctaa atttggaaca tctaagcaag ctgaanggaa aagggggttt 240 ctcgggggaa cgcaaaatca nggaaaggtt gctttgttaa tcatgcccta tggtgggtga 300 ttaactgctt gtacaattac ntttcacttt taattaattg tgctnaangc tttaattana 360 cttgggggtt ccctccccan accaaccccn ctgacaaaaa gtgccngccc tcaaatnatg 420 tcccggcnnt cacngcngaa cnttgaaaca ngttctcatt ntccccncnc caggtnaaaa 480 ccatntttaa tgaagggtta cnccacctcc acntggcnnn gcctgaatcc tcnaaaancn 540 ccctcaancn aattnctnng ccccggtcnc gcntnngtcc cncccgggct ccgggaantn 600 cacccccnga anncnntnnc naacnaaatt ccgaaaatat tcccnntcnc tcaattcccc 660 cnnagactnt cctcnncnan cncaattttc ttttnntcac gaacncgnnc cnnaaaatgn 720 nnnncncctc cnctngtccn naatcnccan c 751
< 210 > 40 < 211 > 753 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (753) < 223 > n = A, T, C or G < 400 > 40 gtggtatttt ctgtaagatc aggtgttcct ccctcgtagg tttagaggaa acaccctcat 60 agatgaaaac ccccccgaga cagcagcact gcaactgcca agcagccggg gtaggagggg 120 csccctatgc acagctgggc ccttgagaca gcagggcttc gatgtcaggc tcgatgtcaa 180 tggtctggaa gcggcggctg tacctgcgta ggggcacacc gtcagggccc accaggaact 240 tctcaaagtt ccaggcaacn tcgttgcgac acaccggaga ccaggtgatn agcttggggt 300 cggtcataan cgcggtggcg tcgtcgctgg gagctggcag ggcctcccgc aggaaggcna 360 ataaaaggtg cgcccccgca ccgttcanct cgcacttctc naanaccatg angttgggct 420 cnaacccacc accannccgg acttccttga nggaattccc aaatctcttc gr.tcttgggc 480 ttctnctgat gccctanctg gttgcccngn atgccaanca nccccaancc ccggggtcct 540 aaancacccn cctcctcntt tcatctgggt tnttntcccc ggaccntggt t ctctcaag 600 gga.-acccata tctcnaccan tactcaccnt ncccccccnt gnnacccanc cttctanngn 660 ttcccncccg ncctctggcc cntcaaanan gcttncacna cctgggtctg ccttcccccc 720 tr.ccctatct gr.accccr.cn tttgtctcan tnt 753
< 210 > 41 < 211 > 341 < 212 DNA < 213 > Homo sapien < 400 > 41 actatatcca tcacaacaga catgcttcat cccatagact tcttgacata gcttcaaatg 60 agtgaaccca tccttgattt atatacatat atgttctcag tattttggga gcctttccac 120 ttctttaaac cttgttcatt atgaacactg aaaataggaa tttgtgaaga gttaaaaagt 180 tatagcttgt ttacgtagta agtttttgaa gtctacattc aatccagaca cttagttgag 240 tgttaaactg tgatttttaa aaaatatcat ttgagaatat tctttcagag gtattttcat 300 ttttacittt tgattaattg tgttttatat attagggtag t 341
< 210 > 42 < 211 > 101 < 212 > DNA < 213 > Homo sapien < 400 > 42 acttactgaa tttagttctg tgctcttcct tatttagtgt tgtatcataa atactttgat 60 gtttcaaaca ttctaaataa ataattttca gtggcttcat a 101
< 210 > 43 < 211 > 305 < 212 > DNA < 213 > Homo sapien < 400 > 43 tacagtctaa acatctttgt gatgtgttct taaatcacca ttccttcctg gtcctcaccc 60 tccagggtgg tctcacactg taattagagc tattgaggag tctttacagc aaattaagat 120 tcagatgcct tgctaagtct agagttctag agttatgttt cagaaagtct aagaaaccca 180 cctcttgaga ggtcagtaaa gaggacttaa tatttcatat ctacaaaatg accacaggat 240 acgagagtta tggatacaga tcctggataa ctcagagctg agtacctgcc cgggggccgc tcgaa 300 305 < 210 > 44 < 211 > 852 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (852) < 223 > n = A, T, C or G < 400 > 44 acataaatat cagagaaaag tagtctttga aatatttacg tccaggagtt ctttgtttct 60 gattatttgg tgtgtgtttt ggtttgtgtc caaagtattg gcagcttcag ttttcatttt 120 ctctccatcc tcgggcattc ttcccaaatt tatataccag tcttcgtcca tccacacgct 180 ccagaatttc tcttttgtag taatatctca tagctcggct gagcttttca taggtcatgc 240 tgctgttgtt cttcttttta ccccatagct gagccactgc ctctgatttc aagaacctga 300 agacgccctc agatcggtct tcccatttta ttaatcctgg gttcttgtct gggttcaaga 360 ggatgtcgcg gatgaattcc cataagtgag tccctctcgg gttgtgcttt ttggtgtggc 420 acttggcagg ggggtcttgc tcctttttca ctctgcaaca tatcaggtga ggaaggtgac 480 tggtggttgt catggagatc tgagcccggc agaaagtttt gctgtccaac aaatctactg 540 gttggtgtca tgctaccata tataaatagt tctngtcttt ccaggtgttc atgatggaag 600 gctcagtttg ttcagtcttg acaatgacat tgtgtgtgga ctggaacagg tcactactgc 660 actggccgtt ccacttcaga tgctgcaagt tgctgtagag gagntgcccc gccgtccctg 720 ccgcccgggt gaactcctgc aaactcatgc tgcaaaggtg ctcgccgttg atgtcgaact 780 cntggaaagg gatacaattg gcatccagct ggttggtgtc caggaggtga tggagccact 840 cccacacctg gt 852
< 210 > 45 < 211 > 234 < 212 > DNA < 213 > Homo sapien < 400 > 45 acaacagacc cttgctcgct aacgacctca tgctcatcaa gttggacgaa tccgtgtccg 60 agtctgacac catccggagc atcagcattg cttcgcagtg ccctaccgcg gggaactctt 120 gcctcgtttc tggctggggt ctgctggcga acggcagaat gcctaccgtg ctgcagtgcg 180 tgaacgtgtc ggtggtgtct gaggaggtct gcagtaagot ctatgacccg ctgt 234 < 210 > 46 < 211 > 590 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (590) < 223 > n = A, T, C or G < 400 > 46 actttttatt taaatgttta taaggcagat ctatgagaat gatagaaaac atggtgtgta 60 atttgatagc aatattttgg agattacaga ttaccaatta gttttagtaa cacagttaaa 120 tatattccaa aagaagataa aatatctaat gcanatacaa ggcaggaaaa gaaagatcaa 180 tgantataac taattgacaa tggaaaatca attttaatgt ttatccttta gaattgcaca 240 aaanaaanaa aaagctttca ttattgcagt ctanttaatt caaacagtgt taaatggtat 300 caggataaan aactgaaggg canaaagaat taattttcac ttcatgtaac ncacccanat 360 ttacaatggc ttaaatgcan ggaaaaagca gtggaagtag ggaagtantc aaggtctttc 420 tggtctctaa tctgccttac tctttgggtg tggctttgat cctctggaga cagctgccag 480 ggctcctgtt atatccacaa tcccagcagc aagatgaagg gatgaaaaag gacacatgct 540 gccttccttt gaggagactt catctcactg gccaacactc agtcacatgt 590
< 210 > 47 < 211 > 774 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (774) < 223 > n = A, T, C or G < 400 > 47 acaagggggc ataatgaagg agtggggana gattttaaag aaggaaaaaa aacgaggccc 60 tgaacagaat tttcctgnac aacggggctt caaaataatt ttcttgggga ggttcaagac 120 gcttcactgc ttgaaactta aatggatgtg ggacanaatt ttctgtaatg accctgaggg 180 cattacagac gggactctgg gaggaaggat aaacagaaag gggacaaagg ctaatcccaa 240 aacatcaaas aaaggaaggt sgcgtcatac ctcccagcct acacagttct ccagggctct 300 cctcatccct ggaggacgac agtggaggaa caactgacca tgtccccagg ctcctgtgtg 360 ctggctcctg gtcttcagcc cccagctctg gaagcccacc ctctgctgat cctgcgtggc 420 ccacactcct tgaacacaca tccccaggtt atattcctgg acatggctga acctcctatt 480 cctacttccg agatgccttg ctccctgcag cctgtcaaaa tcccactcac cctccaaacc 540 acggcatggg aagcctttct gacttgcctg attactccag catcttggaa caatccctga 600 ttccccactc cttagaggca agatagggtg gttaagagta gggctggacc acttggagcc 660 aggctgctgg cttcaaattn tggctcattt acgagctat ggaccttggg caagtnatct 720 tcacttctat gggcntcatt ttgttctacc tgcaaaatgg gggataataa tagt 774
< 212 > 48 < 211 > 124 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (124) < 223 > n = A, T, C or G < 400 > 48 canaaattga aattttataa aaaggcattt ttctcttata tccataaaat gatataattt 60 ttgcaantat anaaatgtgt cataaattat aatgttcctt aattacagct caacgcaact 120 tggt 124
< 210 > 49 < 211 > 147 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (147) < 223 > n = A, T, C or G < 400 > 49 gccgatgcta ctattttatt gcaggaggtg ggggtgtttt tattattctc tcaacagctt 60 tgtggctaca ggtggtgtct gactgcatna aaaanttttt tacgggtgat tgcaaaaatt 120 ttagggcacc catatcccaa gcantgt 147
< 210 > 50 < 211 > 107 < 212 > DNA < 213 > Homo sapien < 400 > 50 acattaaatt aataaaagga ctgttggggt tctgctaaaa cacatggctt gatatattgc 60 atggtttgag gttaggagga gttaggc _a tgttttggga gaggggt 107
< 210 > 51 < 211 > 204 < 212 > DNA < 213 > Homo sapien < 400 > 51 gtcctaggaa gtctagggga cacacgactc tggggtcacg gggccgacac acttgcacgg 60 cgggaaggaa aggcagagaa gtgacaccgt cagggggaaa tgacagaaag gaaaatcaag 120 gccttgcaag gtcagaaagg ggactcaggg cttccaccac agccctgccc cacttggcca 180 cctccctttt gggaccagca atgt 204
< 210 > 52 < 211 > 491 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (491) < 223 > n = A, T, C or G < 400 > 52 acaaagataa catttatctt ataacaaaaa tttgatagtt ttaaaggtta gtattgtgta 60 gggtattttc caaaagacta aagagataac tcaggtaaaa agttagaaat gtataaaaca 120 ggtttttaaa ccatcagaca aaacaacata ttacaaaatt agacaatcat ccttaaaaaa 180 aaaacttctt gtatcaattt cttttgttca aaatgactga cttaantatt tttaaatatt 240 tcanaaacac ttcctcaaaa attttcaana tggtagcttt canatgtnc; ctcagtccca 300 atqttgctca gataaataaa tctcgtgaga acttaccacc caccacaac: tttctggggc 360 atgcaacagt gtcttttctt tnctttttct tttttttttt ttacaggcac agaaactcat 420 caattttatt tggataacaa agggtctcca aattatattg aaaaataaat ccaagttaat 480 atcactcttg t 491 < 210 > 53 < 211 > 484 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (484) < 223 > n = A, T, C or G < 400 > 53 acataattta gcagggctaa ttaccataag atgctattta ttaar.aggtr. tatgatctga 60 gtattaacag ttgctgaagt ttggtatttt tatgcagcat tttctttttr ctttgataac 120 actacagaac ccttaaggac actgaaaatt agtaagtaaa gttcagaaat attagctgct 180 caatcaaatc tctacataac actatagtaa ttaaaacgtt aaaaaaaagt gttgaaatct 240 gcactagtat anaccgctcc tgtcaggata anactgcttt ggaacagaaa gggaaaaanc 300 agctttgant ttctttgtgc tgatangagg aaaggctgaa ttaccttgtt gcctctccct 360 aggtcnggta aatgattggc aatnccaaaa catattccaa ctcaacactt cttttccncg 420 tancttgant ctgtgtattc caggancagg cggatggaat gggccagcc; ncggatgttc 480 cant 484
< 210 > 54 < 211 > 151 < 212 > DNA < 213 > Homo sapien < 400 > 54 actaaacctc gtgcttgtga actccataca gaaaacggtg ccatccctra acacggctgg 60 ccactgggta tactgctgac aaccgcaaca acaaaaacac aaatcctttg cactggctag 120 tctatgtcct ctcaagtgcc tttttgtttg t 151
< 210 > 55 < 211 > 91 < 212 > DNA < 213 > Homo sapien < 400 > 55 acctggcttg tctccgggtg gttcccggcg ccccccacgg tcctcagaa: ggacactttc 60 gccctccagt ggatactcga gccaaagtgg t 91 < 210 > 56 < 211 > 133 < 212 > DNA < 213 > Homo sapien < 400 > 56 ggcggatgtg cgttggttat atacaaatat gtcattttat gtaagggact tgagtatact 60 tggatttttg gtatctgtgg gttgggggga cggtccagga accaataccc catggatacc 120 aagggacaac tgt 133
< 210 > 57 < 211 > 147 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (147) < 223 > n = A, T, C or G < 400 > 57 actctggaga acctgagccg ctgctccgcc tctgggatga ggtgatgcan gcngtggcgc 60 gactgggagc tgagcccttc cctttgcgcc tgcctcagag gattgttgcc gacntgcana 120 tctcantggg ctggatncat gcagggt 147
< 210 > 58 < 211 > 198 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (198) < 223 > n = A, T, C or G < 400 > 58 acagggatat aggtttnaag ttattgtnat tgtaaaatac attgaatttt ctgtatactc 60 tgattacata catttatcct ttaaaaaaga tgtaaatctt aatttttatg ccatctatta 120 atttaccaat gagttacctt gtaaatgaga agtcatgata gcactgaatt ttaactagtt 180 ttgtcttcta agtttggt 198
< 210 > 59 < 211 > 330 < 212 > DNA < 213 > Homo sapien < 400 > 59 acaacaaatg ggttgtgagg aagtcttatc agcaaaactg gtgatggcta ctgaaaagat 60 ttatcattaa ccattgaaaa tgattttaaa tgacaagtta tcaaaaactc actcaatttt 120 agcttgctaa cacctgtgct aatgggagtt aactctagag caaatatagt atcttctgaa 180 tacagtcaat aaatgacaaa gccagggcct acaggtggtt tccagacttt ccagacccag 240 cagaaggaat ctattttatc acatggatct ccgtctgtgc tcaaaatacc taatgatatt 300 tttcgtcttt attggacttc tttgaagagt 330
< 210 > 60 < 211 > 175 < 212 > DNA < 213 > Homo sapien < 400 > 60 accgtgggtg ccttctacat tcctgacggc tccttcacca acatctggtt ctacttcggc 60 gtcgtgggct ccttcctctt catcctcatc cagctggtgc tgctcatcga ctttgcgcac 120 tcctggaacc agcggtggct gggcaaggcc gaggagtgcg attcccgtgc ctggt 175
< 210 > 61 < 211 > 154 < 2 12 > DNA < 213 > Homo sapien < 400 > 61 accccacttt tcctcctgtg agcagtctgg acttctcact gctacatgat gagggtgagt 60 ggttgttgct cttcaacagt atcctcccct ttccggatct gctgagccgg acagcagtgc 120 tggactgcac agccccgggg ctccacattg ctgt 154
< 210 > 62 < 211 > 30 < 212 > DNA < 213 > Homo sapien < 400 > 62 cgctcgagcc ctatagtgag tcgtattaga 30
< 210 > 63 < 21 1 > 8 9 < 212 > DNA < 213 > Homo sapi in < 400 > 63 acaagtcatt tcagcaccct ttgctcttca aaactgacca tcttttatat ttaatgcttc 60 ctgtatgaat aaaaatggtt atgtcaagt 89
< 210 > 64 < 2 11 > 97 < 212 > DNA < 213 > Homo sapien < 400 > 64 accggagtaa ctgagtcggg acgctgaatc tgaatccacc aataaataaa ggttctgcag 60 aatcagtgca tccaggattg gtccttggat ctggggt 97
< 210 > 65 < 21 1 > 377 < 212 > DNA < 213 > Homo sapi in < 220 > < 221 > diverse feature < 222 > (1) ... (377) < 223 > n = A, T, C or G < 400 > 65 acaacaanaa ntcccttctt taggccactg atggaaacct ggaaccccct tttgatggca 60 gcatggcgtc ctaggccttg acacagcqgc tggggtttgg gctntcccaa accgcacacc 120 tctacccaca ccaaccctgg nttctggcta tgggctgtct ctgccactga acatcagggt 180 tcggtcataa r.atgaaatcc caanggggac agaggtcag agaggaagct caatgagaaa 240 ggtgctgttt gctcagccag aaaacagctg cctggcattc gccgctgaac tatgaacccg 300 tgggggtgaa ctacccccan gaggaatcat gcctgggcga tgcaanggtg ccaacaggag 360 377 gggcgggagg agcatgt
< 210 > 66 < 211 > 305 < 212 > DNA < 213 > Homo sapien f 10 < 400 > 66 acgcctttcc ctcagaattc agggaagaga ctgtcgcctg ccttcctccg ttgttgcgtg 60 agaacccgtg tgccccttcc caccatatcc accctcgctc catctttgaa ctcaaacacg 120 aggaactaac tgcaccctgg tcctctcccc agtccccagt tcaccctcca tccctcacct 180 tcctccactc taagggatat caacactgcc cagcacaggg gccctgaatt tatgtggttt 240
ttatatattt tttaataaga tgcactttat gtcatttttt aataaagtct gaagaattac 300 tgttt 305 < 210 > 67 < 211 > 385 20 < 212 > DNA < 213 > Homo sapien < 400 > 67 f actacacaca ctccacttgc ccttgtgaga cactttgtcc cagcacttta ggaatgctga 60
ggtcggacca gccacatctc ttgcccagca atgtgcaaga gacatcaggt ctgagagttc 120 cccttttaaa aaaggggact tgcttaaaaa agaagtctag ccacgattgt gtagagcagc 180 tgtgctgtgc tggagattca cttttgagag agttctcctc tgagacctga tctttagagg 240 ctgggcagtc ttgcacatga gatggggctg gtctgatctc agcactcctt agtctgcttg 300 cctctcccag ggccccagcc tggccacacc tgcttacagg gcactctcag atgcccatac 360
catagtttct gtgctagtgg accgt 385 < 210 > 68 < 211 > 73 < 212 > DNA 35 < 213 > Homo sapien < 400 > 68 acttaaccag atatattttt accccagatg gggatattct ttgtaaaaaa tgaaaataaa 60 gtttttttaa tgg 73
40 < 210 > 69 < 211 > 536 < 212 > DNA < 213 > Homo sapien 45 < 220 > < 221 > diverse feature < 222 > (1) ... (536) < 223 > n = A, T, C or G 50 < 400 > 69 actagtccag tgtggtggaa ttccattgtg ttgggggctc tcaccctcct ctcctgcagc 60 tccagctttg tgctctgcct ctgaggagac catggcccag catctgagta ccctgctgct 120 cctgctggcc accctagctg tggccctggc ctggagcccc aaggaggagg ataggataat 180
55 cccsggtggc atctataacg cagacctcaa tgatgagtgg gtacagtgtg cccttcactt 240 gagtataaca cgccatcagc aggccaccaa agatgactac tacagacgtc cgctgcgggt 300 actaagagcc aggcaacaga ccgttggggg ggtgaattac ttcttcgacg tagaggtggg 360 ccgaaccata tgtaccaagt cccagcccaa cttggacacc tgtgccttcc atgaacagcc 420 agaactgcag aagaaacagt tgtgctcttt cgagatctac gaagttccct ggggagaaca 480 gaangtccct gggtgaaatc caggtgtcaa gaaatcctan ggatctgttg ccaggc 536 < 210 > 70 5 < 21 1 > 477 < 212 > DNA < 213 > Homo sapien f < 400 > 70 10 atgaccccta acaggggccc tctcagccct cctaatgacc tccggcctag ccatgtgatt 60 tcacttccac tccataacgc tcctcatact aggcctacta accaacacac taaccatata 120 ccaatgatgg cgcgatgtaa cacgagaaag ggccaccaca cacataccaa caccacctgt 180 ccaaaaaggc cttcgatacg ggataatcct atttattacc tcaqaagttt ttttcttcgc 240 agggattttt ctgagccttt taccactcca gcctagcccc taccccccaa ctaggagggc 300
actggccccc aacaggcatc accccgctaa atcccctaga agtcccactc ctaaacacat 360 ccgtattact cgcatcagga gtatcaatca cctgagctca ccatagtcta atagaaaaca 420 accgaaacca aattattcaa agcactgctt attacaattt tactgggtct ctatttt 477 < 210 > 71 20 < 211 > 533 < 212 > DNA < 213 > Homo sapien f < 220 > 25 < 221 > diverse feature < 222 > (1) ... (533) < 223 > n = A, T, C or G < 400 > 71 30 agagctatag gtacagtgtg atctcagctt tgcaaacaca ttttctacat agatagtact 60 aggtattaat agatatgtaa agaaagaaat ataatggtaa cacaccatta gattggttta 120 tgtgatttta gtggtatttt tggcaccctt atatatgttt tccaaacttt cagcagtgat 180 attatttcca taacttaaaa agtgagtttg aaaaagaaaa tctccagcaa gcatctcatt 240 taaataaagg tttgtcatct ttaaaaatac agcaatatgt gactttttaa aaaagctgtc 300
aaataggtgt gaccctacta ataattatta gaaatacatt taaaaacatc gagtacctca 360 agtcagtttg ccttgaaaaa tatcaaatat aactcttaga gaaatgtaca taaaagaatg 420 cttcgtaatt ttggagtang aggttccctc ctcaattttg tatttttaaa aagtacatgg 480 taaaaaaaaa aattcacaac agtatataag gctgtaaaat gaagaattct gcc 533
40 < 210 > 72 < 211 > 511 f < 212 > DNA < 213 > Homo sapien 45 < 220 > < 221 > diverse feature < 222 > (1) ... (511) < 223 > n = A, T, C or G 50 < 400 > 72 tattacggaa aaacacacca cataattcaa ctancaaaga anactgcttc agggcgtgta 60 aaatgaaagg cttccaggca gttatctgat taaagaacac taaaagaggg acaaggctaa 120 aagccgcagg atgtctacac tatancaggc gctatttggg ttggctggag gagctgtgga 180 aaacatggan agattggtg: gganatcgc cgtggctatt cctcattgtt attacanagt 240
Ct 55 gaggttc gtgtgcccac tggtttgaaa accgttctnc gaatagtaca aataatgata 300 cacatgagaa ctgaaatg c ccaaacccag aaagaaagcc caactagatc ctcagaanac 360 gcttctaggg acaataaccg atgaagaaaa gatggcctcc ttgtgccccc gtctgttatg 420 attgcascr.a atttctctcc naaacccgtt cttctaagca atgatggcna aacncaggtg 480 aaatacaccc cctcttgaag naccnggagg 511 < 210 > 73 < 211 > 499 5 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > 10 different feature < 222 > (1) ... (499) < 223 > n = A, T, C or G < 400 > 73 cagtgccagc actggtgcca gtaccagtac caataacagt gccagtgcca gtgccagcac 60
cagtggtggc ttcagtgctg gtgccagcct gaccgccact ctcacatttg ggctcttcgc 120 tggccttggt ggagctggtg ccagcaccag tggcagctct ggtgcctgtg gtttctccta 180 caagtgagat tttagatatt gttaatcctg ccagtctttc tcttcaagcc agggtgcatc 240 ctcagaaacc tactcaacac agcactctag gcagccacta tcaatcaatt gaagttgaca 300 ctctgcatta aatctatttg aaaaaaaaaa ccatttctga aaaaaaaggg cggccgctcg 360
antctagagg gcccgtttaa acccgctgat cagcctcgac tgtgccttct anttgccagc 420 catctgttgt ttgcccctcc cccgntgcct tccttgaccc tggaaagtgc cactcccact 480 gtcctttcct aantaaaat 499 f < 210 > 74 25 < 211 > 537 < 212 > DNA < 213 > Homo sapien < 220 > 30 < 221 > diverse feature < 222 > (1) ... (537) < 223 > n = A, T, C or G < 400 > 74 35 tttcatagga gaacacactg aggagatact tgaagaattt ggattcagcc gcgaagagat 60 ttatcagctt aactcagata aaatcattga aagtaataag gtaaaagcta gtctctaact 320 tccaggccca cggctcaagt gaatttgaat actgcattta cagtgtagag taacacataa 180 cattgtatgc atggaaacat ggaggaacag tattacagtg tcctaccact ctaatcaaga 240 aaagaattac agactctgat tctacagtga tgattgaatt ctaaaaatgg taatcattag 300
40 ggcttttgat ttataanact ttgggtactt atactaaatt atggtagtta tactgccttc 360 cagtttgctt gatatatttg ttgatattaa gattcttgac ttatattttg aatgggttct 420 f actgaaaaan gaatgatata ttcttgaaga catcgatata catttattta cactcttgat 480 tctacaatgt agaaaatgaa ggaaatgccc caaattgtat ggtgataaaa gtcccgt 537
45 < 210 > 75 < 211 > 467 < 212 > DNA < 213 > Homo sapien 50 < 220 > < 221 > diverse feature < 222 > (1) ... (467) < 223 > n = A, T, C or G 55 < 400 > 75 cja-.r * acaaz tgttcaaaag atgcaaatga tacactactg ctgcagctca caaacacctc 60 tgcatattac acgtacttcc tcctgctcct caagtagtgt ggtctatttt gccatcatca 120 cctqctgtct gcttagaaga acggctttct gctgcaangg agagaaatca taacagacgg 180 tggcacaagg aggccatctt ttcctcatcg gttattgtcc ctagaagcgt cttctgagga 240 tctagttggg ctttctttct gggtttgggc catttcantt ctcatgtgtg tactattcta 300 tcattattgt ataacggttt tcaaaccngt gggcacncaa agaacctcac tctgtaataa 360 caatgaggaa tagccacggt gatctccagc accaaatctc tccatgttnt tccagagctc 420 ctccagccaa cccaaatagc cgctgctatn gtgtagaaca tccctgn 467
< 210 > 76 < 211 > 400 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (400) < 223 > n = A, T, C or G < 400 > 76 aagctgacag cattcgggcc gagatgtctc gctccgtggc cttagctgtg ctcgcgctac 60 tctctctttc tggcctggag gctatccagc gtactccaaa gattcaggtt tactcacgtc 120 atccagcaga gaatggaaag tcaaatttcc tgaattgcta tgtgtctggg tttcatccat 180 ccgacattga agttgactta ctgaagaatg gagagagaat tgaaaaagtg gagcattcag 240 acttgtcttt cagcaaggac tggtctttct atctcttgta ttcaccccca ctacactgaa 300 ctgaaaaaga tgagtatgcc tgccgtgtga accatgtgac tttgtcacag cccaagatng 360 ttnagtggga tcganacatg taagcagcan catgggaggt 400
< 210 > 77 < 211 > 248 < 212 > DNA < 213 > Homo sapien < 400 > 77 ctggagtgcc ttggtgtttc aagcccctgc aggaagcaga atgcaccttc tgaggcacct 60 ccagctgccc cggcggggga tgcgaggctc ggagcaccct tgcccggctg tgattgctgc 120 caggcactgt tcatctcagc ttttctgtcc ctttgctccc ggcaagcgct tctgctgaaa 180 gttcatatct ggagcctgat gtcttaacga ataaaggtcc catgctccac ccgaaaaaaa aaaaaaaa 240 248
< 210 > 78 < 211 > 201 < 212 > DNA < 213 > Homo sapien < 400 > 78 actagtccag tgtggtggaa ttccattgtg ttgggcccaa cacaatggct acctttaaca 60 tcacccagac cccgccctgc ccgtgcccca cgctgctgct aacgacagta tgatgcttac 120 tctgctactc ggaaactatt tttatgtaat taatgtatgc tttcttgttt ataaatgcct 180 gatttaaaaaaaaaaaaaaa a 201 < 210 > 79 < 211 > 552 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (552) < 223 > n = A, T, C or G < 400 > 79 aggtttttga tccttttgtt gacaacccta gacctaaact gtgtcacaqa cttctgaatg 60 tttaggcagt gctagtaatt tcctcgtaat gattctgtta tractttcct attctttart 120 ctgaagatta cctctttctt atgaagttga aaattgaggt ggataaatac aaaaaggtag 180 tgtgatagta taagtatcta agtgcagatg aaagtgtgtt atatatatcc attcaaaatt 240 atgcaagtta gtaattactc agggttaact aaattacttt aatatgctgt tgaacctact 300 ctgttccttg gctagaaaaa attataaaca agtttgggaa ggactttgtt gccaaattga 360 tgttctaaaa taatattcta gttgggctat acataaanta tggaatttta tnaagaaata 420 ttcccaggaa tatggggttc atttatgaat antacccggg anagaagttt tgantnaaac 480 cngttttggt taatacgtta atatgtcctn aatnaacaag gcntgactta tttccaaaaa 540 aaaaaaaaaa aa 552 <; 210 > 80 < 211 > 476 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (476) < 223 > n = A, T, C or G < 400 > 80 acagggattt gagatgctaa ggccccagag atcgtttgat ccaaccctct tattttcaga 60 ggggaaaatg gggcctagaa gttacagagc atctagctgg tgcgctggca cccctggcct 120 cacacagact cccgagtagc tgggactaca ggcacacagt cactgaagca ggccctgttt 180 gcaattcacg ttgccacctc caacttaaac attcttcata tgtgatgtcc ttagtcacta 240 ttcccaccca aggttaaact gaaaaggcaa cttagataaa atcttagagt actttcatac 300 tcttctaagt cctcttccag cctcactttg agtcctcctt gggggttgat aggaantntc 360 tcttggcttt ctcaataaaa tctctatcca tctcatgttt aatttggtac gcntaaaaat 420 gctgaaaaaa ttaaaatgtt ctggtttcnc tttaaaaaaa aaaaaaaaaa aaaaaa 476 < 210 > 81 < 211 > 232 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (232) < 223 > n = A, T, C or G < 400 > 81 tttttttttg tatgccntcn ctgtggngtt attgttgctg ccaccctgga ggagcccagt 60 ttcttctgta tctttctttt ctgggggatc ttcctggctc tgcccctcca ttcccagcct 120 ctcatcccca tcttgcactt ttgctagggt tggaggcgct ttcctggtag cccctcagag 180 actcagtcag cgggaataag tcctaggggt ggggggtgtg gcaagccggc ct 232
< 210 > 82 < 211 > 383 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (383) < 223 > n = A, T, C or G < 400 > 82 5 aggcgggagc agaagctaaa gccaaagccc aagaagagtg gcagtgccag cactggtgcc 60 agtaccagta ccaataacat gccagtgcca gtgccagcac cagtggtggc ttcagtgctg 120 gtgccagcct gaccgccact ctcacatttg ggctcttcgc tggccttggt ggagctggtg 180 ccagcaccag tggcagctct ggtgcctgtg gtttctccta caagtgagat tttagatatt 240 gttaatcctg ccagtctttc tcttcaagcc agggtgcatc ctcagaaacc tactcaacac 300
agcactctng gcagccacta tcaatcaatt gaagttgaca ctctgcatta aatctatttg 360 ccatttcaaa aaaaaaaaaa aaa 383 < 210 > 83 < 211 > 494 15 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > 20 different feature < 222 > (1) ... (494) < 223 > n = A, T, C or G
ctggc ttataagcga tcatgtcctc cagtattacc tcaacgagca 60 tacgc tgaagaaatt tgacccgatg ggacaacaga cctgctcagc 120 cagatgacaa ctccc atactctcga caccgaatca ccatcaagaa 180 catga cccagcaacc gcgccctgtc ctctgagggt ccttaaactg 240 cctgt tacccctcgg agactccgta accaaactct tcggactgtg 300 ttgcc agccatactc tttggcntcc agtctctcgt gcgattgat 360 caatc atggtggcat cacccatnaa gggaacacat ttganttttt 420 naccagaata attac aatgaattga nttcagaata aaaactctta 480 aaaa aaaaaaaaaa 494 < 210 > 84 35 < 211 > 380 < 212 > DNA < 213 > Homo sapien < 220 > to diverse < 400 > 84 45 gctggtagcc tatggcgtgg ccacggangg gctcctgagg cacgggacag tgacttccca 60 agtatcctgc gccgcgtctt ctaccgtccc tacctgcaga tcttcgggca gattccccag 120 gaggacatgg acgtggccct catggagcac agcaactgct cgtcggagcc cggcttctgg 180 gcacaccctc ctggggccca ggcgggcacc tgcgtctccc agtatgccaa ctggctggtg 240 gtgctgctcc tcgtcatctt cctgctcgtg gccaacatcc tgctggtcac ttgctcattg 300
50 ccatgttcag ttacacattc ggcaaagtac agggcaacag cnatctctac tgggaaggcc 360 agcgttnccg cctcatccgg 380 < 210 > 85 < 211 > 481 55 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (481) < 223 > n = A, T, C or G 5 < 400 > 85 gagttagctc ctccacaacc ttgatgaggt cgtctgcagt ggcctctcgc ttcataccgc 60 tnccatcgtc atactgtagg tttgccacca cctcctgcat cttggggcgg ctaatatcca 120 aatcaagtca ggaaactctc ccgtcnatna aacctgtggc tggttctgtc ttccgctcgg 180 10 tgtgaaagga tctccagaag gagtgctcga tcttccccac acttttgatg actttattga 240 gtcgattctg catgtccagc aggaggttgt accagctctc tgacagtgag gtcaccagcc 300 ctatcatgcc nttgaacgtg ccgaagaaca ccgagccttg tgtggggggt gnagtctcac 360 ccagattctg cattaccaga nagccgtggc aaaaganatt gacaactcgc ccaggnngaa 420 aaagaacacc tcctggaagt gctngccgct cctcgtccnt tggtggnngc gcntnccttt 480 15 t 481 < 210 > 86 < 211 > 472 < 212 > DNA 20 < 213 > Homo sapien < 220 > ica diverse 25 < 223 > n = A, T, C or G < 400 > 86 aacatcttcc tgtataatgc tgtgtaatat cgatccgatn ttgtctgctg agaattcatt 60 acttggaaaa gcaacttnaa gcctggacac tggtattaaa attcacaata tgcaacactt 120
taaacagtgt gtcaatctgc tcccttactt tgtcatcacc agtctgggaa taagggtatg 180 acctgttaaa ccctattcac gcatttttga agggcgctaa ttttttttga ttcaacatct 240 aaaaaagcaa cacaagtccg aagtaaacag ttnttaattt gttagccaat tcactttctt 300 catgggacag agccatttga tttaaaaagc aaattgcata atattgagct ttgggagctg 360 atatntgagc ggaagantag cctttctact tcaccagaca caactccttt catattggga 420
tgttnacnaa agttatgtct cttacagatg ggatgctttt gtggcaattc tg 472 < 210 > 87 < 211 > 413 < 212 > DNA Homo sapien
diverse feature < 222 > (1) ... (413) 45 < 223 > n = A, T, C or G < 400 > 87 agaaaccagt atctctnaaa acaacctctc ataccttgtg gacctaattt tgtgtgcgtg 60 tgtgtgtgcg cgcatattat atagacaggc acatcttttt tacttttgta aaagcttatg 120
50 cctctttggt atctatatct gtgaaagttt taatgatctg ccataatgtc ttggggacct 180 ttgtcttctg tgtaaatggt actagagaaa acacctatnt tatgagtcaa tctagttngt 240 atgaaggaaa tttattcgac tttccagatn acaacactna caaactctcc cttgactagg 300 aaaagcanaa ggggacaaag ctgaacatna gaaacaattn cctggtgaga aatencataa 360 acagaaattg ggtngtatat tgaaananng catcattnaa acgttttttt ttt 413
33 < 210 > 88 < 211 > 4! < 212 > DNA < 213 > Homo sapien < 220 > 5 < 221 > diverse feature < 222 > (1) ... (448)
cgcagcgggt cctctctatc tagctccagc ctctcgcctg ccccactccc cgcgtcccgc 60 gtcctagccn accatggccg ggcccctgcg cgccccgctg ctcctgctgg ccatcctggc 120 cgtggccctg gccgtgagcc ccgcggccgg ctccagtccc ggcaagccgc cgcgcctggt 180 gggaggccca tggaccccgc gtggaagaag aaggtgtgcg gcgtgcactg gactttgccg 240 tcggcnanta caacaaaccc gcaacnactt ttaccnagcn cgcgctgcag gttgtgccgc 300
cccaancaaa ttgttactng gggtaantaa ttcttggaag ttgaacctgg gccaaacnng 360 tttaccagaa ccnagccaat tngaacaatt ncccctccat aacagcccct tttaaaaagg 420 gaancantcc tgntcttttc caaatttt 448 < 210 > 89 20 < 211 > 463 < 212 > DNA < 213 > Homo sapien < 220 > 25 < 221 > diverse feature < 222 > (1) ... (463) < 223 > n = A, T, C or G < 400 > 89 30 gaattttgtg cactggccac tgtgatggaa ccattgggcc aggatgcttt gagtttatca 60 gtagtgattc tgccaaagtt ggtgttgtaa catgagtatg taaaatgtca aaaaattagc 120 agaggtctag gtctgcatat cagcagacag tttgtccgtg tattttgtag ccttgaagtt 180 ctcagtgaca agttnnttct gatgcgaagt tctnattcca gtgttttagt cctttgcatc 240 tttnatgttn agacttgcct ctntnaaatt gcttttgtnt tctgcaggta ctatctgtgg 300
tttaadaaaa tagaannact tctctgcttn gaanatttga atatcttaca tctnaaaatn 360 aattctetcc ccatannaaa acccangccc ttggganaat ttgaaaaang gntccttcnn 420 aattcnnana anttcagntn tcatacaaca naacngganc ccc 463 < 210 > 90 40 < 211 > 400 < 212 > DNA < 213 > Homo sapien < 220 > 45 < 221 > diverse feature < 222 > (1) ... (400) < 223 > n = A, T, C or G < 400 > 90 50 agggattgaa ggtctnttnt actgtcggac tgttcancca ccaactctac aagttgctgt 60 ctgtctgtaa cttccactca ccagactgta gcntnttaac tcttcataaa tagaacaaat 120 tcttcaccag tcacatcttc taggaccttt ttggattcaq ttagtataag ctcttccact 180 tcctttgtta agacttcatc tggtaaagtc ttaagttttg tagaaaggaa tttaattgct 240 cgttctctaa caatgtcctc tccttgaagt atttggctga acaacccacc tnaagtccct 300
55 ttgtgcatcc attttaaata tacttaatag ggcattggt cactaggtta aattctgcaa 360 gagtcatctg tctgcaaaag ttgcgttagt atatctgcca 400 < 210 > 91 < 211 > 480 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (480) < 223 > n = A, T, C or G < 400 > 91 gagctcggat ccaataatct ttgtctgagg gcagcacaca tatncagtgc catggnaact 60
- tctacccc acatgggagc agcatgccgt agntatataa ggtcattccc tgagtcagac 120 atgcctcttt gactaccgtg tgccagtgct ggtgattctc acacacctcc nnccgctctt tgtggaaaaa ctggcacttg nctggaacta gcaagacatc acttacaaat tcacccacga aggtgtaaca gacacttgaa aagcgactct tgcattgctt tttgtccctc cggcaccagt tgtcaatact aacccgctgg tttgcctcca tcacatttgt gatctgtagc tctggataca tctcctgaca gtactgaaga acttcttctt ttgtttcaaa agcaactctt ggtgcctgtt ngatcaggtt cccatttccc agtccgaatg ttcacatggc atatnttact tcccacaaaa < 210 > 92 < 211 > 477 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (477) < 223 > n = A, T, C or G < 400 > 92 atacagccca natcccacca cgaagatgcg cttgttgact gagaacctga tgcggtcact 60 ggtcccgctg tagccccagc gactctccac ctgctggaag cggttgatgc tgcactcctt 120 cccacgcagg cagcagcggg gccggtcaat gaactccact cgtggcttgg ggttgacggt 180 taantgcagg aagaggctga ccacctcgcg gtccaccagg augcccgact gtgcgggacc 240 tgcagcgaaa ctcctcgatg gtcatgagcg ggaagcgaat gangcccagg gccttgccca 300 gaaccttccg cctgttctct ggcgtcacct gcagctgctg ccgctnacac tcggcctcgg 360 accagcggac aaacggcgtt gaacagccgc acctcacgga tgcccantgt gtcgcgctcc 420 aggaacggcn ccagcgtgtc caggtcaatg tcggtgaanc ctccgcgggt aatggcg 477
< 210 > 93 < 211 > 377 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (377) < 223 > n = A, T, C or G < 400 > 93 gaacggctgg accttgcctc gcattgtgct gctggcagga ataccttggc aagcagctcc 60 agtccgagca gccccagacc gctgccgccc gaagctaagc ctgcctctgg ccttcccctc 120 cgcctcaat cagaaccanc agtgggagca ctgtgtttag agttaagagt gaacactgtn 180 tgattttact tgggaatttc ctctgttata tagcttttcc caatgctaat ttccaaataa 240 caacaacaaa ataacatgtt tgcctgttna gttgtataaa agtar.gtgat tctgtatr. a 300 aagaaaatat tactgttaca tatactgctt gcaanttctg tatttattgg tnctctc: gaa 360 ataaatatat tattaaa 377
< 210 > 94 < 211 > 495 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (495) < 223 > n = A, T, C or G < 400 > 94 ccctttgagg ggttagggtc cagttcccag tggaagaaac aggccaggag aantgcgtgc 60 cgagctgang cagatttccc acagtgaccc cagagccctg ggctatagtc tctgacccct 120 ccaaggaaag accaccttct ggggacatgg gctggagggc aggacctaga ggcaccaagg 180 gaaggcccca ttccggggct gttccccgag gaggaaggga aggggctctg tgtgcccccc 240 acgaggaana ggccctgant cctgggatca nacacccctt cacgtgtatc cccacacaaa 300 tgcaagctca ccaaggtccc ctctcagtcc cttccctaca ccctgaacgg ncactggccc 360 agancancca acacccaccc cccgccatgg ggaatgtnct caaggaatcg cngggcaacg 420 tggactctng tcccnnaagg gggcagaatc tccaatagan gganngaacc cttgctnana 480 aaaaaaaana aaaaa 495
< 210 > 95 < 211 > 472 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (472) < 223 > n = A, T, C or G < 400 > 95 ggttacttgg tttcattgcc aCCacttagt ggatgtcatt tagaaccatt ttgtctgctc 60 cctctggaag ccttgcgcag agcggacttt gtaattgttg gagaataact gctgaatttt 120 tagctgtttt gagttgattc gcaccactgc accacaactc aatatgaaaa ctatttnact 180 tatttattat cttgtgaaaa gtatacaatg aaaattttgt tcatactgta tttatcaagt 240 gcaatagata atgatgaaaa tatattcttt tattatgttn aattatgatt gccattatta 300 atcggcaaaa tgtggagtgt atgttctttt cacagtaata tatgcctttt gtaacttcac 360 ttggttattt tattgtaaat gaattacaaa attcttaatt taagaaaatg gtangttata 420 tttanttcan taatttcttt ccttgtttac gttaattttg aaaagaatgc at. 472
< 210 > 96 < 211 > 476 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > ca racte ràs ti ca divers a < 222 > ( 1 ) . . . (47 6) < 223 > n = A, T, C or G < 400 > 96 c tgaagcatt tct tcaaact tntctacttt tgtcattgat acct gtagta agttgacaat 60 gtggtgaaat ttcaaaatta tatgtaactt ctactagttt tact ttctcc cccaagtctt 120 tt t taactca tga tt tttac acacacaatc cagaacttat tatatagcct ctaagtcttt 180 attcttcaca gtagatgatg aaagagtcct ccagtgtctt gngcanaatg ttctagntat 240 agctggatac atacngtggg agttctataa actcatacct cagtgggact naaccaaaat 300 tgtgttagtc tcaattccta ccacactgag ggagcctccc aaatcactat attcttatct 360 gcaggtactc ctccagaaaa acngacaggg caggcttgca tgaaaaagtn acatctgcgt 420
tacaaagtct atcttcctca nangtctgtn aaggaacaat ttaatcttct agcttt 476 < 210 > 97
or sapien < 220 > < 221 > diverse feature < 222 > (1) ... (479) 15 < 223 > n = A, T, C or G < 400 > 97 actctttcta atgctgatat gatcttgagt ataagaatgc atatgtcact agaatggata 60 aaataatgct gcaaacttaa tgttcttatg caaaatggaa cgctaatgaa acacagctta 120
tcaaaactca caatcgcaaa caagtgctca tctgttgtag atttagtgta ataagactta 180 gattgtgctc cttcggatat gattgtttct canatcttgg gcaatnttcc ttagtcaaat 240 caggctacta gaattctgtt attggatatn tgagagcatg aaatttttaa naatacactt 300 gtgattatna aattaatcac aaatttcact tatacctgct atcagcagct agaaaaacat 360 natcaaagta ntnnttttta ttttgtgttt ggaantgtnn aaatgaaatc tgaatgtggg 420
ttcnatctta ttttttcccn gacnactant tnctttttta gggnctattc tganccatc 479 < 210 > 98 < 211 > 461 < 212 > DNA 30 < 213 > Homo sapien < 400 > 98 agtgacttgt cctccaacaa aaccccttga tcaagtttgt ggcactgaca atcagaccta 60 tgctagttcc tgtcatctat tcgctactaa atgcagactg gaggggacca aaaaggggca 120
tcaactccag ctggattatt ttggagcctg caaatctatt cggactttga cctacttgta 180 agtgattcag tttcctctac ggatgagaga ctggctcaag aatatcctca tgcagcttta 240 tgaagccact ctgaacacgc tggttatcta gatgagaaca gagaaataaa gtcagaaaat 300 ttacctggag aaaagaggct ttggctgggg accatcccat tgaaccttct cttaaggact 360 ttaagaaaaa ctaccacatg ttgtgtatcc tggtgccggc cgtttatgaa ctgaccaccc 420
40 tttgsaataa tcttgacgct cctgaacttg ctcctctgcg a 461 < 210 > 99 < 211 > 171 < 212 > DNA 45 < 213 > Homo sapien < 400 > 99 gtggccgcgc gcaggtgttt cctcgtaccg cagggccccc tcccttcccc aggcgtccct 60 cggcgcctct gcgggcccga ggaggagcgg ctggcgggtg gggggagtgt gacccaccct 120
50 cggtgagaaa agccttctct agcgatctga gaggcgtgcc ttgggggtac c 171 < 210 > 100 < 211 > 269 < 212 >; DNA 55 < 213 > Homo sapien < 400 > 100 csc. Tgcaac-cgcaag TCCA gat gc tgggcjccg tg cggacgaa tctgcca Gcast tggtc 60 cgactgcgac gacggcggcg gcgacagtcg ggggtcttgc 120 caggtgcagc gcgggcgcct tgacgccgca aaggctgagc gaggtcgtgt cacgtcccac gaccttgacg ccgtcgggga 180 cagccggaac agagcccggt gaagcgggag gcctcgggga gcccctcggg aagggcggcc 240 cgagagatac gcaggtgcag gtggccgcc 269 < 210 > 101 < 211 > 405 < 212 > DNA F < 213 > Homo sapien 10 < 400 > 101 tttttttttt ttttggaatc tactgcgagc acagcaggtc agcaacaagt ttattttgca 60 gctagcaagg taacagggta gggcatggtt acatgttcag gtcaacttcc tttgtcgtgg 120 ttgattggtt tgtctttatg ggggcggggt ggggtagggg aaacgaagca aataacatgg 180
agtgggtgca ccctccctgt agaacctggt tacaaagctt ggggcagttc acctggtctg 240 tgaccgtcat tttcttgaca tcaatgttat tagaagtcag gatatctttt agagagtcca 300 ctgttctgga gggagattag ggtttcttgc caaatccaac aaaatccact gaaaaagttg 360 gatgatcagt acgaataccg aggcatattc tcatatcggt ggcca 405
< 210 > 102 < 211 > 470 < 212 > DNA < 213 > Homo sapien F 25 < 400 > 102 tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60 ggcacttaat ccatttttat ttcaaaatgt ctacaaattt aatcccatta tacggtattt 120 tcaaaatcta aattattcaa attagccaaa tccttaccaa ataataccca aaaatcaaaa 180 atatacttct ttcagcaaac ttgttacata aattaaaaaa atatatacgg ctggtgtttt 240
caaagtacaa ttatcttaac actgcaaaca ttttaaggaa ctaaaataaa aaaaaacact 300 ccgcaaaggt taaagggaac aacaaattct tttacaacac cattataaaa atcatatctc 360 aaatcttagg ggaatatata cttcacacgg gatcttaact tttactcact ttgtttattt 420 ttttaaacca ttgtttgggc ccaacacaat ggaatccccc ctggactagt 470
33 < 210 > 103 < 211 > 581 < 212 > DNA < 213 > Homo sapien 40 < 400 > 103 tttttttttt ttttttttga cccccctctt ataaaaaaca agttaccatt ttattttact 60
F tacacatatt tattttataa ttggtattag atattcaaaa ggcagctttt aaaatcaaac 120 taaatggaaa ctgccttaga tacataattc ttaggaatta gcttaaaatc tgcctaaagt. 180 gaaaatcttc tctagctctt ttgactgtaa atttttgact cttgtaaaac atccaaattc 240
45 atttttcttg tctttaaaat tatctaatct ttccattttt tccctattcc aagtcaattt 300 gcttctctag cctcatttcc tagctcttat ctactattag taagtggctt ttttcctaaa 360 ggaagagaaa agggaaaaca tggcacacaa aacaaacatt ttatattcat atttctacct 420 aatagcattt acgttaataa tgtgaagcca gctcaaaaga aggcttagat ccttttatgt 480 cactaaacga ccattttagt tatcaaagtg ccagaatgca aaaggtttgt gaacatttat 540
50 tcaaaagcta atataagata tttcacatac tcatctttct g 581 < 210 > 104 < 211 > 578 < 212 > DNA 33 < 213 > Homo sapien < 400 > 104 tttttttttt tttttttttt tttttctctt cttttttttt gaaatgagga tcgagttttt 60 cactctctag atagggcatg aagaaaactc atctttccag ctttaaaata acaatcaaat 120 ctcttatgct atatcatatt ttaagttaaa ctaatgagtc actggcttat cttctcctga 180 aggaaatctg ttcattcttc tcattcatat agttatatca agtactacct tgcatattga 240 gaggtttttc ttctctattt acacatatat ttccatgtga atttgtatca aacctttatt 300 ctagaaaata ttcatgcaaa atgtttcttt tgcataagag aagagaacaa tatagcatta 360 caaaactgct caaattgttt gttaagttat ccattataat tagttggcag gagctaatac 420 aaatcacatt tacgacagca ataataaaac tgaagtacca gttaaatatc caaaataatt 480 aaaggaacat ttttagcctg ggtataatta gctaattcac tttacaagca tttattagaa 540 tgaattcaca tgttattatt cctagcccaa cacaatgg 578 < 210 > 105 < 211 > 538 < 212 > DNA < 213 > Homo sapien < 400 > 105 tttttttttt tttttcagta ataatcagaa caatatttat ttttatattt aaaattcata 60 gaaaagtgcc ttacatttaa taaaagtttg tttctcaaag tgatcagagg aattagatat 120 ccaatattaa gtcttgaaca tttgaggaaa atacaccaaa atacattaag taaattattt 180 aagatcatag agcttgtaag ugaaaagata aaatttgacc tcagaaactc tsagcattaa 240 ttagcaaata aaatccacta aattactatg gacttcttgc tttaattttg tgatgaatat 300 ggggtgtcac tggtaaacca acacattctg aaggatacat tacttagtga tagattctta 360 tgtactttgc taatacgtgg atatgagttg acaagtttct ctttcttcaa tcttttaagg 420 ggcgagaaat gaggaagaaa agaaaaggat tacgcatact gttctttcta tggaaggatt 480 agatatgttt cctttgccaa tattaaaaaa ataataatgt ttactactag tsaaaccc 538
< 210 > 106 < 211 > 473 < 212 > DNA < 213 > Homo sapien < 400 > 106 tttttttttt ttttttagtc aagtttctat ttttattata attaaagtct tggtcatttc 60 atttattagc tctgcaactt acatatttaa attaaagaaa cgttttagac aactgtacaa 120 taaggtgcca tttataaatg ttattgagta atatattcct ccaagagtgg atgtgtccct 180 tctcccacca actaatgaac agcaacatta gtttaatttt attagtagat atacactgct 240 gcaaacgcta attctcttct ccatccccat gtgatattgt gratatgtgt cagttggtag 300 aatgcatcac aatctacaat caacagcaag atgaagctag gctgsgcttt c gtgaaaat 360 agactgtgtc tgtctgaatc aaatgatctg acctatcctc attcttcgaa ggtggcaaga 420 ccgcttcctc aaaggcgctg ccacatttgt ggctctttgc acttgtttca aaa 473
< 210 > 107 < 211 > 1621 < 212 > DNA < 213 > Homo sapien < 400 > 107 cgccatggca ctgcagggca tctcggtcat ggaactgtcc ggcctggccc cgggcccgtt 60 ctgtgctatg gtcctggctg acttcggggc gcgtgtggta cgcgtggacc ggcccggctc 120 ccgctacgac gtgagccgct tgggccgggg caagcgctcg ctagtgctgg atctgaagca 180 gccgcgggga gccgccgtgc tgcggcgtct gtgcaagcgg tcggatgtgc tgctggagcc 240 cttccgccgc ggtgtcatgg agaaactcca gctgggccca gagattctgc agcgggaaaa 300 atttatgcca tccaaggctt ggctgagtgg atttggccag tcaggaasct tctgccggtt 360 agctegccac gatatcaact atttggcttt gtcaggtgtt ctctcaaaaa ttggcagaag 420 TGGT agaat ccgtatgccc cgctgaatct cctggctgac ttt ctggtg tggccttat 480 ggcattataa gzgtgcactg tggctctttt tgaccgcaca cgcactgaca agggtcaggt 540 cattgatgca aatatggtgg aaggaacagc atatttaagt tcttttctst ggaaaactca 600 gaaatcgagt ctgtgggaag cacctcgagg acagaacatg TTGG = tgt-tg ragcaccttt 660 tzatacgact tacaggacag cagatgggga attcatggc gttggagt = a tagaacccca 720 gttctacgag ctgctgatca aaggacttgg actaaagtc gatgaacttc ttaatcagat 780 gagcatggat gattsgccag aaatgaagaa gaagtttgca gatgtatttg caaagaagac 840 gaaggcagag tggtgtcaaa tctttgacgg cacagatgcc tgtgtgactc cggttctgac 900 ttttgagg ag gttgttcatc atgatcacaa caaggaacgg ggctcgttta tcaccagtga 960 ggagcaggac gtgagccccc gccctgcacc tctgctgtta aacaccccag ccatcccttc 1020 gatcctttca tttcaaaagg taggagaaca cactgaggag atacttgaag aatttggatt 1080 cagccgcgaa gagatttatc agcttaactc agataaaatc attgaaagta ataaggtaaa 1140 agctagtctc taacttccag gcccacggct caagtgaatt tgaatactgc atttacagtg 1200 tagagtaaca cataacattg tatgcatgga aacatggagg aacagtatta cagtgtccta 1260 ccactctaat caagaaaaga attacagact ctgattctac agtgatgatt gaattctaaa 1320 aatggttatc attagggctt ttgatttata aaactttggg tacttatact aaattatggt 1380 agttattctg ccttccagtt tgcttgatat atttgttgat attaagattc ttgacttata 1440 ttttgaatgg gttctagtga aaaaggaatg atatattctt gaagacatcg atatacattt 1500 atttacactc ttgattctac aatgtagaaa atgaggaaat gccacaaatt gtatggtgat aaaaaaaaaa aaaaaaaaaa 1560 aaaaaaaaaa tgaaacaaaa aaaagtcacg aaaaaaaaaa 1620-1621
< 210 > 108 < 211 > 382 < 212 > PRT < 213 > Homo sapien < 400 > 108 Met Ala Leu Gln Gly Lie Ser Val Met Glu Leu Ser Gly Leu Ala Pro 1 5 10 15 Gly Pro Phe Cys Ala Met Val Leu Wing Asp Phe Gly Wing Arg Val Val 20 25 30 Arg Val Asp Arg Pro GlySer Arg Tyr Asp Val Ser Arg Leu Gly Arg 35 40 45 Gly Lys Arg Ser Leu Val Leu Asp Leu Lys Gln Pro Arg Gly Wing Wing 50 55 60 Val Leu Arg Arg Leu Cys Lys Arg Ser Asp Val Leu Leu Glu Pro Phe 65 70 75 80 Arg Arg Gly Val Met Glu Lys Leu Gln Leu Gly Pro Glu He Leu Gln 85 90 95 Arg Glu Asn Pro Arg Leu lie Tyr Wing Arg Leu Ser Gly Phe Gly Gln 100 105 110 Ser Gly Ser Phe Cys Arg Leu Wing Gly His Asp He Asn Tyr Leu Wing 115 120 125 Leu Ser Gly Val Leu Ser Lys He Gly Arg Ser Gly Glu Asn Pro Tyr 130 135 140 Wing Pro Leu Asn Leu Leu Wing Asp Phe Wing Gly Gly Gly Leu Met Cys 145 150 155 160 Wing Leu Gly He He MetAla Leu Phe Asp Arg Thr Arg Thr Asp Lys 165 170 175 Gly Gln Val He Asp Ala.Asn Met Val Glu Gly Thr Ala Tyr Leu Ser 180 185 190 Ser Phe Leu Trp Lys Th Gln Lys Ser Ser Leu Trp Glu Ala Pro Arg 195 200 205 Gly Gl n Asn Met Leu Asp Gly Gly Wing Pro Phe Tyr Thr Thr Tyr Arg 210 215 220 Thr Wing Asp Gly Glu Phe Met Wing Val Gly Wing He Glu Pro Gln Phe 225 230 235 240 Tyr Glu Leu Leu He Lys Gly Leu Gly Leu Lys Ser Asp Glu Leu Pro 245 250 255 Asn Gln Met Ser Met Asp.Asp Trp Pro Glu Met Lys Lys Lys Phe Wing 260 265 270 Asp Val Phe Wing Lys Lys Thr Lys Wing Glu Trp Cys Gln He Phe Asp 275 280 285 Gly Thr Asp Wing Cys Val Thr Pro Val Leu Thr Phe Glu Glu Val Val 290 295 300 His His Aso His Asn Lys Glu Arg Gly Ser Phe He Tbr Ser Glu G_u 30- "310 315 320 Gln Asp Val Ser Pro Arg Pro Pro Leu Leu Leu Asn Thr Pro .Ala 325 330 335 He Pro Ser Phe Lys Arg Asp Pro Phe He Gly Glu His Thr Glu Glu 340 345 350 He Leu Glu Glu Phe Gly Phe Ser Arg Glu Glu He Tyr Gln Leu Asn 355 360 365 Be Asp Lys He He Glu Ser Asn Lys Val Lys Ala Ser Leu 370 375 380
< 210 > 109 < 211 > 1524 < 212 > DNA < 213 > Homo sapien < 400 > 109 ggcacgaggc tgcgccaggg cctgagcgga ggcgggggca cctcgccag cgggggcccc 60 gggcctggcc atgcctcact gagccagcgc ctgcgcctct acctcgccga cagctggaac 120 cagtgcgacc tagtggctct cacctgcttc ctcctgggcg tgggctgccg gctgaccccg 180 ggtttgtacc acctgggccg cactgtcctc tgcatcgact tcatggtttt cacggtgcgg 240 ctgcttcaca tcttcacggt caacaaacag ctggggccca agatcgtcat cgtgagcaag 300 atgatgaagg acgtgttctt cttcctcttc ttcctcggcg tgtggctggt agcctatggc 360 gtggccacgg aggggctcct gaggccacgg gacagtgact tcccaagtat cctgcgccgc 420 gtcttctacc gtccctacct gcagatcttc gggcagattc cccaagagga catggacgtg 480 gccctcatgg agcacagcaa ctgctcgtcg gagcccggct tctgggcaca ccctcctggg 540 gcccaggcgg gcacctgcgt ctcccagtat gccaactggc tggtggtgct gctcctcgtc 600 atcttcctgc tcgtggccaa catcctgctg gtcaacttgc tcattgccat attcagttac 660 acattcggca aagtacaggg caacagcgat ctctactgga aggcgcagcg ttaccgcctc 720 atccgggaat tccactctcg gcccgcgctg gccccgccct ttatcgtcat ctcccacttg 780 cgcctcctgc tcaggcaatt gtgcaggcga ccccggagcc cccagccgtc etccccggcc 840 ctcgagcatt tccgggt tta cctttctaag gaagccgagc ggaasctgct aacgtgggaa 900 tcggtgcata aggagaactt tctgctggca cgcgctaggg acaagcggga gagcgactcc 960 gagcgtctga agcgcacgtc ccagaaggtg gacttggcac tgaaacagct gggacacatc 1020 cgcgagtacg aacagcgcct gaaagtgctg gagcgggagg tccagcagtg tagccgcgtc 1080 ctggggtggg tggccgaggc cctgagccgc tctgccttgc tgcccccagg tgggccgcca 1140 ccccctgacc tgcctgggtc caaagactga gccctgctgg cggacttcaa ggagaagccc 1200 ccacagggga ttttgctcct agagtaaggc tcatctgggc ctcggccccc gcacctggtg 1260 gccttgtcct tgaggtgagc cccatgtcca tctgggccac tgtcaggacc acctttggga 1320 gtgtcatcct tacaaaccac agcatgcccg gctcctccca gaaccagtcc cagcctggga 1380 ggatcaaggc ctggatcccg ggccgttatc catctggagg ctgcagggtc cttggggtaa 1440 agacccctca cagggaccac ccactcacag attcctcaca ctggggaaat aaagccattt 1500 aaaaaaaaaa cagaggaaaa yyyy 1524
< 210 > 110 < 211 > 3410 < 212 > DNA < 213 > Homo sapien < 400 > 110 gggaaccagc ctgcacgcgc tggctccggg tgacagccgc gcgcctcggc caggatctga 60 gtgatgagac gtgtccccac tgaggtgccc cacagcagca ggtgttgagc atgggctgag 120 aagctggacc ggcaccaaag ggctggcaga aatgggcgcc tggctgattc ctaggcagtt 180 ggcggcagca aggaggagag gccgcagctt ctggagcaga gccgagacga agcagttctg 240 gagtgcctga acggccccct gagccctacc cgcctggccc actatggtcc agaggctgtg 300 ggtgagccgc ctgctgcggc accggaaagc ccagctcttg ctggtcaacc tgctaacctt 360 tggcctggag gtgtgtttgg ccgcaggcat cacctatgtg ccgcctctgc tgctggaagt 420 gggggtagag gagaagttca tgaccatggt gctgggcatt ggtccagtgc tgggcctggt 480 ctgtgtcccg ctcctaggct cagccagtga ccactggcgt ggacgctatg gccgccgccg 540 gcccttcatc tgggcactgt ccttgggcat cctgctgagc ctctttctca tcccaagggc 600 cggctggcta gcagggctgc tgtgcccgga tcccaggccc ctagagctgg cactgctcat 660 cctgggcgtg gggctgctgg acttctgtgg ccaggtgtgc ttcactccac tggaggccct 720 gc ctctgac ctcttccggg acccggacca ctgtcgccag gcctactctg tctatgcctt 780 catgatcagt cttgggggct gcctgggcta cctcctgcct gccattgact gggacaccag 840 tgccctggcc ccctacctgg gcacccagga ggagtgcctc tttggcctgc tcaccctcat 900 cttcctcacc tgcgtagcag ccacactgct ggtggctgag gaggcagc gc tgggccccac 960 cgagccagca gaagggctgt cggccccctc cttgtcgccc cactgctgtc catgccgggc 1020 ccgcttggct ttccggaacc tgggcgccct gcttccccgg ctgcaccagc tgtgctgccg 1080 catgccccgc accctgcgcc ggctcttcgt ggctgagctg tgcagctgga tggcactcat 1140 ctgttttaca gaccttcacg cggatttcgt gggcgagggg ctgtaccagg gcgtgcccag 1200 agctgagccg ggcaccgagg cccggagaca ctatgatgaa ggcgttcgga tgggcagcct 1260 ggggctgttc ctgcagtgcg ccatctccct ggtcttctct ctggtcatgg accggctggt 1320 gcagcgattc ggcactcgag cagtctattt ggccagtgtg gcagctttcc ctgtggctgc 1380
F cggtgccaca tgcctgtccc acagtgtggc cgtggtgaca gcttcagccg ccctcaccgg 1440
gttcaccttc tcagccctgc agatcctgcc ctacacactg gcctccctct accaccggga 1500 ttcctgccca gaagcaggtg ggacactgga aataccgagg ggtgctagca gtgaggacag 1560 cctgatgacc agcttcctgc caggccctaa gcctggagct cccttcccta atggacacgt 1620 gggtgctgga ggcagtggcc tgctcccacc tccacccgcg ctctgcgggg cctctgcctg 1680 tgatgtctcc gtacgtgtgg tggtgggtga gcccaccgag gccagggtgg ttccgggccg 1740
gggcatctgc ctggacctcg ccatcctgga tagtgccttc ctgctgtccc aggtggcccc 1800 atccctgttt atgggctcca ttgtccagct cagccagtct gtcactgcct atatggtgtc 1860 tgccgcaggc ctgggtctgg tcgccattta ctttgctaca caggtagtat ttgacaagag 1920 cgacttggcc aaatactcag cgtaqaaaac ttccagcaca ttggggtgga gggcctgcct 1980 cactgggtcc cagctccccg ctcctgttag ccccatgggg ctgccgggct ggccgccagt 2040
ttctgttgct gccaaagtaa tgtggctctc tgctgccacc ctgtgctgct gaggtgcgta 2100 gctgcacagc tgggggctgg ggcgtccctc tcctctctcc ccagtctcta gggctgcccg 2160 actggaggcc ttccaagggg gtttcagtct ggacttatac agggaggcca gaagggctcc 2220 atgcactgga atgcggggac tctgcaggtg gattacccag gctcagggtt aacagctagc 2280 ctcctagttg agacacacct agagaagggt ttttgggagc tgaataaact cagtcacctg 2340
gtttcccatc tctaagcccc ttaacctgca gcttcgttta atgtagctct tgcatgggag 2400 tttctaggat gaaacactcc tccatgggat ttgaacatat gacttattta taggggaaga 2460 gtcctgaggg gcaacacaca agaaccaggt cccctcagcc cacagcactg tctttttgct 2520 gatccacccc cctcttacct tttatcagga tgtggcctgt tggtccttct gttgccatca 2580 ggcatttaaa cagagacaca tatttaactt atttatttaa caaagtagaa gggaatccat 2640
tgctagcttt tctgtgttgg tgtctaatat ttgggtaggg tgggggatcc ccaacaatca 2700 ggtcccctga gatagctggt cattgggctg atcattgcca gaatcttctt ctcctggggt 2760 ctggcccccc aaaatgccta acccaggacc ttggaaattc tactcatccc aaatgataat 2820 tccaaatgct gttacccaag gttagggtgt tgaaggaagg tagagggtgg ggcttcaggt 2880 tccctaacca ctcaacggct cccctcttct cttggcccag cctggttccc cccacttcca 2940 ctcccctcta ctctctctag gactgggctg atgaaggcac tgcccaaaat ttcccctacc 3000 cccaactttc ccctaccccc aactttcccc accagctcca caaccctgtt tggagctact 3060 gcaggaccag aagcacaaag tgcggtttcc caagcctttg tccatctcag cccccagagt 3120 atatctgtgc ttggggaatc tcacacagaa actcaggagc accccctgcc tgagctaagg 3180 gaggtcttat ctctcagggg gggtttaagt gccgtttgca ataatgtcgt cttatttatt 3240
40 tagcggggtg aatattttat actgtaagtg agcaatcaga gtataatgtt tatggtgaca 3300 aaaaaaaaaa aaaaaaaaaa ctttcttata aaattaaagg tgtttaaaaa aaaaaaaaaa aaaaaaaaaa 3360 aaaaaaaaaa aaaaaaaaaa aaaaaaaara aaaaaaataa 3410 < 210 > 111 45 < 211 > 1289 < 212 > DNA < 213 > Homo sapien < 40 0 > 111 50 agccaggcgt ccctctgcct gcccactcag tggcaacacc cgggagctgt tttgtccttt 60 gtggagcctc agcagttccc tctttcagaa agagccctga ctcactgcca acaggagcca 120 ccatgcagtg cttcagcttc attaagacca tgatgatcct cttcaatttg ctcatctttc 180 tgtg ggtgc agccctgttg gcagtgggca tctgggtgtc aatcgatggg gcatcctttc 240 tgaagatctt cgggccactg tcgtccagtg ccatgcagtt tgtcaacgtg ggctacttcc 300
55 tcatcgcagc cggcgttgtg gtctttgctc ttggtttcct gggctgctat ggtgctaaga 360 agcaa CTGA gtgtgccctc gtgacgttct tcttcatcct cctcctcatc ttcattgctg AGGT 420 tgcagc tgctgtggtc gccttggtgt acaccacaat ggctgagcac ttcctgacgt 480 XX ggtagt gcctgccatc aagaaagatt atggttccca ggaagacttc actcaagtgt 540 gsaacaccac catgaaaggg ctcaagtgct gtggcttcac caac atacg gattttgagg 600
60 actcacccta cttcaaagag aacagtgcct ttcccccatt ctgttgcaat gacaacgtca 660 ccaacacagc caatgaaacc tgcaccaagc aaaaggctca cgaccaaaaa gtagagggtt 720 gcttcaatca gcttttgtat gacatccgaa ctaatgcagt caccgtgggt ggtgtggcag 780 ctgsaattsq gggcctcgag ctggctgcca tgattgtgtc catstatctg tactgcaatc 840 tacaataagt ccacttctgc ctctgccact actgctgcca catgggaact gtgaagaggc 900 gcagcagtga accctggcaa ttgggggagg ggacaggatc taacaatgtc acttgggcca 960 gaatggacct gccctttctg ctccagactt ggggctagat agggaccact ccttttagcg 1020 atscctgact ttccttccat tggtgggtgg atgggtgggg ggcattccag agcctctaag 1080 gtagccagtt ctgttgccca ttcccccagt ctattaaacc cttgatatgc cccctaggcc 1140 tagtggtgat cccagtgctc tactggggga tgagagaaag gcattttata gcctgggcat 1200 aagtgaaatc agcagagcct ctgggtggat gtgtagaagg cacttcaaaa tgcataaacc ttaaaaaaaa 1260 1289 <tgttacaatg aaaaaaaaa; 210 > 112 < 211 > 315 < 212 > PRT < 213 > Homo sapien < 400 > 112 Met Val Phe Thr Val Arg Leu Leu His He Phe Thr Val Asn Lys Gln 1 5 10 15 Leu Gly Pro Lys He Val He Val Ser Lys Met Met Lys Asp Val Phe 20 25 30 Phe Phe Leu Phe Phe Leu Gly Val Trp Leu Val Ala Tyr Gly Val Ala 35 40 45 Thr Glu Gly Leu Leu Arg Pro Arg Asp Ser Asp Phe Pro Ser He Leu 50 55 60 Arg Arg Val Phe Tyr Arg Pro Tyr Leu Gln He Phe Gly Gln He Pro 65 70 75 80 Gln Glu Asp Met Asp ValAla Leu Met Glu His Ser Asn Cys Be Ser 85 90 95 Glu Pro Gly Phe Trp Wing His Pro Pro Gly Wing Gln Wing Gly Thr Cys 100 105 110 Val Ser Gln Tyr Wing AsnTrp Leu Val Val Leu Leu Val He Phe 115 120 125 Leu Leu Val Wing Asn He Leu Leu Val Asn Leu Leu He Wing Met Phe 130 135 140 Ser Tyr Thr Phe Gly Lys Val Gln Gly Asn Ser Asp Leu Tyr Trp Lys 145 150 155 160 Wing Gln Arg Tyr Arg Leu He Arg Glu Phe His Ser Arg Pro Wing Leu 165 170 175 Wing Pro Pro Phe He Val He Ser His Leu Arg Leu Leu Arg Gln 180 185 190 Leu Cys Arg Arg Pro Arg Ser Pro Gln Pro Ser Ser Pro Ala Leu Glu 195 200 205 His Phe Arg Val Tyr Leu Ser Lys Glu Wing Glu Arg Lys Leu Leu Thr 210 215 220 Trp Glu Ser Val His Lys Glu Asn Phe Leu Leu Wing Arg Wing Arg Asp 225 230 235 240 Lys Arg Glu Ser Asp Ser Glu Arg Leu Lys Arg Thr Ser Gln Lys Val 245 250 255 Asp Leu Ala Leu Lys Gln Leu Gly His He Arg Glu Tyr Glu Gln Arg 260 265 270 Leu Lys Val Leu Glu Arg Glu Val Gln Gln Cys Ser Arg Val Leu Gly 275 280 285 Trp Val Ala Glu Ala Leu Ser Arg Be Ala Leu Leu Pro Pro Gly Gly 290 295 300 Pro Pro Pro Asp Leu Pro Gly Ser Lys Asp 305 310 315 < 210 > 113 < 211 > 553 < 212 > PRT < 213 > Homo sapien < 400 > 113 Met Val Gln Arg Leu Trp Val Ser Arg Leu Leu Arg His Arg Lys Wing 1 5 10 15 Leu Val Asn Leu Leu Thr Phe Gly Leu Glu Val Lys Leu 20 25 30 Wing Wing Gly He Thr Tyr Val Pro Pro Leu Leu Leu Glu Val Gly Val 35 40 45 Glu Glu Lys Phe Met Thr Met Val Leu Gly He Gly Pro Val Leu Gly
50 55 60 Leu Val Cys Val Pro Leu Leu Gly Be Ala Be Asp His Trp Arg Gly 65 70 75 80
Arg Tyr Gly Arg Arg Arg Pro Phe He Trp Wing Leu Ser Leu Gly He
85 90 95
Leu Leu Ser Leu Phe Leu He Pro Arg Wing Gly Trp Leu Wing Gly Leu 100 105 110 Leu Cys Pro Asp Pro Arg Pro Leu Glu Leu Wing Leu Leu He Leu Gly 115 120 125 Val Gly Leu Leu Asp Phe Cys Gly Gln Val Cys Phe Thr Pro Leu Glu
130 135 140 Ala Leu Leu Ser Asp Leu Phe Arg Asp Pro Asp His Cys Arg Gln Ala 145 150 155 160
Tyr Ser Val Tyr Ala Phe Met He Ser Leu Gly Gly Cys Leu Gly Tyr
165 170 175
Leu Leu Pro Wing Asp Trp Asp Thr Ser Wing Leu Wing Pro Tyr Leu 180 185 190 Gly Thr Gln Glu Glu Cys Leu Phe Gly Leu Leu Thr Leu He Phe Leu 195 200 205 Thr Cys Val Wing Wing Thr Leu Leu Val Wing Glu Glu Ala Ala Leu Gly
210 215 220 Pro Thr Glu Pro Wing Glu Gly Leu Ser Wing Pro Ser Leu Ser Pro His 225 230 235 240
Cys Cys Pro Cys Arg Ala Arg Leu Ala Phe Arg Asn Leu Glv Ala Leu
245 250 255
Leu Pro Arg Leu His Gln Leu Cys Cys Arg Met Pro Arg Thr Leu Arg 260 265 270 Arg Leu Phe Val Wing Glu Leu Cys Ser Trp Met Wing Leu Met Thr Phe 275 280 285 Tnr i4? U Phe Tyr Thr Asp Phe Val Gly Glu Gly Leu Tyr Gln Gly Val
290 295 300 Pro Arg Wing Glu Pro Gly Tnr Glu Wing Arg Arg His Tyr Asp Glu Gly 305 310 315 320
Val Arg Met Gly Ser Leu Gly Leu Phe Leu Gln Cys Ala He Ser Leu
325 330 335
Val Phe be Leu Val as As Arg Leu Val Gln Arg Phe Gly Thr Arg 340 345 350 Wing Val Tyr Leu Wing Val Val Ala Wing Phe Pro Val Wing Wing Gly Wing 355 360 365 Thr Cys Leu Ser His Val Val Wing Val Val Thr Wing Be Ala Ala Leu
370 375 380 Thr Gly Pne Thr Phe Ser Ala Leu Gln He Leu Pro Tyr Thr Leu Ala 385 390 395 400
Ser Leu Tyr His Arg Glu Lys Gln Val Phe Leu Pro Lys Tyr Arg Gly
405 410 415
Asp Thr Gly Gly Wing Ser Ser Glu Asp Ser Leu Met Thr Ser Phe Leu 420 425 430 Pro Gly Pro Lys Pro G ± and Wing Pro Phe Pro Asn Gly His Val Gly Wing 435 440 445 Gly Gly Ser Gly Lea Leu Pro Pro Pro Pro Wing Leu Cys Gly Wing Ser S ^ 455 460 Wing Cys Asp Val Ser Val Val Val Val Gly Glu Pro Thr Glu Wing 465 470 7580
Arg Val Val Pro Glv »rg Giy He Cys Leu Asp Leu Ala He Leu Asp
485.90 495
Being Wing Phe Leu Lea Being G_n Val Wing Pro Being Leu Phe Met Gly Ser 500 505 510 He Val Gln Leu Ser Gln Ser Val Thr Wing Tyr Met Val Wing Wing 515 520 525 Gly Leu Gly Leu Val Wing He Tyr Phe Wing Thr Gln Val Val Phe Asp 530 535 540 Lys Se r Asp Leu Ala Lys Tyr Ser Ala 545 550 < 210 > 114 < 211 > 241 < 212 > PRT < 213 > Homo sapien < 400 > 114 Met Gln Cys Phe Ser Phe He Lys Thr Met Met He Leu Phe Asn Leu i 5 10 15 Leu He Phe Leu Cys GlyAla Wing Leu Leu Wing Val Gly He Trp Val 20 25 30 Being He Asp Gly Wing Being Phe Leu Lys He Phe Gly Pro Leu Ser Ser 35 40 45 Be Wing Met Gln Phe Val Asn Val Gly Tyr Phe Leu He Wing Wing Gly 50 55 60 Val Val Val Phe Wing Leu Gly Phe Leu Gly Cys Tyr Gly Wing Lys Thr 65 70 75 80 Glu Ser Lys Cys Ala LeuVal Thr Phe Phe Phe He Leu Leu Leu He 85 90 95 Phe He Wing Glu Val Wing Wing Wing Val Val Wing Leu Val Tyr Thr Thr 100 105 110 Met Wing Glu His Phe Leu Thr Leu Leu Val Val Pro Wing He Lys Lys 115 120 125 Asp Tyr Gly Ser Gln Glu Asp Phe Thr Gln Val Trp Asn Thr Thr Met 130 135 140 Lys Gly Leu Lys Cys Cys Gly Phe Thr Asn Tyr Thr Asp Phe Glu Asp 145 150 155 160 Ser Pro Tyr Phe Lys Glu Asn Ser Wing Phe Pro Pro Phe Cys Cys Asn 165 170 175. Asn Val Thr Asn Thr Wing Asn Glu Thr Cys Thr Lys Gln Lys Wing 180 185 190 His Asp Gln Lys Val Glu Gly Cys Phe Asn Gln Leu Leu Tyr Asp He 195 200 205 Arg Thr A sn Wing Val Thr Val Gly Val Val Wing Wing Gly He Gly Gly 210, "-" • "" 215 220 Leu Glu Leu Ala Wing Met He Val Ser Met Tyr Leu Tyr Cys Asn Leu 225 230 235 240 Gln
< 210 > 115 < 211 > 366 < 212 > DNA < 213 > Homo sapien < 400 > 115 gctctttctc tcccctcctc tgaatttaat tctttcaact tgcaatttgc aaggattaca 60 catttcactg tgatgtatat tgtgttgcaa aaaaaaaaaa gtgtctttgt ttaaaattac 120 ttggtttgtg aatccatctt gctttttccc cattggaact agtcattaac ccatctctga 180 actggtagaa aaacatctga agagctagtc tatcagcatc tgacaggtga attggatggt 240 tctcagaacc atttcaccca gacagcctgt ttctatcctg tttaataaat tagtttgggt 300 tttctacatg cataacaaac cctgctccaa tctgtcacat aaagtctgt gacttgaagt TTAG_360_and 366
< 210 > 116 < 211 > 282 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (282) < 223 > n = A, T, C or G < 400 > 116 acaaagatga accatttcct atattatagc aaaattaaaa tctacccgta ttctaatatt 60 gagaaatgag atnaaacaca atnttataaa gtctacttag agaagatcaa gtgacctcaa 120 agactttact attttcatat tttaagacac atgatttatc ctattttagt aacctggttc 180 atacgttaaa caaaggataa tgtgaacagc agagaggatt tgttggcaga aaatctatgt 240 actatctana tcaatctnga tcacagacat ttctattcct tt 282
< 210 > 117 < 211 > 305 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (305) < 223 > n = A, T, C or G < 400 > 117 acacatgtcg cttcactgcc ttcttagatg cttctggtca acagggacca acatanagga 60 ccctcctgaa tatttatcct acaattgcaa aataanacaa aatatatgaa acaattgcaa 120 aatatatgaa aataaggcaa acaacaggtc tcgagatatt ggaaatcagt caatgaagga 180 tactgatccc tgatcactgt cctaatgcag gatgtgggaa acagatgagg tcacctctgt 240 gactgcccca gcttactgcc tgtagagagt ttctangctg cagttcagac agggagaaat tgggt 300 305 < 210 > 118 < 211 > 71 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (71) < 223 > n = A, T, C or G < 400 > 118 accaaggtgt ntgaatctct gacgtgggga tctctgattc ccgcacaatc tgagtggaaa 60 aantcctggg t 71
< 2 10 > 119 < 211 > 212 < 2 12 > DNA < 213 > Homo s apien < 220 > < 221 > Diverse R &T R &C < 222 > (1) ... (212) < 223 > n = A, T, C or G < 400 > 119 actccggttg gtgtcagcag cacgtggcat tgaacatngc aatgtggagc ccaaaccaca 60 gaaaatgggg tgaaattggc caactttcta tnaacttatg ttggcaantt tgccaccaac 120 agtaagctgg cccttctaat aaaagaaaat tgaaaggttt ctcactaanc ggaattaant 180 aatggantca aganactccc gt aggcctcagc 212 < 210 > 120 < 211 > 90 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (90) < 223 > n = A, T, C or G < 400 > 120 actcgttgca natcaggggc cccccagagt caccgttgca ggagtccttc tggtcttgcc 60 ctccgccggc gcagaacatg ctggggtggt 90 < 210 > 121 < 211 > 218 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (218) < 223 > n = A, T, C or G < 400 > 121 tgtancgtga anacgacaga nagggttgtc aaaaatggag aanccttgaa gtcattttga 60 gaataagatt tgctaaaaga tttggggcta aaacatggtt attgggagac atttctgaag 120 atatncangt aaattangga atgaattcat ggttcttttg ggaattcctt tacgatngcc 180 agcatanact tcatgtgggg atancagcta cccttgta 218
< 210 > 122 < 211 > 17 1 < 212 > DNA < 213 > Homo sapien < 400 > 122 taggggtgta tgcaactgta aggacaaaaa ttgagactca actggcttaa ccaataaagg 60 catttgttag ctcatggaac aggaagtcgg atggtggggc atct cagtg ctgca tgagt 120 caccaccccg gcggggtcat ctgtgccaca ggtccctgtt gacagtgcgg t 171
< 210 > 123 < 2 11 > 76 < 2 12 > DNA < 2 1 3 > Homo saci in < 220 > < 221 > diverse feature < 222 > (1) ... (76) < 223 > n = A, T, C or G < 4 00 > 123 tgtagcgtga agacnacaga atggtgtgtg ctgtgctatc caggaacaca tttattatca 60 ttatcaanta ttgtgt 76 < 210 > 124 < 211 > 131 < 212 > DNA < 213 > Homo sapien < 400 > 124 acctttcccc aaggccaatg tcctgtgtgc taactggccg gctgcaggac agctgcaatt 60 caatgtgctg ggtcatatgg aggggaggag actctaaaat agccaatttt attctcttgg 120 ttaagatttg t 131 < 210 > 125 < 211 > 432 < 212 > DNA < 213 > Homo sapien < 400 > 125 ctggctatga actttatcta aatagatggt ggaaaattgc gttaccaact ataccactgg 60 cttgaaaaag aggtgatagc tcttcagagg acttgtgact tttgctcaga tgctgaagaa 120 ctacagtctg catttggcag aaatgaagat gaatttggat taaatgagga tgctgaagat 180 ttgcctcacc aaacaaaagt gaaacaactg agagaaaatt ttcaggaaaa aagacagtgg 240 ctcttgaagt atcagtcact tttgagaatg tttcttagtt actgcatact tcatggatcc 300 catggtgggg gtcttgcatc tgtaagaatg gaattgattt tgcttttgca agaatctcag 360 caggaaacat cagaaccact attttctagc cctctgtcag agcaaacctc agtgcctctc 420 ctctttgctt gt 432 < 210 > 126 < 211 > 112 < 212 > DNA < 213 > Homo sapien < 400 > 126 acacaacttg aatagtaaaa tagaaactga gctgaaattt ctaattcact ttctaaccat 60 agtaagaatg atatttcccc ccagggatca ccaaatattt ataaaaattt gt "112
< 210 > 127 < 211 > 54 < 212 > DNA < 213 > Homo sapi in < 400 > 127 accacgaaac cacaaacaag atggaagcat caatccactt gccaagcaca gcag 54
< 2 10 > 128 < 2 1 1 > 32 3 < 212 > DNA < 213 > Homo sapien < 400 > 128 acctcattag taattgtttt gttgtttcat ttttttctaa tgtctcccct ctaccagctc 60 acagaatgaa acctgagata cagccagatt aatggaagga tctctgctca tctcctttgc 120 ttctctctga agtctaggtt acccattttg gggacccatt ataggcaata aacacagttc 180 ccaaagcatt tggacagttt cttgttgtgt tttagaatgg ttttcctttt tcttagcctt 240 ttcctgcaaa aggctcactc agtcccttgc ttgctcagtg gactgggctc cccagggcct 300 323 tec aggctgcctt cttttccatg
< 210 > 129 < 211 > 192 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (192) < 223 > n = A, T, C or G < 400 > 129 acatacatgt gtgtatattt ttaaatatca cttttgtatc actctgactt tttagcatac 60 tgaaaacaca ctaacataat ttntgtgaac catgatcaga tacaacccaa atcattcatc 120 tagcacattc atctgtgata naaagatagg tgagtttcat ttccttcacg ttggccaatg 180 gataaacaaa gt 192 < 210 > 130 < 211 > 362 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (362) < 223 > n = A, T, C or G < 400 > 130 ccctttttta tggaatgagt agactgtatg tttgaanatt tanccacaac ctctttgaca 60 tataatgacg caacaaaaag gtgCtgttta gtcctatggt tcagtttatg cccctgacaa 120 gtttccattg tgttttgccg atcttctggc taatcgtggt atcctccatg ttattagtaa 180 cattttgtta ttctgtattc gatgtaacct acgcctggta taactttata gctangaggc 240 cttatttaaa agetettatt ttgtggtcat taaaatggca atttatgtgc ageaetttat 300 tgcagcagga agcacgtgtg ggttggttgt aaagctcttt getaatetta aaaagtaatg gg 360 - 362
< 210 > 131 < 211 > 332 < 212 > DNA < 213 > Homo sapien < 220 > < 22i > diverse feature < 222 > (1) ... (332) < 223 > n = A, T, C or G < 400 > 131 ctttttgaaa gatcgtgtcc actcctgtgg acatcttgtt ttaatggagt ttcccatgca 60 stan actgg tatggttgca gctgtccaga taaaaacatt tgaagagetc caaaatgaga 120 gttctcccag gttcgccctg ctgctccaag tctcagcagc agcctctttt aggaggcatc 180 ttctgaacta gattaaggca gcttgtaaat ctgatgtgat ttggtttatt atccaactaa 240 cttccatctg ttatcactgg agaaagccca gactccccan gacnggtacg gattgtgggc 300 atanaaggat tgggtgaagc gt tggcgttgtg 332
< 210 > 132 < 211 > 322 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (322) < 223 > n = A, T, C or G < 400 > 132 acttttgcca ttttgtatat ataaacaatc ttgggacatt ctcctgaaaa ctaggtgtcc 60 agtggctaag agaactcgat ttcaagcaat tctgaaagga aaaccagcat gacacagaat 120 ctcaaattcc caaacagggg ctctgtggga aaaatgaggg aggacctttg tatctcgggt 180 tttagcaagt taaaatgaan atgacaggaa aggcttattt atcaacaaag agaagagttg 240 ggatgcttct aaaaaaaact ttggtagaga aaataggaat gctnaatcct agggaagcct 300 gtaacaatct acaattggtc ca 322
< 210 > 133 < 211 > 278 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse characteristic < 222 > ( 1 ) . . . (278) < 223 > n = A, T, C or G < 400 > 133 acaagccttc acaagtttaa ctaaattggg attaatcttt ctgtanttat ctgcataatt 60 cttgtttttc tttccatctg gctcctgggt tgacaatttg tggaaacaac tctattgcta 120 aaaatcacaa ctatttaaaa atctttccct ttaagctatg ttnaattcaa actattcctg 180 ctattcctgt tttgtcaaag aaattatatt tttcaaaata tgtntatttg tttgatgggt 240 cccacgaaac actaataaaa accacagaga ccagcctg 278
< 210 > 134 < 211 > 121 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (121) < 223 > n = A, T, C or G < 400 > 134 g ttanaaaa cttgtttagc tccatagagg aaagaatgtt aaactttgta ttttaaaaca 60 tsattctctg aggttaaact tggttttcaa atgttatttt tacttgtatt ttgcttttgg 120 t "" 121
< 210 > 135 < 211 > 350 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (350) < 223 > n = A, T, C or G < 400 > 135 atgcctagca acttanaacc catcagaatc cctcaaagaa catcagtata atcctatacc 60 atancaagtg gtgactggtt aagcgtgcga caaaggtcag ctggcacattacttgtgtgc 120 aaacttgata cttttgttct aagtaggaac tagtatacag tncctaggantggtactcca 180 gggtgccccc caactcctgc agccgctcct ctgtgccagn ccctgnaaggaactttcgct 240 ccacctcaat caagccctgg gccatgctac ctgcaattgg ctgaacaaacgtttgctgag 300 ttcccaagga tgcaaagcct ggtgctcaac tcctggggcg tcaactcagt 350
< 210 > 136 < 211 > 399 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (399) < 223 > n = A, T, C or G < 400 > 136 tgtaccgtga agacgacaga agttgcatgg cagggacagg gcagggccga ggccagggtt 60 gctgtgattg tatccgaata ntcctcgtga gaaaagataa tgagatgacg tgagcagcct 120 gcagacttgt gtctgccttc aanaagccag acaggaaggc cctgcctgcc ttggctctga 180 cctggcggcc agccagccag ccacaggtgg gcttcttcct tttgtggtga caacnccaag 240 aaaactgcag aggcccaggg tcaggtgtna gtgggtangt gaccataaaa caccaggtgc 300 tcccaggaac ccgggcaaag gccatcccca cctacagcca gcatgcccac tggcgtgatg 360 ggtgcagang gatgaagcag ccagntgttc tgctgtggt 399
< 210 > 137 < 211 > 165 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (165) < 223 > n = A, T, C or G < 400 > 137 actggtgtgg tngggggtga tgctggtggt anaagttgan gtgacttcan gatggtgtgt 60 ggaggaagtg tgtgaacgta gggatgtaga ngttttggcc gtgctaaatg agcttcggga 120 ttggctggtc ccactggtgg tcactgtcat tggtggggtt cctgt 165
< 210 > 138 < 211 > 338 < 212 > DNA < 213 > Homo sapie < 220 > < 221 > diverse feature < 222 > (1) ... (338) < 223 > n = A, T, C or G < 400 > 138 actcactgga atgccacatt cacaacagaa tcagaggtct gtgaaaacat taatggctcc 60 ttaacttctc cagtaagaat cagggacttg aaatggaaac gttaacagcc acatgcccaa 120 tgctgggcag tctcccatgc cttccacagt gaaagggctt gagaaaaatc acatccaatg 180 tcatgtgttt ccagccacac caaaaggtgc ttggggtgga gggctggggg catananggt 240 gaagcctcaa cangcctcag gttccattca gctttgccac tgtacattcc ccatntttaa 300 aaaaactgat gccttttttt tttttttttg taaaattc 338
< 210 > 139 < 211 > 382 < 212 > DNA < 213 > Homo sapien < 400 > 139 gggaatcttg gtttttggca tctggtttgc ctatagccga ggccactttg acagaacaaa 60 gaaagggact tcgagtaaga aggtgattta cagccagcct agtgcccgaa gtgaaggaga 120 attcaaacag acctcgtcat tcctggtgtg agcctggtcg gctcaccgcc tatcatctgc 180 atttgcctta ctcaggtgct accggactct ggcccctgat gtctgtagtt tcacaggatg 240 ccttatttgt cttctacacc ccacagggcc ccctacttct tcggatgtgt ttttaataat 300 gtcagctatg tgccccatcc tccttcatgc cctccctccc tttcctacca ctgctgagtg 360 gcctggaact gt tgtttaaagt 382
< 210 > 140 < 211 > 200 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (200) < 223 > n = A, T, C or G < 400 > 140 accaaanctt ctttctgttg tgttngattt tactataggg gtttngcttn ttctaaanat 60 acttttcatt taacancttt tgttaagtgt caggctgcac tttgctccat anaattattg 120 ttttcacatt tcaacttgta tgtgtttgtc tcttanagca ttggtgaaat cacatatttt 180 atattcagca taaaggagaa _ 20O
< 210 > 141 < 211 > 335 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (335) < 223 > n = A, T, C or G < 400 > 141 actttatttt caaaacactc atatgttgca aaaaacacat agaaaaataa agtttggtgg 60 gggtgctgac taaacttcaa gtcacagact tttatgtgac agattggagc agggtttgtt 120 atgcatgtag agaacccaaa ctaatttatt aaacaggata gaaacaggct gtctgggtga 180 aatggttctg agaaccatcc aattcacctg tcagatgctg atanactagc tcttcagatg 240 tttttctacc agttcagaga tnggttaatg actanttcca atggggaaaa agcaagatgg 300 attcacaaac caagtaattt taaacaaaga cactt 335
< 210 > 142 < 211 > 459 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (459) < 223 > n = A, T, C or G < 400 > 142 tattgccaca accaggttaa tatatccttt ccaattgcgg gctaaacaga cgtgtattta 60 gggttgttta aagacaaccc agcttaatat caagagaaat tgtgaccttt catggagtat 120 aaacactgag ctgatggaga tcttatttta ttttgacaaa agtctgatca ttcagatagc 180 aacaacactc cacatggtcc aaataataaa tcaaatatna tcagatgtta aagattggtc 240 ttcaaacatc atagccaatg atgccccgct tgcctataat taaaaccaca ctctccgaca 300 tcaacacctc agtggccacc aaaccattca gcacagcttc cttaactgtg agctgtttga 360 agctaccagt ctgagcacta ttgactatnt ttttcangct ctgaatagct ctagggatct 420 cagcangggt gggaggaacc agctcaacct tggcgtant 459
< 210 > 143 < 211 > 140 < 212 > DNA < 213 > Homo sapien < 400 > 143 acatttcctt ccaccaagtc aggactcctg gcttctgtgg gagttcttat cacctgaggg 60 aaatccaaac agtctctcct agaaaggaat agtgtcacca accccaccca tctccctgag 120 accatccgac ttccctgtgt 140
< 210 > 144 < 211 > 164 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse character < 222 > ( 1 ) . . . (1 64) < 223 > n = A, T, C or G < 400 > 144 acttcagtaa caacatacaa taacaacatt aagtgtatat tgccatcttt gtcattttct 60 atctatacca ctctcccttc tgaaaacaan aatcactanc caatcactta tacaaatttg 120 aggcaattaa tccatatttg ttttcaataa ggaaaaaaag ATGT 164
< 210 > 145 < 211 > 303 < 2 12 > DNA < 2 13 > Homo s api in < 220 > < 221 > diverse feature < 222 > (1) ... (303) < 223 > n = A, T, C or G < 400 > 145 acgtagacca tccaactttg tatttgtaat ggcaaacatc cagnagcaat tcctaaacaa 60 actggagggt atttataccc aattatccca ttcattaaca tgccctcctc ctcaggctat 120 gcaggacagc tatcataagt cggcccaggc atccagatac taccatttgt ataaacttca 180 gtaggggagt ccatccaagt gacaggtcta atcaaaggag gaaatggaac ataagcccag 240 tagtaaaatn ttgcttagct gaaacagcca caaaagactt accgccgtgg tgattaccat 303 300 caa
< 210 > 146 < 211 > 327 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (327) < 223 > n = A, T, C or G < 400 > 146 actgcagctc aattagaagt ggtctctgac tttcatcanc ttctccctgg gctccatgac 60 actggccfcgg agtgactcat tgctctggtt ggttgagaga gctcctttgc caacaggcct 120 ccaagtcagg gctgggattt gtttcctttc cacattctag caacaatatg ctggccactt 180 cctgaacagg gagggtggga ggagccagca tggaacaagc tgccactttc taaagtagcc 240 agacttgccc ctgggcctgt cacacctact gatgaccttc tgtgcctgca ggatggaatg 300 taggggtgag ctgtgtgact ctatggt 327
< 210 > 147 < 211 > 173 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse characteristic < 222 > ( 1 ) . . . (173) < 223 > n = A, T, C or G < 400 > 147 acattgtttt tttgagataa agcattgana gagctctcct taacgtgaca caatggaagg 60 actggaacac atacccacat ctttgttctg agggataatt ttctgataaa gtcttgctgt 120 atattcaagc acatatgtta tatatt ttatagccta GTT 173 ATTC agttccatgt
< 210 > 148 < 211 > 477 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (477) < 223 > n = A, T, C or G < 400 > 148 acaaccactt tatctcatcg aatttttaac ccaaactcac tcactgtgcc tttctatcct 60 atgggatata ttatttgatg ctccatttca tcacacatat atgaataata cactcatact 120 gccctactac ctgctgcaat aatcacattc ccttcctgtc ctgaccctga agccattggg 180 gtggtcctag tggccatcag tccangcctg caccttgagc ccttgagctc cattgctcac 240 nccancccac ctcaccgacc ccatcctctt acacagctac ctccttgctc tctaacccca 300 tagattatnt ccaaattcag tcaattaagt tactattaac actctacccg acatgtccag 360 caccactggt aagccttctc cagccaacac acacacacac acacncacac acacacatat 420 f ccaggcacag gctacctcat cttcacaatc acccctttaa ttaccatgct atggtgg 477
< 210 > 149 < 211 > 207 < 212 > DNA < 213 > Homo sapien 15 < 400 > 149 acagttgtat tataatatca agaaataaac ttgcaatgag agcatttaag agggaagaac 60 taacgtattt tagagagcca aggaaggttt ctgtggggag tgggatgtaa ggtggggcct 120 gatgataaat aagagtcagc caggtaagtg ggtggtgtgg tatgggcaca gtgaagaaca 180
tttcaggcag agggaacagc agtgaaa 207 < 210 > 150 < 211 > 111 F < 212 > DNA 25 < 213 > Homo sapien < 220 > < 221 > diverse character < 222 > ( 1 ) . . . (111) 30 < 223 > n = A, T, C or G < 400 > 150 acc t tgatt t cattgctgct ctgatggaaa cccaactatc taatttagct aaaacatggg 60 cacttaaatg tggtcagtgt ttggacttgt taactantgg catctttggg t 111
< 210 > 151 < 211 > 196 < 212 > DNA < 213 > Homo sapien 40 < 400 > 151 w agcgcggcag gtcatattga acattccaga tacctatcat tactcgatgc tgttgataac '60 agcaagatgg ctttgaactc agggtcacca ccagctattg gaccttacta tgaaaaccat 120 ggataccaac cggaaaaccc ctatcccgca cagcccactg tggtccccac tgtctacgag 180
45 gtgcatccgg ctcagt '196 < 210 > 152 < 211 > 132 < 212 > DNA 50 < 213 > Homo sapien < 400 > 152 acagcacttt cacatgtaag aagggagaaa ttcctaaatg taggagaaag ataacagaac 60 cttccccttt tcatctagtg gtggaaacct gatgctttat gttgacagga atagaaccag 120
55 gagggagttt gt 132 <; 210 > 153 < 211 > 285 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (285) < 223 > n = A, T, C or G < 400 > 153 acaanaccca nganaggcca ctggccgtgg tgtcatggcc tccaaacatg aaagtgtcag 60 cttctgctct tatgtcctca tctgacaact ctttaccatt tttatcctcg ctcagcagga 120 gcacatcaat aaagtccaaa gtcttggact tggccttggc ttggaggaag tcatcaacac 180 cctggctagt gagggtgcgg cgccgctcct ggatgacggc atctgtgaag tcgtgcacca 240 gtctgcaggc cctgtggaag cgccgtccac acggagtnag gaatt 285
< 210 > 154 < 211 > 333 < 212 > DNA < 213 > Homo sapien < 400 > 154 accacagtcc tgttgggcca gggcttcatg accctttctg tgaaaagcca tattatcacc 60 accccaaatt tttccttaaa tatctttaac tgaaggggtc agcctcttga ctgcaaagac 120 cctaagccgg ttacacagct aactcccact ggccctgatt tgtgaaattg ctgctgcctg 180 attggcacag gagtcgaagg tgttcagctc ccctcctccg tggaacgaga ctctgatttg 240 attctcgggc agtttcacaa cacctcgtca ttgctcctct gaaataaaat ccggagaatg 300 gtcaggcctg tctcatccat atggatcttc cgg 333 < 210 > 155 < 211 > 308 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (308) < 223 > n = A, T, C or G < 400 > 155 ataaaaccca actggaaata catcacagtg ttgtgtcaaa gatcatcagg gcatggatgg "60 gaaagtgctt tgggaactgt aaagtgccta acacatgatc gatgattttt gttataatat 120 ttgaatcacg gtgcatacaa actctcctgc ctgctcctcc tgggccccag ccccagcccc 180 atcacagctc actgctctgt tcatccaggc ccagcatgta gtggctgatt cttcttggct 240 gcttttagcc tccanaagtt tctctgaagc caaccaaacc tctangtgta aggcatgctg 300 gccctggt 308
< 210 > 156 < 211 > 295 < 212 > DNA < 213 > Homo sapien < 400 > 156 gtgcttggaa accttgctcg actcaaaata catattagga tgagatgata acagtgccta 60 ttattgatta ctgagagaac tgttagacat ttagttgaag attttctaca caggaactga 120 gaataggaga ttatgtttgg ccctcatatt ctctcctatc ctccttgcct cattctatgt 180 ctaatatatt ctcaatcaaa taaggttagc ataatcagga aatcgaccaa ataccaatat 240 aaaaccagat gtctatcctt aagattttca aatagaaaac aaattaacag actat 295
< 210 > 157 < 211 > 126 < 212 > DNA < 213 > Homo sapien < 400 > 157 acaagtttaa atagtgctgt cactgtgcat gtgctgaaat gtgaaatcca ccacatttct 60 gaagagcaaa acaaattctg tcatgtaatc tctatcttgg gtcgtgggta tatctgtccc 120 cttagt 126
< 2 10 > 158 < 211 > 442 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (442) < 223 > n = A, T, C or G < 400 > 158 acccactggt cttggaaaca cccatcctta atacgatgat ttttctgtcg tstgaaaatg 60 aanccagcag gctgccccta gtcagtcctt ccttccagag aaaaagagat ttgagaaagt 120 ttcaccatta gcctgggtaa atttcctccc ccaaactctc tgagtcttcc cttaatattt 180 ctggtggttc tgaccaaagc aggtcatggt ttgttgagca tttgggatcc cagtgaagta 240 gccttgcata natgtttgta cttagccctt cccacgcaca aacggagtgg cagagtggtg 300 ccaaccctgt tttcccagtc cacgtagaca gattcacagt gcggaattct ggaagctgga 360 nacagacggg ctctttgcag agccgggact ctgagangga catgagggcc tctgcctctg 420 tgttcattct ctgatgtcct gt 442
< 210 > 159 < 211 > 498 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (498) < 223 > n = A, T, C or G < 400 > 159 acttccaggt aacgttgttg tttccgttga gcctgaactg atgggtgacg ttgtaggttc 60 tccaacaaga actgaggttg cagagcgggt agggaagagt gctgttccag ttgcacctgg 120 gctgctgtgg actgttgttg attcctcact acggcccaag gttgtggaac tggcanaaag 180 gtgtgttgtt gganttgagc tcgggcggct gtggtaggtt gtgggctctt caacaggggc 240 tgctgtggtg ccgggangtg aangtgttgt gtcacttgag cttggccagc tctggaaagt 30C antar.attct tcctgaaggc cagcgcttgt ggagctggca ngggtcantg ttgtgtgtaa 360 cgaaccagtg ctgctgtggg tgggtgtana tcctccacaa agcctgaagt tatggtgtcn 420 tcaggtaana atgtggtttc agtgtccctg ggcngctgtg gaaggttgta nattgtcacc 480 aagggaataa gctgtggt 498
< 210 > 160 < 211 > 380 < 212 > DNA < 213 > Homo sacien < 220 > < 221 > diverse feature < 222 > (1) ... (380) < 223 > n = A, T, C or G < 400 > 160 acctgcatcc agcttccctg ccaaactcac aaggagacat caacctctag acagggaaac 60 agcttcagga tacttccagg agacagagcc accagcagca aaacaaatat tcccatgcct 120 ggagcatggc atagaggaag ctganaaatg tggggtctga ggaagccatt tgagtctggc 180 cactagacat ctcatcagcc acttgtgtga agagatgccc catgacccca gatgcctctc 240 ccacccttac ctccatctca cacacttgag ctttccactc tgtataattc taacatcctg 300 gagaaaaatg gcagtttgac cgaacctgtt cacaacggta gaggctgatt tctaacgaaa 360 380 gaagcctgga cttgtagaat
< 210 > 161 < 211 > 114 < 212 > DNA < 213 > Homo sapien < 400 > 161 actccacatc ccctctgagc aggcggttgt cgttcaaggt gtatttggcc ttgcctgtca 60 cactgtccac tggcccctta tccacttggt gcttaatccc tcgaaagagc atgt 114 <; 210 > 162 < 211 > 177 < 212 > DNA < 213 > Homo sapien < 400 > 162 actttctgaa tcgaatcaaa tgatacttag tgtagtttta atatcctcat = tatatcaaa 60 gttttactac tctgataatt ttgtaaacca ggtaaccaga acatccar.c atacagcttt 120 tggtgatata taacttggca ataacccagt ctggtgatac ataaaactac tcactgt 177 < 210 > 163 < 211 > 137 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (137) < 223 > n = A, T, C or G < 400 > 163 cat t tataca gacaggcgtg aagacattca cgacaaaaac gcgaaatt tt atcccgtgac 60 canagaaggc agctacggct actcctacat cctggcgtgg gtggcctt tg cctgcacctt 120 catcagcggc atgatgt 137 < 210 > 164 < 211 > 4 69 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (469) < 223 > n = A, T, C or G < 400 > 164 cttatcacaa tgaatgttct cctgggcagc gttgtgatct ttgccacctt cgtgacttta 60 tgcaatgcat catgctattt catacctaat gagggagttc caggagattc aaccaggaaa 120 tcaaaggaaa tgcatggatc caaacaccca ataaactcgg agtggcagac tgacaactgt 180 gagacatgca cttgctacga aacagaaatt tcatgttgca cccttgtttc tacacctgtg 240 ggttatgaca aagacaactg ccaaagaatc ttcaagaagg aggactgcaa gtatatcgtg 300 aggacccaaa gtggagaaga aaagacctgt tctgtcagtg aatggataat ctaatgtgct 360 tctagtaggc acagggctcc caggccaggc ctcattctcc tctggcctct aatagtcaat 420 gattgtgtag ccatgcctat cagtaaaaag atntttgagc aaacacttt 469
< 210 > 165 < 211 > 195 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (195) < 223 > n = A, T, C or G < 400 > 165 acagtttttt atanatatcg acattgccgg cacttgtgtt cagtttcata aagctggtgg 60 atccgctgtc atccactatt ccttggctag agtaaaaatt attcttatag cccatgtccc 120 tgcaggccgc ccgcccgtag ttctcgttcc agtcgtcttg gcacacaggg tgccaggact 180 tcctctgaga tgagt 195 < 210 > 166 < 211 > 383 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (383) < 223 > n = A, T, C or G < 400 > 166 acatcttagt agtgtggcac atcagggggc catcagggtc acagtcactc atagcctcgc ^ 60 gtccacacca cgaggtcgga ccggtgtagg tgtgctcaat cttgggcttg gcgcccacct 120 ttggagaagg gatatgctgc acacacatgt ccacaaagcc tgtgaactcg ccaaagaatt 180 tttgcagacc agcctgagca aggggcggat gttcagcttc agctcctcct tcgtcaggtg 240 gatgccaacc tcgtctangg tccgtgggaa gctggtgtcc acntcaccta caacctgggc 300 gangatctta taaagaggct ccnagataaa ctccacgaaa cttctctggg agctgctagt 360 383 ttc nggggccttt ttggtgaact
< 210 > 167 < 211 > 247 < 212 > DNA < 213 > Homo sapien < 223 > < 22 i > diverse feature < 222 > (1) ... (247) < 223 > n = A, T, C or G < 400 > 167 acagagccag accttggcca taaatgaanc agagattaag actaaacccc aagtcganat 60 tggagcagaa actggagcaa gaagtgggcc tggggctgaa gtagagacca aggccactgc 120 tatanccata cacagagcca actctcaggc caaggcnatg gttggggcag anccagagac 180 tcaatctgan tccaaagtgg tggctggaac actggtcatg acanaggcag tgactctgac 240 tgangtc 247 < 210 > 168 < 211 > 273 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (273) < 223 > n = A, T, C or G < 400 > 168 acttctaagt tttctagaag tggaaggatt gtantcatcc tgaaaatggg tttacttcaa 60 aatccctcan ccttgttctt cacnactgtc tatactgana gtgtcatgtt tccacaaagg 120 gctgacacct gagcctgnat tttcactcat ccctgagaag ccctttccag tagggtgggc 180 caagcttccc aattcccaac ttccttgcca aggctttctc ccctggaaaa ctccagcttg 240 273 gca agtcccagat acactcatgg gctgccctgg
< 210 > 169 < 211 > 431 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (431) < 223 > n = A, T, C or G < 400 > 169 acagccttgg cttccccaaa ctccacagtc tcagtgcaga aagatcatct tccagcagtc 60 agctcagacc agggtcaaag gatgtgacat tggtttcaga caacagtttc acaggttcta 120 ctactgtcaa atgacccccc atacttcctc aaaggctgtg gtaagttttg cacaggtgag 180 ggcagcagaa agggggtant tactgatgga caccatcttc tctgtatact ccacactgac 240 cttgccatgg gcaaaggccc ctaccacaaa aacaatagga tcactgctgg gcaccagctc "300 acgcacatca ctgacaaccg ggatggaaaa agaantgcca actttcatac atccaactgg 360 aaagtgatct gatactggat tcttaattac cttcaaaagc ttctgggggc catcagctgc 420 tcgaacactg to 431
< 210 > 170 < 211 > 266 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (266) < 223 > n = A, T, C or G < 400 > 170 acctgtgggc tgggctgtta tgcctgtgcc ggctgctgaa agggagttca gaggtggagc 60 tcaaggagct ctgcaggcat tttgccaanc ctctccanag canagggagc aacctacact 120 ccccgctaga aagacaccag attggagtcc tgggaggggg agttggggtg ggcatttgat 180 gtatacttgt cacctgaatg aangagccag agaggaanga gacgaanatg anattggcct 240 gggtctggca tcaaagctag ggtgga 266
< 210 > 171 < 211 > 1248 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > characteristic liversa < 222 > (1) ... (1248) < 223 > n = A, T, C or G < 40 0 > 171 ggcagccaaa tcataaacgg cgaggactgc agcccgcact cgcagccctg gcaggcggca 60 ctggtcatgg aaaacgaatt gttctgctcg ggcgtcctgg tgcatccgca gtgggtgctg 120 tcagccgcac actgtttcca gaagtgagtg cagagctcct acaccatcgg gctgggcctg 180 cacagtcttg aggccgacca agagccaggg agccagatgg tggaggccag cctctccgta 240 cggcacccag agtacaacag acccttgctc gctaacgacc t'catgctcat caagttggac 300 gaatccgtgt ccgagtctga caccatccgg agcatcaaca ttgcttcgca gtgccctacc 360 gcggggaact cttgcctcgt ttctggctgg ggtctgctgg cgaacggcag aatgcctacc 420 gtgctgcagt gcgtgaacgt gtcggtggtg tctgaggagg tctgcagtaa gctctatgac 480 ccgctgtacc accccagcat gttctgcgcc ggcggagggc aagaccagaa ggactcctgc 540 aacggtgact ctggggggcc cctgatctgc aacgggtact tgcagggcct tgtgtctttc 600 ggaaaagccc cgtgtggcca agttggcgtg ccaggtgtct acaccaacct ctgcaaattc 660 actgagtgga tagagaaaac cgtccaggcc agttaactct ggggactggg aacccatgaa 720 attgaccccc aaatacatcc tgcggaagga attcaggaat atctgttccc agcccctcct 780 caggagtcca ccctcaggcc ggcccccagc ccctcctccc tcaaaccaag ggtacagatc 840 cccagcccct cctccctcag acccaggagt ccagaccccc cagcccctcc tccctcagac 900 ccaggagtcc agcccctcct ccctcagacc caggagtcca gaccccccag cccctcctcc 960 ctcagaccca ggggtccagg cccccaaccc ctcctccctc agactcagag gtccaagccc 1020 attccccaga ccaacccntc cccagaggtc caggtcccag cccctcntcc ctcagaccca 1080 gcggtccaat gccacctaga ctntccctgt acacagtgcc cccttgtggc acgttgaccc 1140 aaccttacca gttggttttt catttttngt ccctttcccc tagatccaga caaaaaaaaa aaaaaaaaaa aataaagttt 1200 aaaaaaaaaa aaaaaaaa aagagaagng 1248
< 210 > 172 < 211 > 159 < 212 > PRT < 213 > Homo sapien < 220 > < 221 > VARIANT < 222 > (1) ... (159) < 223 > Xaa = Any amino acid < 400 > 172 Met Val Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro 1 5 10 15 Leu Leu Aia. Asn Leu Met Leu He Lys Leu Asp Glu Ser Val Ser 20 25 30 Glu Ser Asp Thr He Arg Ser He Ser He Wing Being Gln Cys Pro Tnr 35"43 45 Wing Gly Asr. Ser Cys Leu Val Being Gly Trp Gly Leu Leu Wing Asn C-Iy 50 55 60 Arg Met Pro Thr Val Leu Gln Cys Val Asn Val Ser Val Val Ser Glu 65 70 75 80 Glu Val Cys Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Ser Met Phe 85 90 95 Cys Wing Gly Gly Gly Gln Xaa Gln Xaa Asp Ser Cys Asn Gly Asp Ser 100 105 110 Gly Gly Pro Leu He Cys Asn Gly Tyr Leu Gln Gly Leu Val Ser Phe 115 120 125 Gly Lys Wing Pro Cys Gly Gln Val Gly Val Pro Gly Val Tyr Thr Asn 130 135 140 Leu Cys Lys Phe Thr Glu Trp He Glu Lys Thr Val Gln Wing Ser 145 150 155 <210 > 173 <211> 1265 <212> DNA <213> Homo sapien <220> <221> miscellaneous feature <222> (1). (1265) < 223 > n = A, T, C, or G < 400 > 173 ggcagcccgc actcgcagcc ctggcaggcg gcactggtca tggaaaacga attgttctgc 60 tcgggcgtcc tggtgcatcc gcagtgggtg ctgtcagccg cacactgttt ccagaactcc 120 tacaccatcg ggctgggcct gcacagtctt gaggccgacc aagagccagg gagccagatg 180 gtggaggcca gcctctccgt gagtacaaca acggcaccca gacccttgct cgctaacgac 240 tcaagttgga ctcatgctca cgaatccgtg tccgagtctg acaccatccg gagcatcagc 300 attgcttcgc agtgccctac cgcggggaac tcttgcctcg rttctggctg gggtctgctg 360 gcgaacggtg agctcacggg tgtgtgtctg ccctcttcaa ggaggtcctc tgcccagtcg 420 cgggggctga cccagagctc tgcgtcccag gcagaatgcc taccgtgctg cagtgcgtga 480 acgtgtcggt ggtgtctgag gaggtctgca gtaagctcta tgacccgctg taccacccca 540 gcatgttctg cgccggcgga gggcaagacc agaaggactc ctgcaacggt gactctgggg 600 ggcccctgat ctgcaacggg tacttgcagg gccttgtgtc tttcggaaaa gccccgtgtg 660 gccaagttgg cgtgccaggt gtctacacca acctctgcaa attcactgag tggatagaga 720 ggccagttaa aaaccgtcca ctctggggac tgggaaccca tgaaattgac ccccaaatac 780 atcctgcgga aggaattcag gaatatctgt tcccagcccc tcctccctca ggcccaggag 840 tccaggcccc cagccc CTCC tccctcaaac caagggtaca gatccccagc ccctcctccc 900 tcagacccag gagtccagac cccccagccc ctcctccctc agacccagga gtccagcccc 960 tcctccntca gacccaggag tccagacccc ccagcccctc ctccctcaga cccaggggtt 1020 gaggccccca acccctcctc cttcagagtc agaggtccaa gcccccaacc cctcgttccc 1080 cagacccaga ggtnnaggtc ccagcccctc ttccntcaga cccagnggtc caatgccacc 1140 tagattttcc ctgnacacag tgcccccttg tggnangttg acccaacctt accagttggt 1200 ttttcatttt tngtcccttt cccctagatc cagaaataaa ngngcaaaaa gtttaagaga _ 1260 aaaaa 1265
< 210 > 174 < 211 > 1459 < 212 > DNA < 213 > Homo sapien < 220 > < 22 1 > Characteristically t i ca dive rsa < 222 > ( 1 ) . . . (1459) < 223 > n = A, T, C or G < 4 00 > 174 gg _ - = accyc CCAEC gt ttc cagaagtgag tgcagagctc ctacaccatc gggctgggcc 60 tgcacagtct tgaggccgac caagagccag ggagccagat ggtggaggcc agcctctccg 120 tacggcaccc agagtacaac agacccttgc tcgctaacga cctcatgctc atcaagttgg 180 acgaatccgt gtccgagtct gacaccatcc ggagcatcag cattgcttcg cagtgcccta 240 ccgcggggaa ctcttgcctc gtttctggct ggggtctgct ggcgaacggt gagctcacgg 300 gtgtgtgtct gccctcttca aggaggtcct ctgcccagtc gcgggggctg acccagagct 360 ctgcgtccca ggcagaatgc ctaccgtgct gcagtgcgtg aacgtgtcgg tggtgtctga 420 ngaggtctgc antaagctct atgacccgct gtaccacccc ancatgttct gcgccggcgg 480 agggcaagac cagaaggact cctgcaacgt gagagagggg aaaggggagg gcaggcgact 540 cagggaaggg tggagaaggg ggagacagag acacacaggg ccgcatggcg agatgcagag 600 atggagagac acacagggag acagtgacaa ctagagagag aaactgagag aaacagagaa 660 ataaacacag gaataaagag aagcaaagga agagagaaac agaaacagac atggggaggc 720 acacatagaa agaaacacac atgcagttga ccttccaaca gcatggggcc tgagggcggt 780 caatagaaaa gacctccacc tcctcttata acttttgact ccccaaaaac ctgactagaa 840 atagcctact gttgacgggg agccttacca ataacataaa tagtcgattt atgcatacgt 900 tttatgcatt catgatatac ctttgttgga attttttgat atttctaagc tacacagttc 960 gtctgtgaat ttttttaaat tgttgcaact ctcctaaaat ttttctgatg tgtttattga 1020 aaaaatccaa gtataagtgg acttgtgcat tcaaaccagg gttgttcaaq ggtcaactgt 1080 gtacccagag ggaaacagtg acacagattc atagaggtga gaaacaggaa aacacgaaga 1140 aaatcaagac tctacaaaga ggctgggcag ggtggctcat gcctgtaatc ccagcacttt 1200 gggaggcgag gcaggcagat cacttgaggt aaggagttca agaccagcct ggccaaaatg 1260 gtctgtacta gtgaaatcct aaaatacaaa agttagctgg atatggtggc aggcgcctgt 1320 aatcccagct acttgggagg ctgaggcagg agaattgctt gaatatggga ggcagaggtt 1380 gaagtgagtt gagatcacac cactatactc cagctggggc aacagagtaa gactctgtct 1440 caaaaaaaaa aaaaaaaaa 1459
< 210 > 175 < 211 > 1167 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (1167) < 223 > n = A, T, C or G < 400 > 175 gcscagccct ggcaggcggc actggtcatg gaaaacgaat tgttctgctc gggcgtcctg 60 gt catccgc agtgggtgct gtcagccgca cactgtttcc agaactccta caccatcggg 120 acagtcttga ctgggcctgc gagccaggga ggccgaccaa gccagatggt ggaggccagc 180 ctctccgtac ggcacccaga gtacaacaga ctcttgctcg ctaacgacct catgctcatc 240 aagttggacg aatccgtgtc cgagtctgac accatccgga gcatcagcat tgcttcgcag 300 tgccctaccg cggggaactc ttgcctcgtn tctggctggg gtctgctggc gaacggcaga 360 atgcctaccg tgctgcactg cgtgaacgtg tcggtggtgt ctgaggangt ctgcagtaag 420 ctctatgacc cgctgtacca ccccagcatg ttctgcgccg gcggagggca agaccagaag "480 gactcctgca acggtgactc tggggggccc ctgatctgca acgggtactt gcagggcctt 540 gtgtctttcg gaaaagcccc gtgtggccaa cttggcgtgc caggtgtcta caccaacctc 600 tgcaaattca ctgagtggat agagaaaacc gtccagncca gttaactctg gggactggga 660 ttgaccccca acccatgaaa gcggaangaa aatacatcct tctgttccca ttcaggaata 720 gcccctcctc cctcaggccc aggagtccag gcccccagcc cctcctccct caaaccaagg 780 gtacagatcc ccagcccctc ctccctcaga cccaggagtc cagacccccc agcccctcnt 840 ccntcagacc cagg agtcca gcccctcctc cntcagacgc aggagtccag accccccagc 900 ccntcntccg tcagacccag gggtgcaggc ccccaacccc tcntccntca gagtcagagg 960 tccaagcccc caacccctcg ttccccagac ccagaggtnc aggtcccagc ccctcctccc 1020 tcagacccag cggtccaatg ccacctagan tntccctgta ccttgtggca cacagtgccc 1080 ngttgaccca accttaccag ttggtttttc attttttgtc cctttcccct agatccagaa 1140 1167 ataaagtnta agagaagcgc aaaaaaa
< 210 > 176 < 211 > 205 < 212 > PRT < 213 > Homo sapien < 220 > < 221 > VARIANT < 222 > (1) ... (205) < 223 > Xaa = Any amino acid < 400 > 176 Met Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gln Trp 1 5 10 15 Val Leu Ser Ala Ala His Cys Phe Gln Asn Ser Tyr Thr He Gly Leu 20 25 30 Gly Leu His Ser Leu Glu Wing Asp Gln Glu Pro Gly Ser Gln Met Val 35 40 45 Glu Wing Ser Leu Ser Val. Arg His Pro Glu Tyr Asn Arg Leu Leu Leu 50 55 60 Wing Asn Asp Leu Met Leu He Lys Leu Asp Glu Ser Val Ser Glu Ser 65 70 75 80 Asp Thr He Arg Be He Be Wing Be Wing Gln Cys Pro Thr Wing Gly 85 90 95 Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Wing Asn Gly Arg Met 100 105 110 Pro Thr Val Leu His Cys Val Asn Val Ser Val Val Ser Glu Xaa Val 115 120 125 Cys Ser Lys Leu Tyr .Asp Pro Leu Tyr His Pro Ser Met Phe Cys Ala 130 135 140 Gly Gly Gly Gln .Asp Gln Lys Asp Ser Cys Asn Gly Asp Ser Gly Gly 145 150 155 160 Pro Leu He Cys Asn Gly Tyr Leu Gln Gly Leu Val Ser Phe Gly Lys 165 170 175 Wing Pro Cys Gly Gln Leu Gly Val Pro Gly Val Tyr Thr Asn Leu Cys 180 185 190 Lys Phe Thr Glu Trp He Glu Lys Thr Val Gln Xaa Ser 195 200 205 < 210 > 177 < 211 > 1119 < 212 > DNA < 213 > Homo sapien < 400 > 177 gcgcactcgc agccctggca ggcggcactg gtcatggaaa acgaattgtt ctgctcgggc 60 gtcctggtgc atccgcagtg ggtgctgtca gccgcacact gtttccagaa ctcctacacc 120 atcgggctgg gcctgcacag tcttgaggcc gaccaagagc cagggagcca gatggtggag. 180 gccagcctct ccgtacggca cccagagtac aacagaccct tgctcgctaa cgacctcatg 240 ctcatcaagt tggacgaatc cgtgtccgag tctgacacca tccggagcat cagcattgct 300 tcgcagtgcc ctaccgcggg gaactcttgc ctcgtttctg gctggggtct gctggcgaac 360 ttgccatcca gatgctgtga gtcccagact gtgggaggct gggagtgtga gaagctttcc 420 caaccctggc agggttgtac catttcggca acttccagtg caaggacgtc ctgctgcatc 480 ctcactgggt gctcactact gctcactgca tcacccggaa cactgtgatc aactagccag 540 caccatagtt ctccgaagtc agactatcat gattactgtg ttgactgtgc tgtctattgt 600 actaaccatg ccgatgttta ggtgaaatta gcgtcacttg gcctcaacca tcttggtatc 660 cagttatcct cactgaattg agatttcctg cttcagtgtc agccattccc acataatttc 720 tgacctacag aggtgaggga tcatatagct cttcaaggat gctggtactc ccctcacaaa 780 ttcatttctc ctgttgtagt gaaaggtgcg ccctctggag cctcccaggg tgggtgtgca 840 ggtcacaatg atgaatgtat gatcgtgttc ccattaccca aagcctttaa atccctcatg 900 ctcagtacac cagggcaggt ctagcatttc ttcatttagt gtatgctgtc cattcatgca 960 accacctcag gactcctgcra ttctctgcct agttgagctc ctgcatgctg cctccttggg 1020 gaggtgaggg aga gggccca tggttcaatg ggatctgtgc agttgtaaca cattaggtgc 1080 ttaa.aaaca gaa.'ttcrtca tgttaaaaaa aaaaaaaaa 1119 <; 210 > 178 < 211 > 164 < 212 > PRT < 213 > Homo sapien < 220 > < 221 > VARIANT < 222 > (1) ... (164) < 223 > Xaa = Any amino acid < 400 > 178 Met Glu Asn Glu Leu Phe Lys Ser Gly Val Leu Val His Pro Gln Trp 1 5 10 15 Val Leu Ser Wing Wing His Cys Phe Gln Asn Ser Tyr Thr He Gly Leu 20 25 30 Gly Leu His Ser Leu Glu Wing Asp Gln Glu Pro Gly Ser Gln Met Val 35 40 45 Glu Wing Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro Leu Leu 50 55 60 Wing Asn Asp Leu Met Leu He Lys Leu Asp Glu Ser Val Ser Glu Ser 65 70 75 80 Asp Thr He Arg Being He Be Wing Being Gln Cys Pro Thr Wing Gly 85 90 95 Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Wing Asn Asp A. Val 100 105 110 He Wing He Gln Ser Xaa Thr Val Gly Gly Trp Glu Cys Glu Lvs Leu 115 120 125 Ser Gln Pro Trp Gln Gly Cys Thr He Ser Wing Thr Ser Se r Wing Arg 130 135 140 Thr Ser Cys Cys He Leu Thr Gly Cys Ser Leu Leu Leu Thr Ala Se r 145 150 155 160 Pro Gly Thr Leu
< 210 > 179 < 211 > 250 < 212 > DNA < 213 > Homo sapien < 400 > 179 ctggagtgcc ttggtgtttc aagcccctgc aggaagcaga atgcaccttc tgaggcacct 60 ccagctgccc ccggccgggg gatgcgaggc tcggagcacc cttgcccggc tgtgattgct 120 gccaggcact gttcatctca gcttttctgt ccctttgctc ccggcaagcg cttctgctga 180 aagttcatat ctggagcctg atgtcttaac gaataaaggt cccatgctcc acccgaaaaa aaaaaaaaaa 240 250
< 210 > 180 < 211 > 202 < 212 > DNA < 213 > Homo sapien < 400 > 180 actagtccag tgtggtggaa ttccattgtg ttgggcccaa cacaatggct acctttaaca 60 tcacccagac cccgcccctg cccgtgcccc acgctgctgc taacgacagt atgatgctta 120 ctctgctact cggaaactat ttttatgtaa ttaatgtatg ctttcttgtt tataaatgcc 180 tgatttaaaa aaaaaaaaaa aa 202
< 210 > 181 < 211 > 558 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (558) < 223 > n = A, T, C or G < 400 > 181 tccytttgkt naggtttkkg agacamccck agacctwaan ctgtgtcaca gacttcyngg 60 aatgtttagg cagtgctagt aatttcytcg taatgattct gttattactt tcctnattct 120 ttcttctgaa ttattcctct gattaatgaa gttgaaaatt gaggtggata aatacaaaaa 180 ggtagtgtga tagtataagt atctaagtgc agatgaaagt tatccattca gtgttatata 240 aaattatgca agttagtaat tactcagggt taactaaatt actttaatat gctgttgaac 300 ctactctgtt ccttggctag aaaaaattat aaacaggact ttgttagttt gggaagccaa 360 attgataata ttctatgttc taaaagttgg gctatacata aattattaag aaatatgga 420 ttttattccc aggaatatgg kgttcatttt atgaatatta cscrggatag awgtwtgagt 480 aaaaycagtt ttggtwaata ygtwaatatg tcmtaaataa acaakgctut gacttatttc 540 caaaaaaaaa aaaaaaaa 558
< 210 > 182 < 211 > 479 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (479) < 223 > n = A, T, C or G < 400 > 182 grggatgcta acagggwttk agsccccrga r tygtttga tccaaccctg gctt ttttc 60 agaggggaaa atggggccta gaagttacag scatytagy tggtgcgmtg gcacccctgg 120 cstcacacag astcccgagt agctgggact acaggcacac agtcactgaa gcaggccctg 180 ttwgcaattc acgttgccac ctccaactta aacattcttc atatgtgatg tccttagtca 240 ctaaggttaa actttcccac ccagaaaagg caacttagat aaaatcttag agtactttca 300 tact ttcta agtcctcttc cagcctcact kkgagtcctm cytgggggtt gataggaant 360 ntctcttggc tttctcaata aartctctat ycatctcatg tttaatttgg tacgcatara 420 awtgstgara aaattaaaat gttctggtty actttaaaa araaaaaaaa aaaaaaaaa 479
< 210 > 183 < 211 > 384 < 212 > DNA < 213 > Homo sapien < 400 > 183 aggcgggagc agaagctaaa gccaaagccc aagaagagtg gcagtgccag cactggtgcc 60 agtaccagta ccaataacag tgccagtgcc agtgccagca ccagtggtgg cttcagtgct 120 ggtgccagcc tgaccgccac tctcacattt gggctcttcg ctggccttgg tggagctggt 180 gccagcacca gtggcagctc tggtgcctgt ggtttctcct acaagtgaga ttttagatat 240 tgttaatcct gccagtcttt ctcttcaagc cagggtgcat cctcagaaac ctactcaaca 300 cagcactcta ggcagccact atcaatcaat tgaagttgac actctgcatt aratctattt 360 aaaaaaaaaa aaaa 384 gccatttcaa
< 210 > 184 < 211 > 496 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (496) < 223 > n = A, T, C or G < 400 > 184 accgaattgg gaccgctggc ttataagcga tcatgtyynt ccrgtatkac ctcaacgagc 60 agggagatcg agtctatacg ctgaagaaat ttgacccgat gggacaacag acctgctcag 120 cccatcctgc tcggttctcc ccagatgaca aatactctsg acaccgaatc accatcaaga 180 aacgcttcaa ggtgctcatg acccagcaac cgcgccctgt cctctgaggg tcccttaaac 240 tgatgtcttt tctgccacct gttacccctc ggagactccg taaccaaact cttcggactg 300 tgagccctga tgcctttttg ccagccatac tctttggcat ccagtctctc gtggcgattg 360 attatgcttg tgtgaggcaa tcatggtggc atcacccata aagggaacac atttgacttt 420 tttttctcat attttaaatt actacmaga tattwmagaw waaatga tt gaaaaactst 480 taaaaaaaaaaaaaaa 496
< 210 > 185 < 211 > 384 < 212 > DNA < 213 > Homo sapien < 400 > 185 gctggtagcc tatggcgkgg cccacggagg ggctcctgag gccacggrac agtgacttcc 60 caagtatcyt gcgcsgcgtc ttctaccgtc cctacctgca gatcttcggg cagattcccc 120 aggaggacat ggacgtggcc ctcatggagc acagcaactg ytcgtcggag cccggcttct 180 gggcacaccc tcctggggcc caggcgggca cctgcgtctc ccagtatgcc aactggctgg 240 tggtgctgct cctcgtcatc ttcctgctcg tggccaacat cctgctggtc aacttgctca 300 cagttacaca ttgccatgtt ttcggcaaag tacagggcaa cagcgatctc tactgggaag gcgcagcgtt accgcctcat GGCC 360 384
< 210 > 186 < 211 > 577 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (577) < 223 > n = A, T, C or G < 40 0 > 186 gagttagctc ctccacaacc ttgatgaggt cgtctgcagt ggcctctcgc ttcataccgc 60 tnccatcgtc atactgtagg tttgccacca cytcctggca tcttggggcg gcntaatatt 120 ccaggaaact ctcaatcaag tcaccgtcga tgaaacctgt gggctggttc tgtcttccgc 180 tcggtgtgaa aggatctccc agaaggagtg ctcgatcttc cccacacttt tgatgacttt 240 attgagtcga ttctgcatgt ccagcaggag gttgtaccag ctctctgaca gtgaggtcac 300 TATC atgccgttga mcgtgccgaa garcaccgag ccttgtgtgg gggkkgaagt 360 ttctgcatta ctcacccaga ccagagagcc gtggcaaaag acattgacaa actcgcccag 420 gtggaaaaag amcamctcct ggargtgctn gccgctcctc gtcmgttggt ggcagcgctw 480 tccttttgac acacaaacaa gttaaaggca ttttcagccc ccagaaantt gtcatcatcc 540 aagatntcgc acagcactna tccagttggg attaaat 577
< 210 > 187 < 211 > 534 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (534) < 223 > n = A, T, C or G < 400 > 187 aacatcttcc tgtataatgc tgtgtaatat cgatccgatn ttgtctgstg agaatycatw 60 gmaacattaa actkggaaaa agcctggaca ctggtattaa aattcacaat atgcaacact 120 ttaaacagtg tgtcaatctg ctcccyynac tttgtcatca ccagtctggg aakaagggta 180 tgccctattc acacctgtta aaagggcgct aagcattttt gattcaacat cttttttttt 240 gacacaagtc cgaaaaaagc aaaagtaaac agttatyaat ttgttagcca attcactttc 300 ttcatgggac agagccatyt gatttaaaaa gcaaattgca taatattgag cttygggagc 360 gcggaagagt tgatatttga cttcaccaga agcctttcta cacaactccc tttcatattg 420 ggatgttnac naaagtwatg tctctwacag atgggatgct tttgtggcaa ttctgttctg 480 aggatctccc agtttattta ccacttgcac aagaaggcgt tttcttcctc aggc 534
< 210 > 188 < 211 > 761 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (761) < 223 > n = A, T, C or G < 400 > 188 agaaaccagt atctctnaaa acaacctctc ataccttgtg gacctaattt tgtgtgcgtg 60 tgtgtgtgcg cgcatattat atagacaggc acatcttttt tacttttgta aaagcttatg 120 cctctttggt atctatatct gtgaaagttt taatgatctg ccataatgtc ttggggacct 180 ttgtcttctg tgtaaatggt actagagaaa acacctatnt tatgagtcaa tctagttngt 240 atgaaggaaa tttattcgac tttccagatn acaacactna caaactctcc ctkgackarg 300 aaaagcaaaa ggggacaaag ctgamcataa raaacaatwa cctggtgaga arttgcataa 360 acagaaatwr ggtagtatat tgaarnacag catcattaaa rmgttwtktt wttctccctt 420 gcaaaaaaca tgtacngact tcccgttgag taatgccaag ttgttttttt tatnataaaa 480 cttgcccttc attacatgtt tnaaagtggt gtggtgggcc aaaatattga aatgatggaa 540 ctgactgata aagctgtaca gtgcctaaca aataagcagt agcaacacag taatgttgac 600 atgcttaatt cacaaatgct aatttcatta taaatgtttg ctaaaataca ctttgaacta 660 tttttctgtn ttcccagagc tgagatntta gattttatgt agtatnaagt gaaaaantac 720 acattgaaga gaaaataata aaaananaaa aaanaaaaaa 761
< 210 > 189 < 211 > 482 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (482) < 223 > n = A, T, C or G < 400 > 189 tttttttttt tttgccgatn ctactatttt attgcaggan gtgggggtgt atgcaccgca 60 caccggggct atnagaagca agaaggaagg agggagggca cagccccttg ctgagcaaca 120
: G ctgccttctc tgtctgtctc ctqgtgcagg cacatgggga gaccttcccc 180 aaggcagggg ccaccagtcc aggggtggga atacaggggg tgggangtgr gcataagaag 240 tgataggcac aggccacccg gtacagaccc ctcggctzct gacaggtnga tttcgaccag 300 gtcattgtgc cctgcccagg cacagcgtan atctggaaaa gacagaatgc tttccetttc 360 aaatttggct ngtcatngaa ngggcanttt tccaanttng gctnggtctt ggtacncttg 420 gttcggccca gctccncgtc caaaaantat tcacccnnct ccnaattgct tgcnggnccc 480 482 ce
< 210 > 190 < 211 > 471 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (471) < 223 > n = A, T, C or G < 400 > 190 ttttaaaaca tttttttttt acaaaattta gtttttcaca ttagaagaat agtggttttg 60 aaaactctcg catccagtga gaactaccat acaccacatt atgtnctcca acagctngga 120 aatgtctggt caaatgatac aatggaacca ttcaatctta cacatgcacg aaagaacaag 180 cgcttttgac atacaatgca caaaaaaaaa aggggggggg gaccacatgg attaaaattt 240 taagtactca tcacatacat taagacacag ttctagtcca gtcnaaaatc agaactgcnt 300 tgaaaaattt catgtatgca atccaaccaa agaacttnat tggtgatcat gantnctcta 360 ctacatcnac cttgatcatt gccaggaacn aaaagttnaa ancacncngt acaaaaanaa 420 tctgtaattn anttcaacct ccgtacngaa aaatnttnnt tatacactcc c 471
< 210 > 191 < 211 > 402 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (402) < 223 > n = A, T, C or G < 400 > 191 gagggattga aggtctgttc tastgtcggm ctgttcagcc accaactcta acaagttgct 60 gtcttccact cactgtctgt aagcttttta acccagacwg tatcttcata aatagaacaa 120 attcttcacc agtcacatct tctaggacct ttttggattc agctcttcca agttagtata 180 cttcctttgt taagacttca tctggtaaag tcttaagttt tgtagaaagg aattyaattg _ 240 ctcgttctct aacaatgtcc tctccttgaa gtatttggct gaacaaccca cctaaagtcc 300 ctttgtgcat ccattttaaa tatacttaat agggcattgk tncactaggt taaattctgc 360 aagagtcatc tgtctgcaaa agttgcgtta gtatatctgc ca 402
< 210 > 192 < 211 > 601 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (601) < 223 > n = A, T, C or G < 400 > 192 gagctcggat ccaataatct ttgtctgagg gcagcacaca tatncagtgc catggnaact 60 ggtctacccc acatgggagc agcatgccgt agntatataa ggtcattccc tgagtcagac 120 atgcytyttt gaytaccgtg tgccaagtgc tggtgattct yaacacacyt ccatcccgyt 180 cttttgtgga aaaactggca cttktctgga actagcarga catcacttac aaattcaccc 240 acgagacact tgaaaggtgt aacaaagcga ytcttgcatt gctttttgtc cctccggcac 300 cagttgtcaa tactaacccg ctggtttgcc tccatcacat ttgtgatctg tagctctgga 360 tacatctcct gacagtactg aagaacttct tcttttgttt caaaagcarc tcttggtgcc 420 tgttggatca ggttcccatt tcccagtcyg aatgttcaca tggcatattt wacttcccac 480 aaaacattgc gatttgaggc tcagcaacag caaatcctgt tccggcattg gctgcaagag 540 cctcgatgta gccggccagc gccaaggcag gcgccgtgag ccccaccagc agcagaagca 600 g 601
< 210 > 193 < 211 > 608 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (608) < 223 > n = A, T, C or G < 400 > 193 atacagccca natcccacca cgaagatgcg cttgttgact gagaacctga tgcggtcact 60 ggtcccgctg tagccccagc gactctccac ctgctggaag cggttgatgc tgcactcytt 120 cccaacgcag gcagmagcgg gsccggtcaa tgaactccay tcgtggcttg gggtkgacgg 180 tkaagtgcag gaagaggctg accacctcgc ggtccaccag gatgcccgac tgtgcgggac 240 ctgcagcgaa actcctcgat ggtcatgagc gggaagcgaa tgaggcccag ggccttgccc 300 agaaccttcc gcctgttctc tggcgtcacc tgcagctgct gccgctgaca ctcggcctcg 360 gaccagcgga caaacggcrt tgaacagccg cacctcacgg atgcccagtg tgtcgcgctc 420 caggammgsc accagcgtgt ccaggtcaat gtcggtgaag ccctccgcgg gtratggcgt 480 ctgcagtgtt tttgtcgatg ttctccaggc acaggctggc cagctgcggt tcatcgaaga 540 gtcgcgcctg cgtgagcagc atgaaggcgt tgtcggctcg cagttcttct tcaggaactc 600 cacgcaat 608
< 210 > 194 < 211 > 392 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (392) < 223 > n = A, T, C or G < 400 > 194 gaacggctgg accttgcctc gcattgtgct tgctggcagg gaataccttg gcaagcagyt 60 ccagtccgag cagccccaga ccgctgccgc ccgaagctaa gcctgcctct ggccttcccc 120 tgcagaacca tccgcctcaa gtagtgggag cactgtgttt agagttaaga gtgaacactg 180 tttgatttta cttgggaatt tcctctgtta tatagctttt cccaatgcta atttccaaac 240 aacaacaaca aaataacatg tttgcctgtt aagttgtata aaagtagatg attctgtatt 300 taaagaaaat attactgtta catatactgc ttgcaatttc tgtatttatt gktnctstgg 360 aaataaatat agttattaaa ggttgtcant ce 392 < 210 > 195 < 211 > 502 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (502) < 223 > n = A, T, C or G < 400 > 195 ccsttkgagg ggtkaggkyc cagttyccga gtggaagaaa caggccagga gaagtgcgtg 60 ccgagctgag gcagatgttc ccacagtgac ccccagagcc stgggstata gtytctgacc 120 cctcncaagg aaagaccacs ttctggggac atgggctgga gggcaggacc tagaggcacc 180 aagggaaggc cccattccgg ggstgttccc cgaggaggaa gggaaggggc tctgtgtgcc 240 ccccasgagg aagaggccct gagtcctggg atcagacacc ccttcacgtg tatccccaca 300 caaatgcaag ctcaccaagg tcccctctca gtccccttcc stacaccctg amcggccact 360 gscscacacc cacccagagc acgccacccg ccatggggar tgtgctcaag gartcgcngg 420 gcarcgtgga catctngtcc cagaaggggg cagaatctcc aatagangga ctgarcmstt 480 gctnanaaaa aaaaanaaaa aa 502
< 210 > 196 < 211 > 665 < 212 > DNA < 213 > Homo sapien < 220 > < 221 >; diverse feature < 222 > (1) ... (665) < 223 > n = A, T, C or G < 400 > 196 ggttacttgg tttcattgcc accacttagt ggatgtcatt tagaaccatt ttgtctgctc 60 cctctggaag ccttgcgcag agcggacttt gtaattgttg gagaataact gctgaatttt 120 wagctgtttk gagttgatts gcaccactgc acccacaact tcaatatgaa aacyawttga 180 actwatttat tatcttgtga aaagtataac aatgaaaatt ttgttcatac tgtattkatc 240 aagtatgatg aaaagcaawa gatatatatt cttttattat gttaaattat gattgccatt 300 attaatcggc aaaatgtgga gtgtatgttc ttttcacagt aatatatgcc ttttgtaact 360 tcacttggtt attttattgt aaatgartta caaaattctt aatttaagar aatggtatgt 420 watatttatt tcattaattt ctttcctkgt ttacgtwaat tttgaaaaga wtgcatgatt 480 tcttgacaga aatcgatctt gatgctgtgg aagtagtttg acccacatcc ctatgagttt 540 ttcttagaat gtataaaggt tgtagcccat cnaacttcaa agaaaaaaat gaccacatac 600 tttgcaatca ggctgaaatg tggcatgctn ttctaattcc aactttataa actagcaaan aagtg 660 665
< 210 > 197 < 211 > 492 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (492) < 223 > n = A, T, C or G < 400 > 197 ttttnttttt ttttttttgc aggaaggatt ccatttattg tggatgcart ttcacaatat 60 atgtttattg gagcgatcca aaagtatcaa ttatcagtga gtgtttataa natttttagg 120 aaggcagatt cacagaacat gctngtcngc ttgcagtttt acctcgtana gatnacagag 180 aattatagtc naaccagtaa acnaggaatt tacttttcaa aagattaaat ccaaactgaa 240 caaaattcta ccctgaaact tactccatcc aaatattgga ataanagtca gcagtgatac 300 attctcttct gaactttaga aaatatgtaa ttttctagaa tagtgatcag gaagagctct 360 tgttcaaaag tacaacnaag caatgttccc ttaccatagg ccttaattca aactttgatc 420 catttcactc ccatcacggg agtcaatgct acctgggaca cttgtatttt gttcatnctg 480 ancntggctt aa 492 < 210 > 198 < 211 > 478 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (478) < 223 > n = A, T, C or G < 400 > 198 tttnttttgn atttcantct gtannaanta ttttcattat gtttattana aaaatatnaa 60 tgtntccacn acaaatcatn ttacntnagt aagaggccan ctacattgta caacatacac 120 ttgaaaagga tgagtatatt caagtttaaa gtanacncat attgccganc atancacatt 180 tatacatggc ttgattgata tttagcacag canaaactga gtgagttacc agaaanaaat 240 aatcngattt natatatgtc aagatacaaa acagatccta tggtacatan catcntgtag 300 gagttgtggc tttatgttta ctgaaagtca atgcagttcc gatggccgta tgtacaaaga 360 agcattctag tacctctact ccatggttaa gaatcgtaca catatgtnca cttatgttta 420 gggtaagaat tgtgttaagt naanttatgg agaggtccan gagaaaaatt tgatncaa 478 < 210 > 199 < 211 > 482 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (482) < 223 > n = A, T, C or G < 400 > 199 cctccaacaa agtgacttgt tcaagtttgt aaccccttga atcagaccta ggcactgaca 60 tgctagttcc tgtcatctat tcgctactaa atgcagactg aaaaggggca gaggggacca 120 tcaactccag ctggattatt ttggagcctg caaatctatt cggactttga cctacttgta 180 agtgattcag tttcctctac ggatgagaga ctggctcaag tgcagcttta aatatcctca 240 tgaagccnac tctgaacacg ctggttatct nagatgagaa ncagagaaat aaagtcnaga 300 aaatttacct ggangaaaag aggctttngg ctggggacca tcccattgaa ccttctctta 360 anggacttta agaanaaact accacatgtn tgtngtatcc tggtgccngg ccgtttantg - 420 aacntngacn ncacccttnt ggaatanant cttgacngcn tcctgaactt gctcctctgc 480 g 482
< 210 > 200 < 211 > 270 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (270) < 223 > n = A, T, C or G < 400 > 200 tgcaactcca cggccgcaag gctggggccg tgcggacgaa gattctgcca gcagttggtc 60 cgactgcgac gacggcggcg gcgacagtcg ggggtcttgc 120 caggtgcagc gcgggcgcct tgacgccgca aaggctgagc gaggtcgtgt cacgtcccac gaccttgacg ccgtcgggga 180 cagccggaac agagcccggt gaangcggga ggcctcgggg agcccctcgg gaagggcggc 240 cgcaggtgca ccgagagata ggtggccgcc 270
< 210 > 201 < 211 > 419 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (419) < 223 > n = A, T, C or G < 400 > 201 tttttttttt ttttggaatc tactgcgagc acagcaggtc agcaacaagt ttattttgca 60 gctagcaagg taacagggta gggcatggtt acatgttcag gtcaacttcc tttgtcgtgg 120 ttgattggtt tgtctttatg ggggcggggt ggggtagggg aaancgaagc anaantaaca 180 tggagtgggt gcaccctccc tgtagaacct ggttacnaaa gcttggggca gttcacctgg 240 tctgtgaccg tcattttctt gacatcaatg ttattagaag tcaggatatc ttttagagag 300 tccactgtnt ctggagggag attagggttt cttgccaana atccacntga tccaancaaa 360 aaaagttgga tgatncangt acngaatacc ganggcatan ttctcatant cggtggcca 419
< 210 > 202 < 211 > 509 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (509) < 223 > n = A, T, C or G < 400 > 202 tttntttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60 tggcacttaa tccattttta tttcaaaatg tctacaaant ttnaatncnc cattatacng 120 aaaatctaaa gtnattttnc atntnagcca nnttattcaa ncaaatnnaa aantccttac 180 tacncncaaa aatcaaaaat atacntntct ttcagcaaac ttngttacat aaattaaaaa 240 aatatatacg gctggtgttt tcaaagtaca attatcttaa atntttnnaa cactgcaaac 300 taaaaaaaaa ggaactaaaa aaggttaaag cactnccgca ggaacaacaa attcntttta 360 nattataaaa caacancnnc atcatatctc aaatcttagg ggaatatata cttcacacng _ 420 ggatcttaac ttttactnca ctttgtttat ttttttanaa ccattgtntt gggcccaaca 480 caatggnaat nccnccncnc tggactagt 509
< 210 > 203 < 211 > 583 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (583) < 223 > n = A, T, C or G < 400 > 203 tttttttttt ttttttttga cccccctctt ataaaaaaca agttaccatt ttattttac tacacatatt tattttataa ttggtattag atattcaaaa ggcagctttt aaaatcaaac 120 ctgccttaga taaatggaaa tacataattc ttaggaatta gcttaaaatc tgcctaaagt 180 gaaaatcttc tctagctctt ttgactgtaa atttttgact cttgtaaaac atccaaattc 240 atttttcttg tctttaaaat tatctaatct ttccattttt tccctattcc aagtcaattt 300 gcttctctag cctcatttcc tagctcttat ctactattag taagtggctt ttttcctaaa 360 ggaagagana agggaaaaca atggcacaca aaacaaacat tttatattca tatttctacc 420 tacgttaata aaatagcatt ttgtgaagcc agctcaaaag aaggcttaga tccttttatg 480 tccattttag tcactaaacg atatcnaaag tgccagaatg caaaaggttt gtgaacattt 540 attcaaaagc taatataaga tatttcacat actcatcttt ctg 583
< 210 > 204 < 211 > 589 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (589) < 223 > n = A, T, C or G < 400 > 204 ttttttttnt tttttttttt ttttttnctc ttcttttttt ttganaatga ggatcgagtt 60 tttcactctc tagatagggc atgaagaaaa ctcatctttc ataacaatca cagctttaaa 120 aatctcttat gctatatcat attttaagtt aaactaatga gtcactggct tatcttctcc 180 tgaaggaaat ctgttcattc ttctcattca tatagttata tcaagtacta ccttgcatat 240 ttcttctcta tgagaggttt tttacacata tatttccatg tgaatttgta tcaaaccttt 300 aaactagaaa attttcatgc ataatgtntt cttttgcata agagaagaga acaatatnag 360 cattacaaaa ctgctcaaat tgtttgttaa gnttatccat tataattagt tnggcaggag 420 ctaatacaaa tcacatttac ngacnagcaa taataaaact gaagtaccag ttaaatatcc 480 aaaataatta aaggaacatt ttatagcctgg gtataattag ctaattcact ttacaagcat 540 ttattnagaa tgaattcaca tgttattatt ccntagccca acacaatgg 589
< 210 > 205 < 211 > 545 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (545) < 223 > n = A, T, C or G < 400 > 205 tttttntttt ttttttcagt aataatcaga acaatattta tttttatatt taaaattcat 60 agaaaagtgc cttacattta ataaaagttt gtttctcaaa gtgatcagag gaattagata 120 caccaatatt tngtcttgaa aatttgagga aaatacacca aaatacatta agtaaattat 180 ttaagatcat agagcttgta taaaatttga agtgaaaaga cctcagaaac tctgagcatt 240 aaaaatccac tattagcaaa taaattacta tggacttctt gctttaattt tgtgatgaat 300 atggggtgtc actggtaaac caacacattc tgaaggatac atracttagt gatagattct 360 tatgtacttt gctanatnac gtggatatga gttgacaagt ttctctttct tcaatctttt 420 aaggggcnga ngaaatgagg aagaaaagaa aaggattacg catactgttc tttctatngg 480 aaggattaga tatgtttcct ttgccaatat taaaaaaata ataatgttta ctactagtga 540 aaccc 545 < 210 > 206 < 211 > 487 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (487) < 223 > n = A, T, C or G < 400 > 206 tttttttttt ttttttagtc aagtttctna tttttattat aattaaagtc ttggtcattt 60 catttattag ctctgcaact tacatattta aattaaagaa acgttnttag acaactgtna 120 caatttataa atgtaaggtg ccattattga gtanatatat tcctccaaga gtggatgtgt 180 cccttctccc accaactaat gaancagcaa cattagttta attttattag tagatnatac 240 actgctgcaa acgctaattc tcttctccat ccccatgtng atattgtgta tatgtgtgag 300 tgcatcanca ttggtnagaa atctnacaat caacagcaag atgaagctag gcntgggctt 360 tcggtgaaaa tagactgtgt ctgtctgaat caaatgatct gacctatcct cggtggcaag 420 aactcttcga accgcttcct caaaggcngc tgccacattt gtggcntctn ttgcacttgt 480 ttcaaaa 487
< 210 > 207 < 211 > 332 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (332) < 223 > n = A, T, C or G < 400 > 207 tgaattggct aaaagactgc atttttanaa ctagcaactc ttatttcttt cctttaaaaa 60 tacatagcat taaatcccaa atcctattta aagacctgac agcttgagaa ggtcactact 120 gcatttatag gaccttctgg tggttctgct gttacntttg atccttgana aantctgaca 180 atctttgcat gcagaggagg taaaaggtat cagaggaana tggattttca acacagcgca 240 gaaatgaagg ggccaggctt actgagcttg tccactggag ggctcatggg tgggacatgg 300 aaaagaaggc agcctaggcc ctggggagcc ca 332
< 210 > 208 < 211 > 524 < 212 > DNA < 213 > Homo sapien <; 220 > < 221 > diverse feature < 222 > (1) ... (524) < 223 > n = A, T, C or G < 400 > 208 agggcgtggt gcggagggcg ttactgtttt gtctcagtaa caataaatac aaaaagactg 60 gttgtgttcc ggccccatcc aaccacgaag ttgatttctc ttgtgtgcag agtgactgat 120 tttaaaggac atggagcttg tcacaatgtc acaatgtcac agtgtgaagg gcacactcac 180 tcccgcgtga ttcacattta gcaaccaaca atagctcatg agtccatact tgtaaatact 240 tacttnttga tttggcagaa aacttgcaga tgataactaa gatccaagat atttcccaaa 300 gtaaatagaa gtgggtcata atattaatta tcagcttcca cctgttcaca tttacaagtc 360 atgagcccag acactgacat caaactaagc ccacttagac tcctcaccac cagtctgtcc 420 tgtcatcaga caggaggctg tcaccttgac caaattctca ccagtcaatc atcta ccaa 480 aaaccattac ctgatccact tccggtaatg caccaccttg gtga 524 < 210 > 209 < 211 > 159 < 212 > DNA < 213 > Homo sapien < 400 > 209 gggtgaggaa atccagagtt gccatggaga aaattccagt gtcagcattc ttgctccttg 60 tggccctctc ctacactctg gccagagata ccacagtcaa acctggagcc aaaaaggaca 120 caaaggactc tcgacccaaa ctgccccaga ccctctcca 159> 210 < 211 > 256 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (256) < 223 > n = A, T, C or G < 400 > 210 actccctggc agacaaaggc agaggagaga gctctgttag ttctgtgttg ttgaactgcc 60 actgaatttc tttccacttg gactattaca gggactaatg tgccanttga gaaaaacgta 120 tggggagatt ttanccaatt tangtntgta aatggggaga ctggggcagg cgggagagat 180 ttgcagggtg naaatgggan ggctggtttg ttanatgaac agggacatag gaggtaggca 240 256 aaatca ccaggatgct
< 210 > 211 < 211 > 264 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (264) < 223 > n = A, T, C or G < 400 > 211 tttgagataa acattgtttt agcattgaga gagctctcct taacgtgaca caatggaagg 60 actggaacac atacccacat ctttgttctg agggataatt ttctgataaa gtcttgctgt 120 atattcaagc acatatgtta tatattattc agttccatgt ttatagccta gttaaggaga 180 ggggagatac attcngaaag aggactgaaa agtnggaaaa gaaatactca cagaaaaaga 240 aaaaaaggag caaatgagaa STAG_264_< 210 > 212 < 211 > 328 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (328) < 223 > n = A, T, C or G < 400 > 212 acccaaaaat ccaatgctga atatttggct tcattattcc canattcttt gattgtcaaa 60 ggatttaatg ttgtctcagc ttgggcactt cagttaggac ctaaggatgc cagccggcag 120 gtttatatat gcagcaacaa tattcaagcg cgacaacagg ttattgaact tgcccgccag 180 ttnaatttca ttcccattga cttgggatcc ttatcatcag ccagagagat tgaaaattta 240 cccctacnac tctttactct ctgganaggg ccagtggtgg tagctataag cttggccaca 300 tttttttttc ctttattcct ttgtcaga 328 < 210 > 213 < 211 > 250 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > 15 different feature < 222 > (1) ... (250) < 223 > n = A, T, C or G < 400 > 213 acttatgagc agagcgacat atccnagtgt agactgaata aaactgaatt ctctccagtt 60
taaagcattg ctcactgaag ggatagaagt gactgccagg agggaaagta agccaaggct 120 cattatgcca aagganatat acatttcaat tctccaaact tcttcctcat tccaagagtt 180 ttcaatattt gcatgaacct gctgataanc catgttaana aacaaatatc tctctnacct 240 tctcatcggt 250 f 25 < 210 > 214 < 211 > 444 < 212 > DNA < 213 > Homo sapien 30 < 220 > < 221 > diverse feature < 222 > (1) ... (444) < 223 > n = A, T, C or G < 400 > 214 acccagaatc caatgctgaa tatttggctt cattattccc agattctttg attgtcaaag 60 gatttaatgt tgtctcagct tgggcacttc agttaggacc taaggatgcc agccggcagg 120 tttatatatg cagcaacaat attcaagcgc gacaacaggt tattgaactt gcccgccagt 180 tgaatttcat tcccattgac ttgggatcct tatcatcagc canagagatt gaaaatttac 240
40 ccctacgact ctttactctc tggagagggc cagtggtggt agctataagc ttggccacat 300 f ttttttttcc tttattcctt tgtcagagat gcgattcatc catatgctan aaaccaacag 360 agtgactttt acaaaattcc tataganatt gtgaataaaa ccttacctat agttgccatt 420 actttgctct ccctaatata cctc 444
45 < 210 > 215 < 211 > 366 < 212 > DNA < 213 > Homo sapien 50 < 220 > < 221 > diverse feature < 222 > (1) ... (366) < 223 > n = A, T, C or G 33 < 400 > 215 gagc agagcgacat atccaagtgt anactgaata aaattgaatt ctctccagtt. 60: .- JJJC tcactgaag ggatagaagt gactgccagg ag raaagta agccaaggct 120 cattatgcca aagganatat acatttcaat tctccaaact tcttcctcat tccaagagtt 180 ttcaatattt gcatgaacct gctgataagc catgttgaga aacaaatatc tctctgacct 240 tctcatcggt aagcagaggc tgtaggcaac atggaccata gcgaanaaaa aacttagtaa 300 tccaagctgt tttctacact gtaaccaggt ttccaaccaa ggtggaaatc tcctatactt ggtgcc 360 366
< 210 > 216 < 211 > 260 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (260) < 223 > n = A, T, C or G < 400 > 216 ctgtataaac agaactccac tgcangaggg agggccgggc caggagaatc tccgcttgtc 60 caagacaggg gcctaaggag ggtctccaca ctgctnntaa gggctnttnc atttttttat 120 taataaaaag tnnaaaaggc ctcttctcaa cttttttccc ttnggctgga aaatttaaaa 180 atcaaaaatt tcctnaagtt ntcaagctat catatatact ntatcctgaa aaagcaacat 240 aattcttcct tccctccttt 260 < 210 > 217 < 211 > 262 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (262) < 223 > n = A, T, C or G < 400 > 217 acctacgtgg gtaagtttan aaatgttata atttcaggaa naggaacgca tataattgta 60 tcttgcctat aattttctat tttaataagg aaatagcaaa ttggggtggg gggaatgtag 120 ggcattctac agtttgagca aaatgcaatt aaatgtggaa ggacagcact gaaaaatttt 180 atgaataatc tgtatgatta tatgtctcta gagtagattt ataattagcc acttacccta 240 262 tgcttgtaaa gt atatccttca
< 210 > 218 < 211 > 205 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (205) < 223 > n = A, T, C or G < 400 > 218 accaaggtgg tgcattaccg gaantggatc aangacacca tcgtggccaa cccctgagca 60 cccctatcaa ctcccttttg tagtaaactt ggaaccttgg aaatgaccag gccaagactc 120 aggcctcccc agttctactg acctttgtcc ttangtntna ngtccagggt tgctaggaaa 180 anaaatcagc agacacaggt gtaaa 205 < 210 > 219 < 211 > 114 < 212 > DNA < 213 > Homo sapien < 400 > 219 tactgttttg tctcagtaac aataaataca aaaagactgg ttgtgttccg gccccatcca 60 accacgaagt tgatttctct tgtgtgcaga gtgactgatt ttaaaggaca tgga 114
< 210 > 220 < 211 > 93 < 212 > DNA < 213 > Homo sapien < 400 > 220 actagccagc acaaaaggca gggtagcctg aattgctttc tgctctttac atttctttta 60 aaataagcat ttagtgctca gtccctactg agt 93 < 210 > 221 < 211 > 167 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (167) < 223 > n = A, T, C or G < 400 > 221 actangtgca ggtgcgcaca aatatttgtc gatattccct tcatcttgga ttccatgagg 60 tcttttgccc agcctgtggc tctactgtag taagtttctg ctgatgagga gccagnatgc 120 cccccactac cttccctgac gctccccana aatcacccaa cctctgt 167 < 210 > 222 < 211 > 351 < 212 > DNA < 213 > Homo sapien < 400 > 222 agggcgtggt gcggagggcg gtactgacct cattagtagg aggatgcatt ctggcacccc 60 gttcttcacc tgtcccccaa tccttaaaag gccatactgc ataaagtcaa caacagataa 120 aattaaagga atgtttgctg tggatgaaaa aaattaataa tgaatttttg cataatccaa 180 ttttctcttt tatatttcta gaagaagttt ctttgagcct attagatccc gggaatcttt 240 tgattagaga taggtgagca gcttgtaggt tgcttttaca tatatctggc atatttgagt 300 ctcgtatcaa aacaatagat tggtaaaggt ggtattattg tattgataag t 351
< 210 > 223 < 211 > 383 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (383) < 223 > n = A, T, C or G < 40 0 > 223 aacaaaaaaa aaaacaaaca attcagaaaa acaattcttc attatcttag ggactgatat 60 tggtaattat ggtcaattta atwrtrttkt ggggcatttc cttacattgt cttgacaaga 120 tgtgccaaaa ttaaaatgtc ttttgtattt tatttggaga cttcttatca aaagtaatgc 180 tgccaaagga agtctaagga attagtagtg ttcccmtcac ttgtttggag tgtgctattc 240 taaaagattt tgatttcctg gaatgacaat tatattttaa ctttggtggg ggaaanagtt 300 ataggaccac agtcttcact tctgatactt gtaaattaat cttttattgc acttgttttg 360 383 aaa tatatgttta accattaagc
< 210 > 224 < 211 > 320 < 212 > DNA < 213 > Homo sapien < 400 > 224 cttcttgtta cccctgaagg gaaaatagta cagttacaac caataggaac aacaaaaaga 60 aaaagtttgt gacattgtag tagggagtgt gtacccctta ctccccatca aaaaaaaaat 120 ggatacatgg ttaaaggata raagggcaat attttatcat atgttctaaa agagaaggaa 180 gagaaaatac tactttctcr aaatggaagc ccttaaaggt gctttgatac tgaaggacac 240 aaatgtggcc gtccatcctc ctttaragtt gcatgacttg gacacggtaa ctgttgcagt 300 tttaractcm gcattgtgac 320 < 210 > 225 < 211 > 1214 < 212 > DNA < 213 > Homo sapien < 40 0 > 225 gaggactgca gcccgcactc gcagccctgg caggcggcac tggtcatgga aaacgaattg 60 ttctgctcgg gcgtcctggt gcatccgcag tgggtgctgt cagccgcaca ctgtttccag 120 aactcctaca ccatcgggct gggcctgcac agtcttgagg ccgaccaaga gccagggagc 180 cagatggtgg aggccagcct ctccgtacgg cacccagagt acaacagacc cttgctcgct 240 tgctcatcaa aacgacctca gttggacgaa tccgtgtccg agtctgacac catccggagc 300 atcagcattg cttcgcagtg ccctaccgcg gggaactctt gcctcgtttc tggctggggt 360 ctgctggcga acggcagaat gcctaccgtg ctgcagtgcg tgaacgtgtc ggtggtgtct 420 gaggaggtct gcagtaagct ctatgacccg ctgtaccacc ccagcatgtt ctgcgccggc 480 ggagggcaag accagaagga ctcctgcaac ggtgactctg gggggcccct gatctgcaac 540 gggtacttgc agggccttgt gtctttcgga aaagccccgt gtggccaagt tggcgtgcca 600 ggtgtctaca ccaacctctg caaattcact gagtggatag agaaaaccgt ccaggccagt 660 taactctggg gactgggaac ccatgaaatt gacccccaaa tacatcctgc ggaaggaatt 720 caggaatatc tgttcccagc ccctcctccc tcaggcccag gagtccaggc ccccagcccc 780 tcctccctca aaccaagggt acagatcccc agcccctcct ccctcagacc caggagtcca 840 gaccccccag cccctc CTCC ctcagaccca ggagtccagc ccctcctccc tcagacccag 900 gagtccagac cccccagccc ctcctccctc agacccaggg gtccaggccc ccaacccctc 960 ctcagaggtc ctccctcaga caagccccca acccctcctt ccccagaccc agaggtccag 1020 gtcccagccc ctcctccctc agacccagcg gtccaatgcc acctagactc tccctgtaca 1080 cagtgccccc ttgtggcacg ttgacccaac cttaccagtt ggtttttcat tttttgtccc tttcccctag 1140 aaaaaaaaaa aaaaaaaaaa atccagaaat aaagtctaag agaagcgcaa aaaaaaaaaa aaaa 1200 1214
< 210 > 226 < 211 > 119 < 212 > DNA < 213 > Homo sapien < 400 > 226 acccagtatg tgcagggaga cggaacccca tgtgacagcc cactccacca gg? 60 agaacctggc ccagtcataa tcattcatcc tgacagtggc aataatcacg ataaccagt 119
< 210 > 227 < 211 > 818 < 212 > DNA < 213 > Homo sapien < 400 > 227 gggacgacca acaattcata atgaggacag ggaatgaacc cggctctccc ccagccctga 60 tttttgctac atatggggtc ccttttcatt ctttgcaaaa acactgggtt ttctgagaac 120 acggacggtt cttagcacaa tttgtgaaat ctgtgtaraa ccgggctttg caggggagat 180 ctctggagga aattttcctc ttgacaggca aaggtggtga gacaaggcta gggagacagt 240 gagaaagcca cgctcggcct tctctgaacc aggatggaac ggcagacccc tgaaaacgaa 300 gcttgtcccc ttccaatcag ccacttctga gaacccccat ctaacttcct actggaaaag 360 agggcctcct caggagcagt ccaagagttt tcaaagataa cgtgacaact accatctaga 420 ggaaagggtg caccctcagc agagaagccg agagcttaac tctggtcgtt tccagagaca 480 acctgctggc tgtcttggga tgcgcccagc ctttgagagg ccactacccc atgaacttct 540 gccatccact ggacatgaag ctgaggacac tgggcttcaa cactgagttg tcatgagagg 600 gacaggctct gccctcaagc cggctgaggg cagcaaccac tctcctcccc tttctcacgc 660 aaagccattc ccacaaatcc agaccatacc atgaagcaac gagacccaaa cagtttggct 720 caagaggata tgaggactgt ctcagcctgg ctttgggctg acaccatgca cacacacaag 780 gtccacttct aggttttcag cctagatggg agtcgtgt 818
< 210 > 228 < 211 > 744 < 212 > DNA < 213 > Homo sapien < 400 > 228 actggagaca ctgttgaact tgatcaagac ccagaccacc ccaggtctcc ttcgtgggat 60 gtcatgacgt ttgacatacc tttggaacga gcctcctcct tggaagatgg aagaccgtgt 120 tcgtggccga cctggcctct cctggcctgt ttcttaagat gcggagtcac atttcaatgg 180 taggaaaagt ggcttcgtaa aatagaagag cagtcactgt ggaactacca aatggcgaga 240 tgctcggtgc acattggggt gctttgggat aaaagattta tgagccaact attctctggc 300 accagattct aggccagttt gttccactga agcttttccc acagcagtcc acctctgcag 360 gctggcagct gaatggcttg ccggtggctc tgtggcaaga tcacactgag atcgatgggt 420 gagaaggcta ggatgcttgt ctagtgttct tagctgtcac gttggctcct tccaggttgg 480 ccagacggtg ttggccactc ccttctaaaa cacaggcgcc ctcctggtga cagtgacccg 540 ccgtggtatg ccttggccca ttccagcagt cccagttatg catttcaagt ttggggtttg 600 ttcttttcgt taatgttcct ctgtgttgtc agctgtcttc atttcctggg ctaagcagca 660 ttgggagatg tggaccagag atccactcct taagaaccag tggcgaaaga cactttcttt cttcactctg aagtagctgg TGGT 720 744
< 210 > 229 < 211 > 300 < 212 > DNA < 213 > Homo sapien < 400 > 229 cgagtctggg ttttgtctat aaagtttgat ccctcctttt ctcatccaaa tcatgtgaac 60 cattacacat cgaaataaaa gaaaggtggc agacttgccc aacgccaggc tgacatgtgc 120 tgcagggttg ttgtttttta attattattg ttagaaacgt cacccacagt ccctgttaat 180 ttgtatgtga cagccaactc tgagaaggtc ctatttttcc acctgcagag gatccagtct 240 cactaggctc ctccttgccc tcacactgga gtctccgcca gtgtgggtgc ccactgacat 300
< 210 > 230 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 230 aatacaaata cagcagaaca tgaagagtgc aaagatctca taaaatctat gctgaggaat 60 tcaaggagga gagcgacagt gaagcttgca gagcagctca agcaagctga ggagctcagg 120 tcctggttca caatataaag cactcaggaa cgagagctga cccagttaag ggagaagttg 180 cgggaaggga gagatgcctc cctctcattg aatgagcatc tccaggccct cctcactccg 240 acaagtccca gatgaaccgg ggggcaggac ctccaagaaa cagacctcgg ccgcgaccac 300 g 301
< 210 > 231 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 231 gcaagcacgc tggcaaatct ctgtcaggtc agctccagag aagccattag tcattttagc 60 caggaactcc aagtccacat ccttggcaac tggggacttg cgcaggttag ccttgaggat 120 ggcaacacgg gacttctcat caggaagtgg gatgtagatg agctgatcaa gacggccagg 180 tctgaggatg gcaggatcaa tgatgtcagg ccggttggta ccgccaatga tgaacacatt 240 tttttttgtg gacatgccat ccatttctgt caggatctgg ttgatgactc ggtcagcagc 300 c 301
< 210 > 232 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 232 agtaggtatt tcgtgagaag ttcaacacca aaactggaac atagttctcc ttcaagtgtt 60 ggcgacagcg gggcttcctg attctggaat ataactttgt gtaaattaac agccacctat 120 agaagagtcc atctgctgtg aaggagagac agagaactct gggttccgtc gtcctgtcca 180 cgtgctgtac caagtgctgg tgccagcctg ttacctgttc tcactgaaaa tctggctaat 240 gctctrgtgt atcacttctg attctgacaa tcaatcaatc aatggcctag agcactgact 300 g 301
< 210 > 233 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 233 atgactgact tcccagtaag gctctctaag gggtaagtag gaggatccac aggatttgag 60 atgctaaggc cccagagatc gtttgatcca accctcttat tttcagaggg gaaaatgggg 120 cctagaagtt acagagcatc tagctggtgc gctggcaccc ctggcctcac acagactccc 180 gagtagctgg gactacaggc acacagtcac tgaagcaggc cctgttagca attctatgcg 240 catgagatga tacaaattaa gtagagactt tattgagaaa gcaagagaaa atcctatcaa 300 c 301
< 210 > 234 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 234 agrtcctaca catcgagact catcoatgat tgatatgaat ttaaaaatta caagcaaaga 60 cattttattc atcatgatgc tttcttttgt ttcttctttt cgttttcttc tttttctttt 120 tcaatttcag caacatactt ctcaalttct tcaggattta aaatcttgag ggattgatct 180 cgcctcatga cagcaagttc aatgtttttg ccacctgact gaaccacttc caggagtgcc 240 ttgatcacca gcttaatggt cagatcatct gcttcaatgg cttcgtcagt atagttcttc 300 t 301
< 210 > 235 < 211 > 283 < 212 > DNA < 213 > Homo sapien < 400 > 235 tggggctgtg catcaggcgg gtttgagaaa tattcaattc tcagcagaag ccagaatttg 60 aattccctca tcttttaggg aatcatttac caggtttgga gaggattcag acagctcagg 120 tgctttcact aatgtctctg aacttctgtc cctctttgtt catggatagt ccaataaata 180 atgttatctt tgaactgatg ctcataggag agaatataag aactctgagt gatatcaaca 240 ttagggattc aaagaaatat tagatttaag tea ctcacactgg 283
< 210 > 236 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 236 aggtcctcca ccaactgcct gaagcacggt taaaattggg aagaagtata gtgeageata 60 aatactttta aatcgatcag atttccctaa atettettea cccacatgca ccagaagagg 120 atcattaata tcggagcagc ecaageagaa tgcgtaatag ataaatacaa tggtatatag 180 tgggtagacg gcttcatgag tacagtgtac tgtggtatcg taatctggac ttgggttgta 240 aagcatcgtg taccagtcag aaageatcaa tactegacat gaaegaatat aaagaacacc 300-301
< 210 > 237 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 237 cagtggtagt ggtggtggac gtggcgttgg tcgtggtgcc ttttttggtg cccgtcacaa 60 actcaatttt tgttcgctcc tttttggcct tttccaattt gtccatctca attttctggg 120 ccttggctaa tgcctcatag taggagtcct cagaccagcc atggggatca aacatatcct 180 ttgggtagtt ggtgccaagc tcgtcaatgg cacagaatgg ateagettet cgtaaatcta 240 attctttctt gggttccgaa cctttggata atgtagttca tatccattcc ctcctttatc 300 t 301
< 210 > 238 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 238 tttttttttt gggcaggttt ttttttgatg gtgcagaccc ttgctttatt tgtctgactt 60 gttcacagtt cagccccctg ctcagaaaac caacgggcca ggaggaggca gctaaggaga 120 ccttgagact tccggagtcg aggctctcca gggttcccca gcccatcaat cattttctgc 180 accccctgcc tgggaagcag ctccctgggg ggtgggaatg agggatttca ggtgactaga 240 gtgtgggacc cagggtctgt tetteacagt aggaggtgga agggatgact aatttcttta 300 t 301
< 210 > 239 < 211 > 239 < 212 > DNA < 213 > Homo sapien < 400 > 239 ataagcagct agggaattct ttatttagta atgtcctaac ataaaagttc acataactgc 60 ttctgtcaaa ccatgatact gagctttgtg acaacccaga aataactaag agaaggcaaa 120 cataatacct tagagatcaa gaaacattta cacagttcaa ctgtttaaaa atagctcaac 180 attcagccag tgagtagagt gtgaatgcca gcatacacag tatacaggtc cttcaggga 239
< 210 > 240 < 211 > 300 < 212 > DNA < 213 > Homo sapien < 400 > 240 ggtcctaatg aagcagcagc ttccacattt taacgcaggt ttacggtgat actgtccttt 60 gggatctgcc ctccagtgga accttttaag gaagaagtgg gcccaagcta agttccacat 120 gctgggtgag ccagatgact tctgttccct ggtcactttc ttcaatgggg cgaatggggg 180 ctgccaggtt tttaaaatca tgcttcatct tgaagcacac ggtcacttca ccctcctcac 240 gctgtgggtg tactttgatg aaaataccca ctttgttggc ctttctgaag ctataatgtc 300
< 210 > 241 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 241 gaggtctggt gctgaggtct ctgggctagg aagaggagtt ctgtggagct ggaagccaga 60 ggaaactcca cctctttgga gcagctatgt tggtgtctct gagggaatgc aacaaggctg 120 ctcctccatg tattggaaaa ctgcaaactg gactcaactg gaaggaagtg ctgctgccag 180 tgtgaagaac cagcctgagg tgacagaaac ggaagcaaac aggaacagcc agtcttttct 240 tcctcctcct gtcatacggt ctctctcaag catcctttgt tgtcaggggc ctaaaaggga 300 g 301
< 210 > 242 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 242 ccgaggtcct gggatgcaac caatcactct gtttcacgtg acttttatca ccatacaatt 60 tgtggcattt cctcattttc tacattgtag aatcaagagt gtaaataaat gtatatcgat 120 gtcttcaaga atatatcatt cctttttcac tagaacccat tcaaaatata agtcaagaat 180 cttaatatca acaaatatat caagcaaact ggaaggcaga ataactacca taatttagta 240 aagttttata taagtaccca aatcaaaagc accattttta cctaatgata gaattcaatc 300-301
< 210 > 243 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 243 aggtaagtcc cagtttgaag ctcaaaagat ctggtatgag cataggctca tcgacgacat 60 ggtggcccaa gctatgaaat cagagggagg cttcatctgg gcctgtaaaa actatgatgg 120 tgacgtgcag tcggactctg tggcccaagg gtatggctct ctcggcatga tgaccagcgt 180 gctggtttgt ccagatggca agacagtaga agcagaggct gcccacggga ctgtaacccg 240 atgttccaga tcactaccgc aaggacagga gacgtccacc aatcccattg cttccatttt 300 t 301 < 210 > 244 < 211 > 300 < 212 > DNA < 213 > Homo sapien < 400 > 244 gctggtttgc aagaatgaaa tgaatgattc tacagctagg acttaacctt gaaatggaaa 60 gtcatgcaat cccatttgca ggatctgtct gtgcacatgc ctctgtagag agcagcattc 120 ccagggacct tggaaacagt tgacactgta aggtgcttgc tccccaagac acatcctaaa 180 aggtgttgta atggtgaaaa cgtcttcctt ctttattgcc ccttcttatt tatgtgaaca 240 actgtttgtc ttttgtgtat cttttttaaa ctgtaaagtt caattgtgaa aatgaatatc 300
< 210 > 245 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 245 gtctgagtat ttaaaatgtt attgaaatta tccccaacca atgttagaaa agaaagaggt 60 tatatactta gataaaaaat gaggtgaatt actatccatt gaaatcatgc tcttagaatt 120 gatattgtca aaggccagga cttcaggaca ttaatgtara ctagagtata gcagccctat 180 gttttcaaag agcagagatg ttgtttagca caattaaata tcaaaaaggc cactcaatac 240 agctaataaa atgaaagacc taatttctaa agcaattctt tataatttac aaagttttaa 300 g 301
< 210 > 246 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 246 ggtctgtcct acaatgcctg gaagtcggca cttcttgaaa tagctaaata ctttctagaa 60 attttaaaga acctgggctt actatttgta gctcagattg gttttcctat ggctaaaata 120 agtgcttctt gtgaaaatta aataaaacag ttaattcaaa gccttgatat atgttaccac 180 taacaatcat actaaatata ttttgaagta caaagtttga catgctctaa agtgacaacc 240 ttacaaaaca caaatgtgtc cgttcctaac aaggtatgct ttacactacc aatgcagaaa 300 c 301 < 210 > 247 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 247 aggtcctttg gcagggctca tggatcagag ctcaaactgg agggaaaggc atttcgggta 60 gcctaagagg gcgactggcg gcagcacaac caaggaaggc aaggttgttt cccccacgct 120 gtgtcctgtg ttcaggtgcg acacacaatc ctcatgggaa caggatcacc catgcgctgc 180 ccttgatgat caaggttggg gcttaagtgg attaagggag gcaagttctg ggttccttgc 240 cttttcaaac catgaagtca ggctctgtat ccctcctttt cctaactgat attctaacta 300-301
< 210 > 248 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 248 aggtccttgg agatgccatt tcagccgaag gactcttctw ttcggaagta caccctcact 60 attaggaaga ttcttagggg taatttttct gaggaaggag aactagccaa cttaagaatt 120 agtggtttgg acaggaagaa aagacagcca aagaaataaa agcagattaa attgtatcag 180 gtacattcca gcctgttggc aactccataa aaacatttca gattttaatc ccgaatttag 240 ctaatgagac tggatttttg ttttttatgt tgtgtgtcgc agagctaaaa actcagttcc 300 c 301
< 210 > 249 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 249 gtccagagga agcacctggt gctgaactag gcttgccctg ctgtgaactt gcacttggag 60 ccctgacgct gctgttctcc ccgaaaaacc cgaccgacct ccgcgatctc cgtcccgccc 120 ccagggagac acagcagtga ctcagagctg gtcgcacact gtgcctccct cctcaccgcc 180 catcgtaatg aattattttg aaaattaatt ccaccatcct ttcagattct ggatggaaag 240 actgaatctt tgactcagaa ttgtttgctg aaaagaatga tgtgactttc ttagtcattt 300-301
< 210 > 250 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 250 ggtctgtgac aaggacttgc aggctgtggg aggcaagtga cccttaacac tacacttctc 60 cttatcttta ttggcttgat aaacataatt atttctaaca ctagcttatt tccagttgcc 120 cataagcaca tcagtacttt tctctggctg gaatagtaaa ctaaagtatg gtacatctac 180 ctaaaagact actatgtgga ataatacata ctaatgaagt attacatgat ttaaagacta 240 caataaaacc aaacatgctt ataacattaa gaaaaacaat aaagatacat gattgaaacc 300-301
< 210 > 251 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 251 gccgaggtcc tacatttggc ccagtttccc cctgcatcct ctccagggcc cctgcctcat 60 agacaacctc atagagcata ggagaactgg ttgccctggg ggcaggggga ctgtctggat 120 ggcaggggtc ctcaaaaatg ccactgtcac tgccaggaaa tgcttctgag cagtacacct 180 cattgggatc aatgaaaagc ttcaagaaat cttcaggctc actctcttga aggcccggaa 240 cctctggagg ggggcagtgg aatcccagct ccaggacgga tcctgtcgaa aagatatcct 300 c '301
< 210 > 252 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 252 gcaaccaatc actctgtttc acgtgacttt tatcaccata caatttgtgg catttcctca 60 ttttctacat tgtagaatca agagtgtaaa taaatgtata tcgatgtctt caagaatata 120 ttcactagga tcattccttt acccattcaa aatataagtc atatcaacaa aagaatctta 180 atatatcaag caaactggaa ggcagaataa ctaccataat ttagtataag tacccaaagt 240 aaaagcccta tttataaatc atgataacca tcaatcatca tttttagaat ctgtagaatc 300-301
< 210 > 253 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 253 ttccctaaga agatgttatt ttgttgggtt ttgttccccc tccatctcga ttctcgtacc 60 aaaaaaataa caactaaaaa agaaaaaatg tgctgcgttc tgaaaaataa ctccttagct 120 tggtctgatt gttttcagac cttaaaatat aaacttgttt cacaagcttt aatccatgtg 180 gatttttttt cttagagaac cacaaaacat aaaaggagca agtcggactg aatacctgtt 240 tccatagtgc ccacagggta ttcctcacat tttctccata ggaaaatgct ttttcccaag 300 g 301
< 210 > 254 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 254 cgctgcgcct ttcccttggg ggaggggcaa ggccagaggg ggtccaagtg cagcacgagg 60 attcccttga aacttgacca agcgggtggg ttaaaccctg taaatgggaa caaaatcccc 120 ccaaatctct tcatcttacc ctggtggact cctgactgta gaattttttg gttgaaacaa 180 gaaaaaaata aagctttgga cttttcaagg ttgcttaaca ggtactgaaa gactggcctc 240 acttaaactg agccaggaaa agctgcagat ttattaatgg gtgtgttagt gtgcagtgcc 300 t 301
< 210 > 255 < 211 > 302 < 212 > DNA < 213 > Homo sapien < 400 > Tttttttttt tttttttttt 255 agcttttttt ttcattaaaa aatagtgctc tttattataa 60 attactgaaa tgtttctttt ctgaatataa atataaatat gtgcaaagtt tgacttggat 120 tgggattttg ttgagttctt caagcatctc ctaataccct caagggcctg agtagggggg 180 aggaaaaagg actggaggtg gaatctttat aaaaaacaag agtgattgag gcagattgta 240 aaaaacaaga aacattatta aaaatagaga aacaaacaaa aaaaaaccac cccaacacac 300 aa 302
< 210 > 256 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 256 gttccagaaa acattgaagg tggcttccca aagtctaact agggataccc cctctagcct 60 aggac CTCC tccccacacc tcaatccacc aaaccatcca taatgcaccc agataggccc 120 acccccaaaa gcctggacac cttgagcaca cagttatgac caggacagac tcatctctat 180 aggcaaatag ctgctggcaa actggcatta cctggtttgt ggggatgggg gggcaagtgt 240 gtggcctctc ggcctggtta gcaagaacat tcagggtagg cctaagttan tcgtgttagt 300 t 301 < 210 > 257 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 257 gttgtggagg aactctggct tgctcattaa gtcctactga ttttcactat cccctgaatt 60 tccccactta tttttgtctt tcactatcgc aggccttaga agaggtctac ctgcctccag 120 tcttacctag tccagtctac cccctggagt tagaatggcc atcctgaagt gaaaagtaat 180 gtcacattac tcccttcagt gatttcttgt agaagtgcca atccctgaat gccaccaaga 240 tcttaatctt cacatcttta atcttatctc tttgactcct ctttacaccg gagaaggctc 300 c 301 < 210 > 258 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 258 cagcagtagt agatgccgta tgccagcacg cccagcactc ccaggatcag caccagcacc 60 aggggcccag ccaccaggcg cagaagcaag ataaacagta ggctcaagac cagagccacc 120 caagaatcca cccagggcaa ataccaggac tgggcaaaat cttcaaagat cttaacactg 180 atgtctcggg cattgaggct gtcaataana cgctgatccc ctgctgtatg gtggtgtcat 240 tggtgatccc tgggagcgcc ggtggagtaa cgttggtcca tggaaagcag cgcccacaac 300 t 301
< 210 > 259 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 259 tcatatatgc aaacaaatgc agactangcc tcaggcagag actaaaggac atctcttggg 60 gtgatttgga gtgtcctgaa cccctgaggg cagacaccta agtaggaatc ccagtgggaa 120 gcaaagccat aaggaagccc aggattcctt gtgatcagga agtgggccag gaaggtctgt 180 tccágctcac atctcatctg catgcagcac ggaccggatg cgcccactgg gtcttggctt 240 ttctcaagca ccctcccatc gtgtccttgt tgagccattt gcatccttgg ctccaggtgg 300 c 301
< 210 > 260 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 260 ttttttttct ccctaaggaa aaagaaggaa caagtctcat aaaaccaaat aagcaatggt 60 aaggtgtctt aacttgaaaa agattaggag tcactggttt attgaatgaa acaagttata 120 agaactgtaa cagccacagt tggccatttc atgccaatgg cagcaaacaa caggattaac 180 tagggcaaaa taaataagtg tgtggaagcc ctgataagtg cttaataaac agactgattc 240 actgagacat cagtacctgc ccgggcggcc gctcgagccg aattctgcag atatccatca 300 c 301
< 210 > 261 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 261 aaatattcga gcaaatcctg taactaatgt aaggctttga gtctccataa actcagtgaa 60 tctgcttcca tccacgattc tagcaatgac ctctcggaca tcaaagctcc tcttaaggtt 120 attccataca agcaccaact attcatcagc aggaaataaa ggctcttcag aaggttcaat 180 ggtgacatcc aatttcttct gataatttag attcctcaca accttcctag ttaagtgaag 240 ggcatgatga tcatccaaag cccagtggtc acttactcca gactttctgc aatgaagatc 300-301
< 210 > 262 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 262 tgttacagca gaggagagcc tttgtaagca cagaatactc caggagtatt tgtaattgtc 60 tgtgagcttc ttgccgcaag tctctcagaa atttaaaaag atgcaaatcc ctgagtcacc 120 cctagacttc ctaaaccaga tcctctgggg ctggaacctg tttgtaatga gcactctgca 180 gggctttctg gtgcacacct aattttgtgc atctttgccc taaatcctgg attagtgccc 240 catcattacc cccacattat aatgggatag attcagagca gatactctcc agcaaagaat 300 c 301
< 210 > 263 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > Character that is diverse < 222 > ( 1 ) . . . (301) < 223 > n = A, T, C or G < 400 > 263 tttagcttgt ggtaaatgac tcacaaaact gattttaaaa tcaagttaat gtgaattttg 60 cttaatccta aaaattacta attcacaata acaatggcat taaggtttga cttgagttgg 120 ttcttagtat tatttatggt aaataggctc ttaccacttg caaataactg gccacatcat 180 taatgactga cttcccagta aggctctcta aggggtaagt angaggatcc acaggatttg 240 agatgctaag gccccagaga tcgtttgatc caaccctctt attttcagag gggaaaatgg 300 g 301
< 210 > 264 < 211 > 301 < 212 > DNA < 213 > Homo sapi in < 400 > 264 aaccactcta aaagacgtta ctaccacttg tggaactctc aaagggtaaa tgacaaas 60 cc aatgaatgac tctaaaaaca atatttacat ttaatggttt gtagacaata aaaaaacaag 120 gtggatagat ctagaattgt aacattttaa scatttgaca gaaaaccata gatgagaaag 180 ctcaattata gatgcaaagt tataactaaa ctactatagt agtaaagaaa tacatttcac 240 acccttcata taaattcact atcttggctt gaggcactcc ataaaatgta tcacgtgcat 300-301
< 210 > 265 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 265 tgcccaagtt atgtgtaagt gtatccgcac ccagaggtaa aactacactg tcatctttgt 60 cttcttgtga cgcagtattt cttctctggg gagaagccgg gaagtcttct ectggctcta 120 catattcttg gaagtctcta atcaactttt gttccatttg tttcatttct tcaggaggga 180 ttttcagttt gtcaacatgt tctctaacaa tttctgtaaa cacttgccca gaatccaaag 240 cagtccaagg ctttgacatg tcaacaacca gcataactag agtatccttc agagatacgg 300 c 301 < 210 > 266 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 266 taccgtctgc ccttcctccc atccaggcca tctgcgaatc tacatgggtc ctcctattcg 60 acaccagatc actctttcct ctacccacag gcttgctatg agcaagagac acaacctcct 120 ctcttctgtg ttccagcttc ttttcctgtt cttcccaccc cttaagttct attcctgggg 180 atagagacac caatacccat aacctctctc ctaagcctcc ttataaccca gggtgcacag 240 cacagactcc tgacaactgg taaggccaat gaactgggag ctcacagctg gctgtgcctg 300-301
< 210 > 267 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 267 aaagagcaca ggccagctca gcctgccctg gccatctaga ctcagcctgg ctccatgggg 60 gttctcagtg ctgagtccat ccaggaaaag ctcacctaga ccttctgagg ctgaatcttc 120 atcctcacag gcagcttctg agagcctgat attcctagcc ttgatggtct ggagtaaagc 180 ctcattctga ttcctctcct tcttttcttt caagttggct ttcctcacat ccctctgttc 240 aattcgcttc agcttgtctg ctttagccct catttccaga agcttcttct ctttggcate 300 t 301
< 210 > 268 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 268 aatgtctcac tcaactactt cccagcctac cgtggcctaa ttctgggagt tttcttctta 60 gatcttggga gagctggttc ttctaaggag aaggaggaag gacagatgta actttggatc 120 tcgaagagga agtctaatgg aagtaattag tcaacggtcc ttgtttagac tcttggaata 180 tgctgggtgg ctcagtgagc ccttttggag aaagcaagta ggagtaacca ttattcttaa 240 cttcccattg ttctactttc taccatcatc aattgtatat tatgtattct ttgcagaact 300-301 < 210 > 269 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 269 taacaatata cactagctat ctttttaact gtccatcatt agcaccaatg aagattcaat 60 aaaattacct ttattcacac atctcaaaac aattctgcaa attcttagtg aagtttaact 120 atagtcacag accttaaata ttcacattgt tttctatgtc tactgaaaat aagttcacta 180 cttttctgga tattctttac aaaatcttat taaaattcct ggtattatca cccccaatta 240 tacagtagca caaccacctt atgtagtttt tacatgatag ctctgtagaa gtttcacatc 300 t 301
< 210 > 270 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 270 cattgaagag cttttgcgaa acatcagaac acaagtgctt ataaaattaa ttaagcctta 60 cacaagaata catattcctt ttatttctaa ggagttaaac atagatgtag ctgatgtgga 120 gagcttgctg gtgcagtgca tattggataa cactattcat ggccgaattg atcaagtcaa 180 ccaactcctt gaactggatc atcagaagaa gggtggtgca cactagataa cgatatactg 240 tggaccaacc aactaaattc tctcaccagg ctgtatcagt aaactggctt aacagaaaac 300-301
< 210 > 271 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 271 aaaaggttct cataagatta acaatttaaa taaatatttg atagaacatt ctttctcatt 60 tttatagctc atctttaggg ttgatattca gttcatgctt cccttgctgt tcttgatcca 120 cacttcatca gaattgcaat gcctgtattc gctccaattc tctataaagt gggtccaagg 180 tgaaccacag agccacagca cacctctttc ccttggtgac tgccttcacc ccatganggt 240 tctctcctcc agatganaac tgatcatgcg cccacatttt gaagcagtca gggttttata 300 c 301 < 210 > 272 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 272 taaattgcta asccacagat aacaccaatc aaatggaaca aatcactgtc ttcaaatgtc 60 ttatcagaaa accaaatgag cctggaatct tcataatacc taaacatgcc gtatttagga 120 tccaataatt ccctcatgat gagcaagaaa aattctttgc gcacccctcc tgcatccaca 180 catcttctc caacaaatat aaccttgagt ggcttcttgt aatctatgtt ctttgttttc 240 ctaaggactt ccattgcatc tcctacaata ttttctctac gcaccactag aattaagcag 300
? "301
< 210 > 2 ^ 3 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 273 acatgtgtgt atgtgtatct ttgggaaaan aanaagacat cttgtttayt atttttttgg 60 agagangctg ggacatggat aatcacwtaa tttgctayta tyactttaat ctgactygaa 120 gaaccgtcta aaaataaaat ttaccatgtc dtatattcct tatagtatgc ttatttcacc 180 ttytttctgt ccagagagag tatcagtgac ananattt to gggtgaamac atgmattggt 240 gggacttnty tttacngagm accctgcccg sgcgccctcg makcngantt ccgcsananc 300 t 301
< 210 > 274 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 274 cttatatact ctttctcaga ggcaaaagag gagatgggta atgtagacaa ttctttgagg 60 aacagtaaat gattattaga gagaangaat ggaccaagga gacagaaatt aacttgtaaa 120 tgattctctt tggaatctga atgagatcaa gaggccagct ttagcttgtg gaaaagtcca 180 tctaggtatg gttgcattct cgtcttcttt tctgcagtag ataatgaggt aaccgaaggc 240 aattgtgctt cttttgataa gaagctttct tggtcatatc aggaaattcc aganaaagtc 300 c 301
< 210 > 275 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 275 tcggtgtcag cagcacgtgg cattgaacat tgcaatgtgg agcccaaacc acagaaaatg 60 gggtgaaatt ggccaacttt ctattaactt atgttggcaa ttttgccacc aacagtaagc 120 tggcccttct aataaaagaa aattgaaagg tttctcacta aacggaatta agtagtggag 180 tcaagagact cccaggcctc agcgtacctg cccgggcggc cgctcgaagc cgaattctgc 240 agatatccat cacactggcg gncgctcgan catgcatcta gaaggnccaa ttcgccctat 300-301
< 210 > 276 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 276 tgtacacata ctcaataaat aaatgactgc attgtggtat tattactata ctgattatat 60 ttatcatgtg acttctaatt agaaaatgta tccaaaagca aaacagcaga tatacaaaat 120 taaagagaca gaagatagac attaacagat aaggcaactt atacattgag aatccaaatc 180 caatacattt aaacatttgg gaaatgaggg ggacaaatgg aagccagatc aaatttgtgt 24 0 aaeactattc agtatgtttc ccttgcttca tgtctgagaa ggctctcctt caatgggcat 300 g 301 < 2 10 > 277 < 21 1 > 301 < 212 > DNA < 2 1 3 > Homo sapi in < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 277 tttgttgatg tcagtatttt attacttgcg ttatgagtgc tcacctggga aattctaaag 60 cttggaggaa atacagagga gcagagcaac tgaatttaat ttaaaagaag gaaaacattg 120 actcctgata gaatcatgsc ctttcccaaa tcaacactct caatgcccca ccctcgtcct 180 caccatagtg gggagactaa agtggccacg gatttgcctt angtgtgcag tgcgttctga 240 gttcnctgtc gattacatct gaccagtctc ctttttccga agtccntccg ttcaatcttg 300 c 301 < 210 > 278 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) F
< 223 > n = A, T, C or G < 400 > 278 taccactaca ctccagcctg ggcaacagag caagacctgt ctcaaagcat aaaatggaat 60 aacatatcaa atgaaacagg gaaaatgaag ctgacaattt atggaagcca gggcttgtca 120 cagtctctac tgttattatg cattacctgg gaatttatat aagcccttaa taataatgcc 180 aatgaacatc tcatgtgtgc tcacaatgtt ctggcactat tataagtgct tcacaggttt 240 tatgtgttct tcgtaacttt atggantagg tactcggccg cgaacacgct aagccgaatt 300 c 301 < 210 > 279 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 279 aaagcaggaa tgacaaagct tgcttttctg gtatgttcta ggtgtattgt gacttttact 60 gttatattaa ttgccaatat aagtaaatat agattatata tgtatagtgt ttcacaaagc 120 ttagaccttt accttccagc caccccacag tgcttgatat ttcagagtca gtcattggtt 180 atacatgtgt agttccaaag cacataagct agaar.aanaa atatttctag ggagcactac 240 catctgtttt cacatgaaat gccacacaca tacaactcca acatcaattt cattgcacag 300 to '301 < 210 > 280 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 280 ggtactggag ttttcctccc ctgtgaaaac gtaactactg ttgggagtga attgaggatg 60 tagaaaggtg gtggaaccaa attgtggtca atc aaatag gagaatatgg ttctcactct 120 tgagaaaaaa acctaagatt agcccaggta gttgcctgta acttcagttt ttctgcctgg 180 F gtttgatata gtttagggtt ggggttagat taagatctaa attacatcag gacaaagaga 240 cagactatta actccacagt taattaagga ggtatgttcc atgtttattt gttaaagcag 300 t 301 < 210 > 281 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 281 ct aggtacaaga aggggaatgg gaaagagctg ctgtggc attgttcaac ttggatattc 60 gccgagcaat ccaaatcctg aatgaagggg catcttctga aaaaggagat ctgaatctca 120 aatggcttta atgtggtagc cggatgagaa tcgggttata tggagagaaa gaactccctt 180 tgtgtagcac actgcgatta cagctaaata acccgtattt gtgtgtcatg tttgcatttc 240 tgacaagtga aacaggatct tacgatggag ttttgtatga aaacaaagtt gcagtacctc 300301 < 210 > 282 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 282 caggtactac agaattaaaa tactgacaag caagtagttt cttggcgtgc acgaattgca 60 tccagaaccc aaaaattaag aaattcaaaa agacattttg tgggcacctg ctagcacaga 120 agcgcagaag caaagcccag gcagaaccat gctaacctta cagctcagcc tgcacagaag 180 cgcagaagca aagcccaggc agaaccatgc taaccttaca gctcagcctg cacagaagcg 240 cagaagcaaa gcccaggcag aacatgctaa ccttacagct cagcctgcac agaagcacag 300-301 < 210 > 283 < 211 > 301 < 212 > DNA F < 213 > Homo sapien < 400 > 283 atctgtatac ggcagacaaa ctttatarag tgtagagagg tgagcgaaag gatgcaaaag 60 cactttgagg gctttataat aatatgctgc ttgaaaaaaa aaatgtgtag ttgatactca 120 gtgcatctcc agacatagta aggggttgct ctgaccaatc aggtgatcat tttttctatc 180 acttcccagg ttttatgcaa aaattttgtt aaattctata atggtgatat gcatctttta 240 ggaaacatat acatttttaa aaatctattt tatgtaagaa ctgacagacg aatttscttt 300
"301 <210> 284 <211> 301 <212> DNA <213> Homo sapien <400> 284 caggtacaaa acgctattaa gtggcttaga atttgaacat ttgtggtctt tatttacttt 60 gcttcgtgtg tgggcaaagc aacatcttcc ctaaatatat attaccaaga aaagcaagaa 120 gcagattagg tttttgacaa aacaaacagg ccaaaagggg gctgacctgg agcagagcat 180 ggtgagaggc aaggcatgag agggcaagtt tgttgtggac agatctgtgc ctactttatt 240 actggagtaa aagaaaacaa agttcattga tgtcgaagga tatatacagt gttagaaatt 300 a 301
< 210 > 285 < 211 > 301 < 212 > DNA < 213 > Homo sapien - • "
< 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 285 acatcaccat gatcggatcc cccacccatt atacgttgta tgtttacata aatactcttc 60 aataatcatt agtgttttaa aaaaaatact gaaaactcct tctgcatccc aatctctaac 120 caggaaagca aatgctattt acagacctgc aagccctccc tcaaacnaaa ctatttctgg 180 attaaatatg tctgacttct tttgaggtca cacgactagg caaatgctat ttacgatctg 240 caaaagctgt ttgaagagtc aaagccccca tgtgaacacg atttctggac cctgtaacag 300 t 301
< 210 > 286 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 286 taccactgca ttccagcctg ggtgacagag tgagactccg tctccaaaaa aaactttgct 60 tgtatattat ttttgcctta cagtggatca ttctagtagg aaaggacagt aagatttttt 120 atcaaaatgt gtcatgccag taagagatgt tatattcttt tctcatttct tccccaccca 180 aaaataagct accatatagc ttataagtct caaatttttg ccttttacta aaatgtgatt 240 gtttctgttc attgtgtatg cttcatcacc tatattaggc aaattccatt ttttcccttg 300 t 301
< 210 > 287 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 287 tacagatctg ggaactaaat attaaaaatg agtgtggctg gatatatgga gaatgttggg 60 cccagaagga acgtagagat cagatattac aacagctttg ttttgagggt taaaaatatg 120 aaatgatttg gttatgaacg cacagtttag gcagcagggc cagaatcctg accctctgcc 180 ccgtggttat ctcctcccca gcttggctgc ctcatgttat cacagtattc cattttgttt 240 attscatct c ttgtgaagcc atcaagattt tctcgt ta'c tc tt 300 t ctctca ttgqtaa aka " '301 < 210> 288 <2 1 1> 301 <2 12> DNA <2 1 3> Homo sapien <400> 288 gtacacctaa ctgcaaggac agctgaggaa tgtaatgggc agccgctttt aaagaagtag 60 agtcaatagg aagacaaatt ccagttccag ctcagtctgg gtatctgcaa agctgcaaaa 120 gatctttaaa gacaatttca agagaatatt tccttaaagt tggcaatttg gagatcatac 180 aaaagcatct gcttttgtga tttaatttag ctcatctggc cactggaaga atccaaacag 240 tctgccttaa ttttggatga atgcatgatg gaaattcaat aatttagaaa gttaaaaaaa 300 to 301"< 210 > 289 < 211 > 301 < 212 > DNA F < 213 > Homo sapien < 220 > < 221 > different characteristic < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 289 ggtacactgt ttccatgtta tgtttctaca cattgctacc tcagtgctcc tggaaactta 60 gcttttgatg tctccaagta gtccaccttc atttaactct ttgaaactgt atcatctttg 120 ccaagtaaga gtggtggcct atttcagctg ctttgacaaa atgactggct cctgacttaa 180 cgttctataa atgaatgtgc tgaagcaaag tgcccatggt ggcggcgaan aagagaaaga 240 tgtgttttat tttggactct ctgtggtccc ttccaatgct gtgggtttcc aaccagngga 300 to '301 < 210 > 290 < 211 > 301 < 212 > DNA F
< 213 > Homo sapien < 220 > < 221 > different characteristic < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 290 cttcttgata acactgagct aatatacaga atgcttggca tatacaagat tctatactac 60 tgactgatct gttcatttct ctcacagctc ttacccccaa aagcttttcc accctaagtg 120 ttctgacctc cttttctaat cacagtaggg atagaggcag anccacctac aatgaacatg 180 gagttctatc aagaggcaga aacagcacag aatcccagtt ttaccattcg ctagcagtgc 240 tgccttgaac aaaaacattt ctccatgtct cattttcttc atgcctcaag taacagtgag 300-301 < 210 > 291 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 291 tttcttctat caggtaccaa cctagaaaca tttcatttta tgttgttgaa acataacaac 60 tatatcagct agattttttt tctatgcttt acctgctatg gaaaatttga cacattctgc 120 tttactcttt tgtttatag tgaatcacaa aatgtatttt tatgtattct gtagttcaat 180 agccatggct gtttacttca tttaatttat ttagcataaa gacattatga aaaggcctaa 240 cacttcccca acatgaactt ctaactaatt agcatctgtt atttcttaac cgtaatgcct 300 to "301 < 210 > 292 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > miscellaneous feature - < 222 > (1) ... (301) < 223 > n = A, T, C or GF
< 400 > 292 accttttagt agtaatgtct aataataaat aagaaatcaa ttttataagg tccatatagc 60 tgtattaaat aatttttaag tttaaaagat aaaataccat cattttaaat gttggtattc 120 aaaaccaaag natataaccg aaaggaaaaa cagatgagac ataaaatgat ttgcnagatg 180 ggaaatatag tasttyatga atgttnatta aattccagtt ataatagtgg ctacacactc 240 cacagacccc tcactacaca atgccacaaa acagtcctat taacttgaaa cacatttcca 300-301 < 210 > 293 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 293 ggtaccaagt gctggtgcca gcctgttacc tgttctcact gaaaagtctg gctaatgctc 60 ttgtgtagtc acttctgatt ctgacaatca atcaatcaat ggcctagagc actgactgtt 120 aacacaaacg tcactagcaa agtagcaaca gctttaagtc taaatacaaa gctgttctgt 180 gtgagaattt tttaaaaggc tacttgtata ataacccttg tcatttttaa tgtacctcgg 240 gctaagccga ccgcgaccac attctgcaga tatccatcac actggcggcc gctcgagcat 300 g 301 < 210 > 294 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 294 tgacccataa caatatacac tagctatctt tttaactgtc catcattagc accaatgaag 60 attcaataaa attaccttta ttcacacatc tcaaaacaat tctgcaaatt cttagtgaag 120 tttaactata gtcacaganc ttaaatattc acattgtttt ctatgtctac tgaaaataag 180 ttcactactt ttctgggata aatcttatta ttctttacaa aaattcctgg tattatcacc 240 cagtagcaca cccaattata accaccttat gtagttttta catgatagct ctgtagaggt 300 t 301 <; 210 > 295 < 2I1 > 305 < 212 > DNA < 213 > Homo sapien < 400 > 295 gtactctttc tctcccctcc tctgaattta attctttcaa cttgcaattt gcaaggatta 60 cacatttcac tgtgatgtat attgtgttgc aaaaaaaaaa gtgtctttgt ttaaaattac 120 ttggtttgtg aatccatctt gctttttccc cattggaact agtcattaac ccatctctga 180 actggtagaa aaacrtctga agagctagtc tatcagcatc tgacaggtga attggatggt 240 tctcagaacc atttcaccca gacagcctgt ttctatcctg tttaataaat tagtttgggt tctct 300 305 < 210 > 296 < 211 > 301 < 212 > DNA < 213 > Homo sapien F
< 400 > 296 aggtactatg ggaagctgct aaaataatat ttgatagtaa aagtatgtaa tgtgctatct 60 taaactaaaa cacctagtag actttatgga ataaactgaa atctgaagtt attttccttg 120 attaaataga attaataaac caatatgagg aaacatgaaa ccatgcaatc tactatcaac 180 tttgaaaaag tgattgaacg aaccacttag ctttcagatg atgaacactg ataagtcatt 240 tgtcattact ataaatttta aaatctgtta ataagatggc ctatagggag gaaaaagggg 300 c 301 < 210 > 297 < 211 > 300 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (300) < 223 > n = A, T, C or G < 400 > 297 actgagtttt aactggacgc caagcaggca aggctggaag gttttgctct ctttgtgcta 60 aaaccttgaa aaggttttga ggagaatcat tttgacaaga agtacttaag agtctagaga 120 acaaagangt gaaccagctg aaagctctcg ggggaanctt acatgtgttg ttaggcctgt 180 tccatcattg ggagtgcact ggccatccct caaaatttgt ctgggctggc ctgagtggtc 240 accgcacctc ggccgcgacc acgctaagcc gaattctgca gatatccatc acactggcgg 300 < 210 > 298 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (301) F
< 223 > n = A, T, C or G < 400 > 298 tatggggttt gtcacccaaa agctgatgct gagaaaggcc tccctggggc ccctcccgcg 60 ggcatctgag agacctggtg ttccagtgtt tctggaaatg ggtcccagtg ccgccggctg 120 tgaagctctc agatcaatca cgggaagggc ctggcggtgg tggccacctg gaaccaccct 180 gtcctgtctg tttacatttc actaycaggt tttctctggg cattacnatt tgttccccta 240 caacactgac ctgtgcattc tgctctsgcc tgctgtgtct gcaggtggct ctcagcgagg 300 t "301 < 210 > 299 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 299 gttttgagac ggagtttcac tcttgttgcc cagactggac tgcaatggca gggtctctgc 60 tcactgcacc ctctgcctcc caggttcgag caattctcct gcctcagcct cccaggtagc 120 tgggattgca ggctcacgcc accataccca gctaattttt ttgtattttt agtagagacg 180 gagtttcgcc atgttggcca gctggtctca aactcctgac ctcaagcgac ctgcctgcct 240 aagtgctgga cggcctccca attataggca tgagtcaaca cgcccagcct aaagatattt 300 t 301 <210> 300 F <211> 301 <212> DNA <213> Homo sapien <400> 300 attcagtttt atttgctgcc ccagtatctg taaccaggag tgccacaaaa tc ttgccaga 60 tatgtcccac acccactggg aaaggctccc acctggctac ttcctctatc agctgggtca 120 gctgcattcc acaaggttct cagcctaatg agtttcacta cctgccagtc tcaaaactta 180 gtaaagcaag accatgacat tcccccacgg aaatcagagt ttgccccacc gtcttgttac 240 tataaagcct gcctctaaca gtccttgctt cttcacacca atcccgagcg catcccccat 300 g 301 < 210 > 301 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 301 ttaaattttt gagaggataa aaaggacaaa taatctagaa atgtgtcttc ttcagtctgc 60 agaggacccc aggtctccaa gcaaccacat ggtcaagggc atgaataatt aaaagttggt 120 gggaactcac aaagaccctc agagctgaga cacccacaac agtgggagct cacaaagacc 180 ctcagagctg agacacccac aacagtggga gctcacaaag accctcagag ctgagacacc 240 cacaacagca cctcgttcag ctgccacatg tgtgaataag gatgcaatgt ccagaagtgt 300 t 301 < 210 > 302 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 302 aggtacacat ttagcttgtg gtaaatgact cacaaaactg attttaaaat caagttaatg 60 tgaattttga aaattactac ttcacaataa ttaatcctaa caatggcatt aaggtttgac 120 ttgagttggt tcttagtatt atttatggta aataggctct taccacttgc aaataactgg 180 F ccacatcatt aatgactgac ttcccagtaa ggctctctaa ggggtaagta ggaggatcca 240 caggatttga gatgctaagg ccccagagat cgtttgatcc aaccctctta ttttcagagg 300 g 301 < 210 > 303 < 2il > 301 < 212 > DNA < 213 > Homo sapien < 400 > 303 AGGTA ccaac tgtggaaata ggtagaggat cattttttct ttccatatca actaagttgt 60 atatt jtttt ttgacagttt aacacatctt cttctgtcag agattctttc acaatagcac 120 TIGCC _ aatgg aactaccgct tgcatgttaa aaatggtggt ttgtgaaatg atcataggcc 180 agta cgggt atgtttttct aactgatctt ttgctcgttc caaagggacc tcaagacttc 240 catcggatttt atatctggga tctagaaaag gagttaatct gttttccctc ataaattcac 300 c 301 < 210 > 304 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 400 > 304 acatggatgt tattttgcag actgtcaacc tgaatttgta tttgcttgac attgcctaat 60 F tattagtttc agtttcagct tacccacttt ttgtctgcaa catgcaraas agacagtgcc 120 ctttttagtg tatcatatca ggaatcatct cacattggtt tgtgccatta ctggtgcagt 180 gactttcagc cacttgggta aggtggagtt ggccatatgt ctccactgca aaattactga 240 ttttcctttt gtaattaata agtgtgtgtg tgaagattct ttgagatgag gtatatatct 300 c 301 <; 210 > 305 < 211 > 301 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (301) < 223 > n = A, T, C or G < 400 > 305 gangtacagc gtggtcaagg taacaagaag aaaaaaatgt gagtggcatc ctgggatgag 60 gacctggaca cagggggaca gacacgttgt catttgctgc tgtgggtagg aaaatgggcg 120 gaaacagata taaaggagga caaaatctcc aactcagtat taaggtattc tcatgcctag 180 aatattggta gaaacaagaa tacattcata tggcaaataa tggaacaaaa ctaaccatgg 240 ttctgggatt taagttggat accaangaaa ttgtattaaa agagctgttc atggaataag 300-301 < 210 > 306 < 211 > 8 < 212 > PRT < 213 > Homo sapien < 400 > 306 Go l Leu Gly Trp Val Wing Glu Leu 1 5 F
< 210 > 307 < 211 > 637 < 212 > DNA < 213 > Homo sapien < 400 > 307 acacccratg aacggasa? c cagacgatga ggaagcccccctgccgattt gctttcotcc 60 ttgtcatcag gtggtctatt cggcttatcc ctacaaagaa gaatcca aa atag CCAC 120 attgaggaat gatacttgeg cccaaagagc attcaatcat tgttttattt gtcttmtttt 180 cacaccattg gtgaggga g gattaccacc ctggggttat gaagatggtt gaacacccca 240 cacatagcac cggagatatg agatcaacag tttcttagcc atagagattc acagcccaga 300 gcaggaggac gcttgcacac catgcaggat gacatggggg atgcgctcgg gattggtgtg 360 gactgttaga aagaagcaag ggcaggcttt atagtaacaa caaactctga gacggtgggg 420 tttccgtggg ggaatgtcat ggtcttgctt tactaagttt tgagactggc aggtagtgaa 480 actcattagg ctgagaacct tgtggaatgc acttgaccca sctgatagag gaagtagcca 540 ggtgcgagcc tttcccagtg ggtgtgggac atatctggca agattttgtg gcactcctgg 600 ttacagatac tggggcagca aataaaactg aatcttg 637 < 210 > 308 < 211 > 647 < 212 > DNA < 213 > Homo sapien < 220 > < 221à > diverse feature F < 222 > (1) ... (647) < 223 > n = A, T, C or G < 400 > 308 ttatcatgta acgattttca aatcgggtca ctcaaggggc caaccacagc tgggagccac 60 tgctcagggg aaggttcata tgggactttc tactgcccaa ggttctatac aggatataaa 120 ggngcctcac agtatagatc gaagaagaaa tggtagcaaa caaacactga tctctttctg 180 ccacccctct gaccctttgc aactcctctg accctttaga acaagcctac ctaatatctg 240 ctagagaaaa gaccaacaac ggcctcaaag gatctcttac catgaaggtc tcagctaatt 300 cttggctaag atgtgggttc cacattaggt tctgaatatg gggggaaggg tcaatttgct 360 cattttgtgt gtggataaag tcaggatgcc caggggccag agcagggggc tgcttgcttt 420 gggaacaatg gctgagcata taaccatagg ttatggggaa caaaacaaca tcaaagtcac 480 tgtatcaatt gccatgaaga cttgagggac ctgaatctac cgattcatct taaggcagca 540 ggaccagttt gagtggcaac aatgcagcag cagaatcaat ggaaacaaca gaatgattgc 600 aatgtccttt tttttctcct gcttctgact tgataaaagg ggaccgt 647 < 210 > 309 < 211 > 460 < 212 > DNA < 213 > Homo sapien < 400 > 309 ttaggctgga actttatagt cattggaaaa aaaaaaaagc cagaacaaca tgtgatagat 60 aatatgattg gctgcacact tgaatgatga tccagactga acgtgatgga ctattgtatg 120 gagcacatct tcagcaagas ggggaaatac tcatcatttt tggccagcag ttgtttgatc 180 accaaacatc atgccagaat actcagcaaa ccttcttagc tcttgagaag tcaaagtccg 240 ttcctggcaa ggggaattta ttttaattgg actccttatg tgagagcagc ggctacccag 300 ctggggtggt ggagcgaacc cgtcactagt ggacatgcag tggcagagct cctggtaacc 360 atacacaggc acctagagga acatgtgtga tgccaagcgt gacacctgta gcactcaaat 420 ttgtcttgtt tttgtctttc ggtgtgtaag attcttaagt 460 < 210 > 310 < 211 > 539 < 212 > DNA < 213 > Homo sapien < 400 > 310 acgggactta tcaaataaag ataggaaaag aagaaaactc aaatattata ggcagaaatg 60 ctaaaggttt taaaatatgt caggattgga agaaggcatg gataaagaac aaagttcagt 120 tasaaaagag to attacks aa ggaagagaca caataaaagt tatgta ca tctgtgacaa 380 gtcagacagt aa atttgtg ggaaatgggt tggtttgttg tatggtatgt attttagcaa 240 taatctttat ggtagagaaa gctaaaatcc tttagcttgc tgaatgatc acttgctgaa 300 ttcctcaagg taggcatgat caaggagggt ttagaggaga cacagacaca atgaactgac 360 agtcttagta ctagatagaa tactcagcta ggaatagtga ttctgagggc acactgtgac 420 atgattatgt cattacatgt atggtagtga tggggatgat aggaaggaag aacttatggc 480 atattttcac ccccacaaaa gtcagttaaa tattgggaca ctaaccatcc aggtcaaga 539 < 210 > 311 < 211 > 526 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (526) < 223 > n = A, T, C or G < 400 > 311 caaatttgag ccaatgacat agaattttac aaatcaagaa gcttattctg gggccatttc 60 ttttgacgtt ttctctaaac tactaaagag gcattaatga tccataaatt atattatcta 120 catttacagc atttaaaat.g t.gt.t.cagcat. gaaat.at.t.ag ct.acagggga agct.aaat.aa 180 attaaacatg gaataaagat ttgtccttaa atataatcta caagaagact ttgatatttg 240 tttttcacaa gtgaagcatt cttataaagt gtcataacct ttttggggaa actatgggaa 300 aaaatgggga aactctgaag ggttttaagt atcttacctg aagctacaga ctccataacc 360 tctctttaca gggagctcct gcagccccta cagaaatgag tggctgagat tcttgattgc 420 acagcaagag cttctcatct aaaccctttc cctttttagt atctgtgtat caagtataaa 480 agttctataa actgtagtnt acttatttta atccccaaag cacagt 526 < 210 > 312 < 211 > 500 < 212 > DNA <; 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (500) < 223 > n = A, T, C or G < 400 > 312 cctctctctc cccaccccct gactctagag aactgggttt tctcccagta ctccagcaat 60 aascagttga tcatttctga gccactttat tccaaagtac actgcagatg ttcaaactct 120 ttcccttcca ccatttctct cctgccagtt ttgctgactc tcaacttgtc atgagtgtaa 180 gcattaagga cattatgctt cttcgattct gaagacaggc cctgctcatg gatgactctg 240 gcttcttagg aaaatatttt tcttccaaaa tcagtaggaa atctaaactt atcccctctt 300 tgcagatgtc tagcagcttc agacatttgg ttaagaaccc atgggaaaaa aaaaaatcct 360 tgctaatgtg gtttcctttg taaaccanga ttcttatttg nctggtatag aatatcagct 420 ctgaacgtgt ggtaaagatt tttgtgtttg aatataggag aaatcagttt gctgaaaagt 480 tagtcttaat tatctattgg 500 < 210 > 313 < 211 > 718 < 212 > DNA F < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1); "-18, < 223 > n = i, T, C or G < 400 > 313 ggagatttgt gtggtttgca gccgagggag accaggaaga tctgcatggt gggaaggacc € 0 tgatgataca gaggtgagaa ataagaaagg ctgctgactt taccatctga ggccacacat 120 ctgctgaaat ggagataatt aacatcacta gaaacagcaa taatgtctaa gatgacaata 180 gtagtgacat gtttttgcac atttccagcc cttttaaata tccacacaca caggaagcac 240 aaaaggaagc acagagatcc ctgggagaaa tgcccggccg ccatcttggg tcatcgatga 300 gcctcgccct stgcctgntc ccgcttgtga gggaaggaca ttagaaaatg aattgatgtg 360 ttccttaaag gatggcagga aaacagatcc tgttgtggat atttatttga acgggattac 420 tsaagtcaca agatttgaaa aagtgagcat taccaatgag aggaaaacag acgagaaaat 480 cttgatggtt cacaagacat gcaacaaaca aaatggaata ctgtgatgac acgagcagcc 540 aactggggag gagataccac ggggcagagg tcaggattct ggccctgctg cctaactgtg 600 atcatttcta cgttatacca tttctaccct caaacaagct gtngaatatc tgacttacgg 660 ttcttntggc ccacattttc atnatccacc ccntcntttt aannttantc caaantgt "18 < 210 > 314 < 211 > 358 < 212 > DNA < 213 > Homo sapien < 400 > 314 attacagaaa gtttatttac aaacatcaag ctatttcaaa acaatgtata tatatccata 60 tatagctgta cataatcaaa gtacatgttt tcattggtgt agattaccac aaatgcaagg ± 20 caacatgtgt asatctcttg tcttattctt ttgtctataa tactgtattg tgtagtccaa 180 gctctcggta gtccagccac tgtgaaacat gctcccttta gattaacctc gtggacgctc 240 ttgttgtatt gctgaactgt agtgccctgt attttgcttc tgtctgtgaa ttctgttgct 300 tctggggcat ttccttgtga tgcagaggac caccacacag atgacagcaa tctgaatt 358 < 210 > 315 < 211 > 341 < 212 > DNA < 213 > Homo sapien < 400 > 315 taccacctcc ccgctggcac tgatgagccg catcaccatg gtcaccagca ccatgaaggc 60 ataggtgatg atgaggacat ggaatgggcc cccaaggatg gtctgtccaa agaagcgagt 120 gacccccatt ctgaagatgt ctggaacctc taccagcagg atgatgatag ccccaatgac 180 agtcaccagc tccccgacca gccggatatc gtccttaggg gtcatgtagg cttcctgaag 240 tagcttctgc tgtaagaggg tgttgtcccg ggggctcgtg cggttattgg tcctgggctt 300 gagggggcgg tagatgcagc acatggtgaa gcagatgatg t 341 < 210 > 316 < 211 > 151 < 212 > DNA < 213 > Homo sapien < 400 > 316 agactgggca agactcttac gccccacact gcaatttggt cttgttgccg tatccattta 60 tgtgggcctt tctcgagttt ctgattataa acaccactgg agcgatgtgt tgactggact 120 cattcaggga gctctggttg caatattagt t 151 F
< 210 > 317 < 211 > 151 < 212 > DNA < 213 > Homo sapien < 400 > 317 agaactagtg gatcctaatg aaatacctga aacatatatt ggcatttatc aatggctcea 60 atcttcattt atctctggcc ttaaccctgg ctcctgaggc tcc gccagc a atcccagc 120 ccayggctct gttcttgcca cacctgcttg a 151 < 210 > 318 < 211 > 151 < 212 > DNA < 213 > Homo sapien < 400 > 318 actggtggga ggcgctgttt agttggctgt tttcagaggg gtctttcgga gggacctcct 60 gctgcaggct ggagtgtctt tattcctggc gggagaccgc acattccact gctgaggctg 120 tgggggcggt ttatcaggca gtgataaaca t 151 < 210 > 319 < 211 > 151 < 212 > DNA < 213 > Homo sapien < 400 > 319 aactagtgga tccagagcta taggtacagt gtgatctcag ctttgcaaac acattttcta 60 catagatagt actaggtatt aatagatatg taaagaaaga aatcacacca ttaataatgg 120 taagattggg tttatgtgat tttagtgggt a 151 < 210 > 320 < 211 > 150 < 212 > DNA < 213 > Homo sapien < 400 > 320 aactagtgga tccactagtc cagtgtggtg gaattccatt gtgttggggt tctagatcgc 60 gagcggctgc cctttttttt tttttttttg ggggggaatt tttttttttt aatagttatt 120 gagtgttcta cagcttacag taaataccat 150 < 210 > 321 F < 211 > 151 < 212 > DNA < 213 > Homo sapien < 400 > 321 agcaactttg tttttcatcc aggttatttt aggcttagga tttcctctca cactgcagtt 60 tagggtggca ttgtaaccag ctatggcata ggtgttaacc aaaggctgag taaacatggg 120 tgcctctgag aaatcaaagt cttcatacac t 151 < 210 > 322 < 211 > 151 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (151) < 223 > n = A, T, C or G < 400 > 322 attcascatc ttctcctgtt tcttgtcttc ctttttcttc ttcttasatt tccttcagg 60 tttgggcttg gtcagtttgc cacagggctt ggagatggtg acagtcttct ggca tcgsc 120 attgtgca g gctcgcttca nacttccagt t 251 < 210 > 323 < 211 > 151 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (151) < 223 > n = A, T, C or G < 400 > 323 tgaggacttg tkttcttttt ctttattttt aatcctctta ckttgtaaat atattgccta 60 nagactcant tactacccag tttgtggttt twtgggagaa atgtaactgg acagttagct 120 gttcaatyaa aaagacactt ancccatgtg g 151 < 210 > 324 < 211 > 4 61 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (461) < 223 > n = A, T, C or G < 400 > 324 acctgtgtgg aatttcagct ttcctcatgc aaaaggattt tgtatccccg gcctacttga 60 agaagtggtc agctaaagga atccaggttg ttggttggac tgttaatacc tttgatgaaa 120 agagttacta cgaatcccat cttggttcca gctatatcac tgacagcatg gtagaagact 180 gcgaacctca cttctagact ttcacggtgg gacgaaacgg gtccagaaac tgccaggggc 240 ctcatacagg gatatcaaaa taccctttgt gctacccagg ccctggggaa tcaggtgact 300 cacacaaatg caatagttgg tcactgcatt tttacctgaa ccaaagctaa acccggtgtt 360 gccaccatgc accatggcat gccagagttc aacactgttg ctcttgaaaa ttgggtctga 420 aaaaacgcac aagagcccct gccctgccct agctgangca c 461 < 210 > 325 < 211 > 400 < 212 > DNA < 213 > Homo sapien < 400 > 325 acactgtttc catgttatgt ttctacacat tgctacctca gtgctcctgg aaacttagct 60 tttgatgtct ccaagtagtc caccttcatt taactctttg aaactgtatc atctttgcca 120 agtaagagtg gtggcctatt tcagctgctt tgacaaaatg actggctcct gacttaacgt 180 tctataaatg aatgtgctga agcaaagtgc ccatggtggc ggcgaagaag agaaagatgt 240 gttttgtttt ggactctctg tggtcccttc caatgctgtg ggtttccaac caggggaagg 300 gtcccttttg cattgccaag tgccataacc atgagcacta cgctaccatg gttctgcctc 360 ctggccaagc aggctggttt gcaagaatga aatgaatgat 400
< 210 > 326 < 211 > 1215 < 212 > DNA < 213 > Homo sapien < 400 > 326 ggaggactgc agcccgcact cgcagccctg gcaggcggca ctggtcatgg aaaacgaatt 6C gttctgctcg ggcgtcctgg tgcatccgca gtgggtgctg tcagccgcac actgtttcca 12C gaectcctac accatcgggc tgggcctgca cagtcttgag gccgaccaag agccagggag 18C ccagatgctg gaggccagcc tctccgtacg gcacccagag tacaacagac ccttgctcgc 240 atgctcatca taacgacctc agttggacga atccgtgtcc gagtctgaca ccatccggag 300 catcagcatt gcttcgcagt gccctaccgc ggggaactct tgcctcgttt ctggctgggg 360 tctgctggcg aacggcagaa tgcctaccgt gctgcagtgc gtgaacgtgt cggtggtgtc 420 tgaggaggtc tgcagtaagc tctatgaccc gctgtaccac cccagcatgt tctgcgccgg 480 cggagggcaa gaccagaagg actcctgcaa cggtgactct ggggggcccc tgatctgcaa 540 cgggtacttg cagggccttg tgtctttcgg aaaagccccg tgtggccaag ttggcgtgcc 600 aggtgtctac accaacctct gcaaattcac tgagtggata gagaaaaccg tccaggccag 660 ttaactct g ggactgggaa cccatgaaat tgacccccaa atacatcctg cggaaggaat 720 tcaggaatat ctgttcccag cccctcctcc ctcaggccca ggagtccagg cccccagccc 780 ctcctccctc aaaccaaggg tacagatccc cagcccctcc tccctcagac ccaggagtcc 840 agacccccca gcccctcctc cctcagaccc aggagtccag cccctcctcc ctcagaccca 900 ggagtccaga ccccccagcc cctcctccct cagacccagg ggtccaggcc cccaacccct 960 cctccctcag actcagaggt ccaagccccc aacccctcct tccccagacc cagaggtcca 1020 ggtcccagcc cctcctccct cagacccagc ggtccaatgc cacctagact ctccctgtac 1080 acagtgcccc cttgtggcac gttgacccaa ccttaccagt tggtttttca ttttttgtcc gatccagaaa 1140 aaaaaaaaaa aaaaaaaaaa ctttccccta taaagtctaa gagaagcgca aaaaaaaaaa aaaaa 1200 1215 <; 210 > 327 < 211 > 220 < 212 > PRT < 213 > Homo sapien < 400 > 327 Glu Asp Cys Ser Pro His Ser Gln Pro Trp Gln Ala Ala Leu Val Met 1 5 10 15 Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gln Trp Val 20 25 30 Leu Ser "Ala Ala His Cys Phe Gln Asn Ser Tyr Thr lie Gly Leu Gly 35 40 45 Leu His Ser Leu Glu AlaAsp Gln Glu Pro Gly Ser Gln Met Val Glu 50 55 60 Wing Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro Leu Leu Wing 65 70 75 80 F
Asn Asp Leu Met Leu lie Lys Leu Asp Glu Ser Val Ser Glu Ser Asp 85 90 95 Thr lie Arg Ser He Ser Wing Be Gln Cys Pro Thr Wing Gly Asn 100 105 110 Ser Cys Leu Val Ser GlyTrp Gly Leu Leu Wing Asn Gly Arg Met Pro 115 120 125 Thr Val Leu Gln Cys ValAsn Val Ser Val Val Ser Glu Val Val Cys 130 135 140 Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Ser Met Phe Cys Ala Gly 145 150 155 160 Gly Gly Gln Asp Gln Lys Asp Ser Cys Asn Gly Asp Ser Gly Gly Pro 165 170 175 Leu He Cys Asn Gly Tyr Leu Gln Gly Leu Val Ser Phe Gly Lys Wing 18C 185 190 Pro Cys Gly Gln Val GlyVal Pro Gly Val Tyr Thr Asn Leu Cys Lys 195 200 205 Phe Thr Glu Trp He GluLys Thr Val Gln Wing Ser 210 215 220 < 210 > 328 < 211 > 234 < 212 > DNA < 2 13 > : - omo s api in < 400 > ? 28 c ctcgtctc tggtagctgc agccaaatca ggactgca taaacggcga c ccgcactcgc 60 agccctggca ggcggcactg gtcatggaaa acgaattgtt ctgctcgggc gtcctggtgc 120 atccgcagtg ggtgctgtca gccacacact gtttccagaa ctcctacacc atcgggctgg 180 gcctgcacag tcttgaggcc gaccaagagc cagggagcca gatggtggag GCCA 234 < 210 > 329 < 211 > 77 < 212 > PRT < 213 > Homo sapien < 400 > 329 Leu Val Ser Gly Ser Cys Ser Gln He He Asn Gly Glu Aso Cys Ser 1. "5 10 15 Pro His Ser GIr. Pro TrpGln Ala Ala Leu Val Met Glu Asn Glu Leu 20 25 30 Phe Cys Ser Glv Val LeuVal His Pro Gln Trp Val Leu Ser Aia Thr F 35" 40 45 His Cys Phe Gln Asn SerTyr Thr He Gly Leu Gly Leu His Ser Leu 50 55 60 Glu Wing Asp Glr. Glu Pro Gly Ser Gln Met Val Glu Wing 65 70 75 < 210 > 330 < 211 > 70 < 212 > DNA < 213 > Homo sapien < 400 > 330 cccaacacaa tgccccgatc ccatccctga ctccgccctc aggatcgctc stctctggta 60 gctgcagcca 70 < 210 > 331 < 211 > 22 < 212 > PRT F < 213 > Homo sapien < 400 > 331 Gln Hi s Asn Gl and Pro He Pro Ser Leu Thr Pro Pro Ser Gly Ser Leu 1 5 10 15 Val Ser Gly Ser Cys Ser 20 < 210 > 332 < 211 > 2507 < 212 > DNA < 213 > Homo sapien < 400 > 332 tggtgccgct gcagccggca gagatggttg agctcatgtt cccgctgttg ctcctccttc 60 tgcccttcct tctgtatatg gctgcgcccc aaatcaggaa aatgctgtcc agtggggtgt 120 gtacatcaac tgttcagctt cctgggaaag tagttgtggt cacaggagct aatacaggta 180 tcgggaagga gacagccaaa gagctggctcagagaggagc tcgagtatat ttagcttgcc 240 aaagggggaa gggatgtgga ttggtggcca aagagatcca gaccacgaca gggaaccagc 300 aggtgttggt gcgsaaactg gacctgtctgatactaagtc tattcgagct tttgctaagg 360 gcttcttagc tga gaaaag cacctccacg ttttgatcaa caatgcagga gtgatgatgt 420 gtccgtactc gaagatagca gatggctttg agatgcacat aggagtcaac cacttgggtc 480 acttcctcct aacccatctg ctgctagaga aactaaagga atcagcccca tcaaggatag 540 ttcccttgca taaatgtgtc catcacctgg gaaggatcca cttccataac ctgcagsccg 600 agaaattcta caatgcaggc ctggcctact gtcacagcaa gctagccaac atcctct ca 660 cccaggaact ggcccggaga ctaaaaggct ctggcgttac gacgtattct gtacaccctg 720 gcacagtcca atctgaactg gttcggcact catctttcat gagatggatg tggtggcttt 780 tctccttttt catcaa act cctcagcagg gagcccagac cagcctgcac tgtgccttaa 840 cagaaggtct tgagatt cta agtgggaatc atttcagtga ctgtcatgtg gcatgggtct 900 ctgcccaagc tcgtaatgag actatagcaa ggcggctgtg ggacgtcagt tgtgacctgc 960 tgggcctccc aatagactaa caggcagtgc cagttggacc caagagaaga ctgcagcaga 1020 cttcttgtca ctacacagta aaatgattct ccttcaaggt tttcaaaacc tttagcacaa 1080 agagagcaaa accttccagc cttgcctgct tggtatccag ttaaaactca gtgtactgcc 1140 agattcgtct aaatgtctgt catgtccaga tttactttgc ttctgttact gccagagtta 1200 ctagagatat cataatagga taagaagacc ctcatatgac ctgcacagct cattttcctt 1260 ctactaccta ctgaaagaaa agctatagca ggagaatcta gggatgattt atgcaaattt 1320 gaactagctt ctttgttcac aattcagttc ctcccaacca accagtcttc acttcaagag 1380 ggccacactg caacctcagc ttaacatgaa taacaaagac tggctcagga gcagggcttg 1440 cccaggcatg gtggatcacc ggaggtcagt agttcaagac cagcctggcc aacatggtga 1500 aaccccacct ctactaaaaa ttgtgtatat ctttatgtgt cttcctgttt atgtgtgcca 1560 agggagtatt ttcacaaagt tcaaaacagc cacaataatc agagatggag caaaccastg 1620 F ccatccagtc tttatgcaaa tgaaatgctg caaagggaag cagattctgt atatgttggt 1680 caagagcaca aactacccac tg ggtagcag ggaagaagta aaaaaagaga aggagaatac 1740 tggaagataa tgcacaaaat gaagggacta gttaaggatt aactagccct ttaaggatta 1800 actagttaag gattaatagc aaaagayatt aaatatgcta acatagctat ggaggaattg 1860 agggcaagca cccaggactg atgaggtctt aacaaaaacc agtgtggcaa aaaaaaaaaa 1920 aaaaatccta aaaaaaaaaa aaaacaaaca aacaaaaaaa attcagaaaa acaattcttc 1980 attatcttag ggactgatat tggtaattat ggtcaattta ataatatttt ggggcatttc 2040 cttacattgt cttgacaaga ttaaaatgtc tgtgccaaaa ttttgtattt tatttggaga 2100 aaagtaatgc cttcttatca tgccaaagga agtctaagga attagtagtg ttcccatcac 2160 ttgtttqgag tgtgctattc taaaagattt tgatttcctg gaatgacaat tatattttaa 2220 ctttggtggg ggaaagagtt ataggaccac agtcttcact tctgatactt gtaaattaat 2280 cttttattgc acttgttttg accattaagc tatatgttta ttttacggaa gaaatggtca 2340 aattctgata aaattagaaa atagtgcaga ataaatgaat taatgtttta cttaatttat 2400 attgaactgt caatgacaaa taaaaattct ttttgattat tttttgtttt catttaccag 2460 aataaaaacg taagaattaa aagtttgatt acaaaaaaaa 2507 <aaaaaaa; 210 > 333 < 211 > 3030 < 212 > DNA F
< 213 > Homo sapien < 400 > 333 gcaggcgact tgcgagctgg gagcgattta aaacgctttg gattcccccg gcctgggtgg 60 ggagagcgag ctgggtgccc cctagattcc ccgcccccgc acctcatgag ccgaccctcg 120 gctccatgga gcccggcaat tatgccacct tggatggagc caaggatatc gaaggcttgc 180 tgggagcggg aggggggcgg aatctggtcg cccactcccc tctgaccagc cacccagcgg 240 cgcctacgct gatgcctgct gtcaactatgcccccttgga tctgccaggc tcggcggagc 300 atgccaccca cgccaaagca tgccctgggg tgccccaggg gacgtcccca gctcccgtgc 360 cttatggtta ctttggaggc gggtactact cctgccgagt gtcccggagc tcgctgaaac 420 cctgtgccca ggcagccacc ctggccgcgt accccgcgga gactcccacg gccggggaag 480 agtaccccag ycgccccact gagtttgcct tctatccggg atatccggga acctaccagc 540 ctatggccag ttacctggac gtgtctgtgg tgcagactct gggtgctcct ggagaaccgc 600 gacatgactc cctgttgcct gtggacagtt accagtcttg ggctctcgct ggtggctgga 660 ^ _ acagccagat gtgttgccag ggagaacaga acccaccagg tcccttttgg aaggcagcat 720, ^ B ttgcagactc cagcgggcag caccctcctgacgcctgcgc ctttcgtcgc ggccgcaaga 780 ^^ aacgcattcc gtacagcaag gggcagttgcgggagctgga gcgggagtat gcggctaaca 840 agttcatcac caaggacaag aggcgcaaga tctcggcagc caccagcctc tcggagcgcc 900 agattaccat ctggtttcag aaccgccggg tcaaagagaa gaaggttctc gccaaggtga 960 agaacagcgc taccccttaa gagatctcct tgcctgggtg ggaggagcga aagtgggggt 1020 gtcctgggga gaccaggaac ctgccaagcc caggctgggg ccaaggactc tgctgagagg 1080 cccctagaga caacaccctt cccaggccac tggctgctgg actgttcctc aggagcggcc 1140 tgggtaccca gtatgtgcag ggagacggaa ccccatgtga cagcccactc caccagggtt 1200 cccaaagaac ..ecc-c .- cataatcattcatcctgaca gtggcaataa teaegataac 1260 cagtactagc gttagcctcatattttctat etagagetet gtanagcact 1320 ttagaaaccg ct ttcstgaa ttgagctaat tatgaataaa tttggaaggc gatccctttg cag 1380 gaagct tt: c:; aca cccccttcca caccctggta ttacacctct acageage and 1- - 0 gactgaggag ac cggaacgg gcagattcgt tgtgtggctg tgatgtccgt ttagcatttt ca 1300 tctcagctga ctgggta ggtggacaat tgtagaggct gtctcttcct ccctccttgt 1560 ccaccccata actggtcttggaagcaccca teettaatac gatgattttt 1620 ctgtcgtgtg aa aatgaagc cagcaggctg cccctagtca gtccttcctt ccagagaaaa 1680 agagatttga ga aagtgcct gggtaat ea cca ttaattt cctcccccaa actctctgag 1740 tcttccctta at atttctgg tggttctgaccaaagcaggt catggtttgt tgagcatttg 1800 ggatcccagt ga agtagatg tttgtagcct tgeataetta gcccttccca ggcacaaacg 1S60 gagtggcaga gt cgtgccaa ccccgttttcccagtccacg tagacagatt cacagtgcgg 1920 getggagaca aattctggaa ttgeagagee gacgggctct gggactctga gagggacatg 1980 agggcctctg cetctgtgtt cattctctga tgtcctgtac ctgggctcag tgcccggtgg 2040 gactcatctc ct ggccgcgc agcaaagccagcgggttcgt gctggtcctt ectgcacct 2100 aggctggggg tg ggg SCCT gccggcgcat tctccacgat tgagcgcaca ggcctgaagt 2160 ctggacaacc CC tagaaccg aagctccgagcagcgggtcg gtggcgagta gtggggtcgg 2220 tggcgagcag tt egtggtgg gccgcggccgccactacete gaggacattt ccctcccgga 2280 gccagctctc ct agaaaece cgcggcggccgccgcagcca agtgtttatg gcccgcggtc 2340 gggtgggatc ct agccctgt ctcctctcct gggaaggaat gagggtggga cgtgacttag 2400 acacctacaa at ttatttac caaagaggag cccgggactg agggaaaagg ccaaagagtg 2460 f tgagtgcatg ce actgggg gttcagggga agaggacgag gaagaggaag atgaggtcga 2520 tttcctgatt ta aaaaa cg tccaagcccc gtg gtccagc ttaaggtcct cggttacatg 2580 cgccgctcag ac taggtcac tttctgccttccacgtcctc cttcaaggaa gccccatgtg 2640 ggtagctttc aa tategeag gttcttactcctctgcctct ataagetcaa acccaccaac 2 ~ O0 gatcgggcaa aaaccccc tccctcgccg acttcggaac tggcgagagt teagegeaga 2 ~ 60 tgggcctgtg ge agggggc aagatagatgagggggagcg gcatggtgcg gggtgacccc 2820 ttggagagag ga aaaaggcc acaagaggggctgccaccgc cactaacgga gatggccctg 2880 gtagagacct tt gggggtct ggaacctctggactccccat gctctaactc ccacactctg 2940 ctatcagaaa cttaaacttg aggattttct ctgtttttca ctcgcaataa aytcagagca 3000 aacaaaaaaa aaaaaaaaaa aaaactcgag 3030 < 210 > 334 < 211 > 2417 < 212 > DNA < 213 > Homo sapien < 400 > 334 gaattcggca ggcggccgct ctagagctag tgggatcccc cgggctgcac cgagtgagtt 60 ggagttttac ctgtattgtt ttaatttcaa caagcctgag gactagccac aaatgtaccc 120 F agtttacaaa tcaggaaaca ggtgcaaaaa ggttgttacc tgtcaaaggt cgtatgtggc 180 agagecaaga tttgagccca gttatgtctg atgaacttag cctatgctct ttaaacttct 240 gaatgctgac cattgaggat atctaaactt agatcaattg cattttccct ccaagactat 300 ttaettatca atacaataat accaccttta ecaatetatt gttttgatac gagaetcaaa 360 tatgecagat atatgtaaaa gcaacctacaagctctctaa tcatgctcac ctaaaagatt 420 aataggctca cccgggatct aagaaacttc tctagaaat ataaaagaga aaattggatt 480 atgcaaaaat tcattattaa tttttttcat ccatccttta attcagcaaa catttatctg 540 ttgttgactt tatgeagtat ggccttttaa ggattggggg acaggtgaag aacggggtgc 600 cagaatgeat cctcctacta atgaggtcag tacacatttg cattttaaaa tgccctgtcc 660 agctgggcat ggtggatcat gcctgtaatc tcaacattgg aaggccaagg caggaggatt 720 gcttcagccc acgagttcaa gaccagcctgggcaacatag aaagacccca tctctcaatc 780 tgccctgtct aatcaatcaa aactctttaa ttgaaaataa gaaaggttta atgggcaggg 840 tgtggtagct catgectata atacageact ttgggaggct gaggcaggag gatcaettta 900 gcccagaagt tcaagaccag cctgggcaacaagtgacacc teatetcaat tttttaataa 960 tacataagga aatgaataca aagataaaaagaaaagttta atgaaagaat acagtataaa 1020 acaaatctct t sacctaaa agtatttttg ttcaagecaa atattgtgaa tcacctctct 1080 gtgttgagga tacagaatat ctaagcccaggaaactgagc agaaagttca tg tactaact 1140 acgcaaggca aatcaacccg taactaatca aaaatgagac atccgaggca aggggcaaat 1200 tagacggaac ctgactctgg tetattaage gacaaettte cctctgttgt atttttcttt 1260 aaaaggataa tattcaatgt aaactaaaaa aaacteteta caatgtttgt caggagttac 1320 caactaatta aaaccatgac tggggaatca taaaatatga ctgtatgaga tcttgatggt 1380 ttacaaagtg tacccactgt taatcacttt aaacattaat gaacttaaaa atgaatttac 1440 ggagattgga atgtttcttt cctgttgtat tagttggctc aggctgccat aacaaaatac 1500 cacagactgg gaggcttaag taacagaaat tcatttctca cagttct gg ggctggaagt 1560 cgtgcagsaa ccacgatcaa aggcaggct cattctgagg cccctctctt ggctcacats 1620 tggccaccct ctcactscgt gctcacatga cctctttgtg ctcctgsaaa gagggtgtgg 1680 gggacagagg gaaagagaag gagagggaac tctctggtgt ctcgtctttc aaggacccta 1740 ctttggccca acctgggcca ggcactgtggggtggggggt tgtggctgct ctgctct ag 1800 tggccaaaat aaagcaacag aaaaatgtcc aaagctgtgc agcaaagaca agccaccgaa 1860 cagggatctg ctcatcagtg tggggacctc caagtcggcc accctcaagg caagccccca 1920 cagagcccat ccaaggtggc agcagcagaa gaagggaatt gtccctgtcc ttggcacatt 1980 cctcaccgac ctggtgatgc tggacactgcgatgaatggt aatgtggatg agaatatoat 2040 ggactcccag aaaaggagac ccagctgctc aggtggctgc aaatcattac agccttcatc 2100 ctggggagga actgggggcc tggttctggg tcagagagca gcccagtgag ggtgagagct 2160 acagcctgtc ctgccagctg gatccccagt cccggtcaac cagtaatcaa ggctgagcag 2220 atcaggcttc ccggagctgg tcttgggaag ccagccctgg ggtgagttgg ctcctgctgt 2280 ggtactgaga caatattgtc ataaattcaa tgcgcccttg tatccctttt tcttttttat 2340 ctgtctacat ctataatcac tatgcatact agtctttgtt agtgtttcta ttcmacttaa 2400 tagagatatg ttatact 2417
< 210 > 335 < 211 > 2984 < 212 > DNA < 213 > Homo sapien < 400 > 335 atccctcctt ccccactctc ctttccagaa ggcacttggg gtcttatctg ttggactctg 60 aaaacacttc aggcgccctt ccaaggcttc cccaaacccc taagcagccg cagaagcgct 120 cccgagctgc cttctcccac actcaggtga tcgagttgga gaggaagttc agccatcaga 180 agtacctgtc ggcccctgaa cgggcccacc tggccaagaa cctcaagctc acggagaccc 240 aagtgaagat atggttccag aacagacgct ataagactaa gcgaaagcag ctctcctcgg 300 agctgggaga cttggagaag cactcctctt tgccggccct gaaagaggag gccttctccc 360 gggcctccct ggtctccgtg tataacagct atccttacta cccatacctg tactgcgtgg 420 gcagctggag cccagctttt tggtaatgccagctcaggtg acaaccatta tgatcaaaaa 480 ctgccttccc cagggtgtct CtatgaaaagCacaaggggc caaggtcagg gagcaagagg 540 tgtgcacacc aaagctattg gagatttgcg tggaaatctc asattcttca ctggtgagac 600 aatgaaacaa cagagacagt gaaagtttta atacctaagt cattccccca gtgcatactg 660 taggtcattt tttttgcttc tggctacctg tttgaagggg agagagggaa aatcaagtgg 720 tattttccag cactttgtat gattttggat gagctgtaca ctgttctgca cccaaggatt 780 actccatcct cctgtgtcac tgaatatcaa gcaaacctaa ctctgaaaga caggagaaag 840 gacaaccagg atgaggat gt caccaactga attaaactta agtccagaag cctcctgttg 900 gccttggaat atggccaagg ctctctctgt ccctgtaaaa gagaggggca aatagagagt 960 ctccaagaga acgccctcat gctcagcaca tatttgcatg ggagggggag atgggtggga 1020 ggagatgaaa atatcagctt ttcttattcc tttttattcc ttttaaaatg gtatgccaac 1080 ttaagtattt acagggtggc ccaaatagaacaagatgcac tcgctgtgat tttaagacaa 1140 cagaactcca gctgtataaa ctgcaagagggggggccggg ccaggagaat ctccgcttgt 1200 gccctaagga ccaagacagg gggtctccacactgctgcta ggggctgttg cattttttta 1260 ttagtagaaa gtggaaaggc ctcttctcaa cttttttccc ttgggctgga gaatttagaa 1320 tcagaagttt cctggagttt tcaggctatc atatatactg tatcctgaaa ggcaacataa 1380 ttcttccttc cctcctttta aaattttgtg ttcctttttg cagcaattac tcactaaagg 1440 gcttcatttt agtccagatt tttagtctgg ctgcacctaa cttatgcctc gcttatttag 1500 cccgagatct ggtctttttt tttttttttt tttttccgtc tccccaaagc tttatctgtc 1560 ttgacttttt aaaaaagttt gggggcagat tctgaattgg tgcattttta ctaaaagaca 1620 aaactagcaa ctcttatttc tttcctttaa aaatacatag cattaaatcc caaatcctat 1680 gacagcttga ttaaagacct gaaggtca ct actgcattta taggaccttc tggtggttct 1740 gctgttacgt ttgaagtctg acaatccttgagaatctttg catgcagagg aggtaagagg 1800 tattggattt tcacagagga agaacacagc gcagaatgaa gggccaggct tactgagctg 1860 tccagtggag ggctcatggg tgggacatgg aaaagaaggc agcctaggcc ctggggagcc 1920 cagtccactg agcaagcaag ggactgagtgagccttttgc aggaaaaggc taagaaaaag 1980 ctaaaacaca gaaaaccatt acaagaaact gtccaaatgc tttaggaact gtgtttattg 2040 cctataatgg gtccccaaaa taggtaacct agacttcaga gagaatgagc agagagcaaa 2100 ggagaaatct ggctgtcctt ccattttcat tctgttatct caggtgagct ggtagagggg 2160 aaaaaatgaa agacattaga acaacaaaac aattactaat gaggtacgct gaggcctggg 2220 agtctcttga ctccactact taattccgtn tagtgagaaa cctttcaatt ttcttttatt 2280 agaagggcca gcttactgtt ggtggcaaaa ttgccaacat aagttaatag aaagttggcc 2340 aatttcaccc cattttctgt ggtttgggct ccacattgca atgttcaatg ccacatgctg 2400 ctgacaccga ccggagtact agccagcacaaaaggcaggg tagcctgaat cgctttctgc 2460 tctttacatt tcttttaaaa taagcatttagtgctcagtc cctactgagt actctttctc 2520 tcccctcctc tgaatttaat tctttcaact tgcaat TTGC aaggattaca catttcactg 2580 aaaaaaaaaa tgatgtatat tgtgttgcaa aagtgtcttt gtttaaaatt acttggtttg 2640 tgaatccatc ttgctttttc cccattggaactagtcatta acccatctct gaactggtag 2700 aaaaacatct gaagagctag tctatcagca tctgacaggt gaattggatg gttctcagaa 2760 ccatttcacc cagacagcct gtttctatcctgtttaataa attagtttgg gttctctaca 2820 tgcataacaa accctgctcc aatctqtcacataaaagtct gtgacttgaa gtttagtcag 2880 cacccccacc aaactttatt tttctatgtg ttttttgcaa catatgagtg ttttgaaaat 2940 aaaaaaaaaa aaaa tgtctttatt aaagtaccca agaaaaaaaa 2984
< 210 > 336 < 211 > 147 < 212 > PRT < 213 > Homo sapien < 400 > 336 Pro Ser Phe Pro Thr Leu Leu Ser Arg Arg His Leu Gly Ser Tyr Leu 1 5 10 15 Leu Asp Ser Glu Asn Thr Ser Gly Ala Leu Pro Arg Leu Pro Gln Thr 20 25 30 Pro Lys Gln Pro Gln Lys Arg Ser Arg Ala Wing Phe Ser His Thr Gln 35 40 45 Val He Glu Leu Glu Arg Lys Phe Ser His Gln Lys Tvr Leu Ser Wing 50 55 60 Pro Glu Arg Ala His LeuAla Lys Asn Leu Lys Leu Thr Glu Thr Gln 65 70 75 80 Val Lys He Trp Phe Gln Asn Arg Arg Tyr Lys Thr Lys Arg Lys Gln 85 90 95 Leu Ser Ser Glu Leu Gly Asp Leu Glu Lys His Ser Ser Leu Pro Ala 100 105 110 Leu Lys Glu Glu Ala Phe Ser Arg Ala Ser Leu Val Ser Val Tyr Asn 115 120 125 Ser Tyr Pro Tyr Tyr Pro Tyr Leu Tyr Cys Val Gly Ser Trp Ser Pro 130 135 140 Wing Phe Trp 145 <; 210 > 337 < 211 > 9 < 212 > PRT < 213 > Homo sapien < 400 > 337 Wing Leu Thr Gly Phe Thr Phe Being Wing
< 210 > 338 < 211 > 9 < 212 > PRT < 213 > Homo sapien < 400 > 338 Leu Leu Ala Asn Asp Leu Met Leu He 1 5 < 210 > 339 < 211 > 318 < 212 > PRT < 213 > Homo sapien < 400 > 339 Met Val Glu Leu Met Phe Pro Leu Leu Leu Leu Leu Leu Pro Phe Leu 1 5 10 15 Leu Tyr Met Ala Wing ProGln He Arg Lys Met Leu Ser Ser Gly Val 20 25 30 Cys Thr Ser Thr Val GlnLeu Pro Gly Lys Val Val Val Val Thr Gly 35 40 45 Wing Asn Thr Gly He Gly Lys Glu Thr Wing Lys Glu Leu Wing Gln Arg 50 55 60 Gly Wing Arg Val Tyr LeuAla Cys Arg Asp Val Glu Lys Gly Glu Leu 65 70 75 80 Val Ala Lys Glu He GlnThr Thr Thr Gly Asn Gln Gln Val Leu Val 85 90 95 Arg Lys Leu Asp Leu SerAsp Thr Lys Ser He Arg Wing Phe Wing Lys 100 105 110 Gly Phe Leu Wing Glu Glu Lys His Leu His Val Leu He Asn Asn Wing 115 120 125 Gly Val Met Met Cys Pro Tyr Ser Lys Thr Wing Asp Gly Phe Glu Met 130 135 140 His He Gly Val Asn His Leu Gly His Phe Leu Leu Thr His Leu Leu 145 150 155 160 Leu Glu Lys Leu Lys Glu Ser Ala Pro Ser Arg He Val Asn Val Ser 165 170 175 Ser Leu Ala His His Leu Gly Arg He His Phe His Asn Leu Gln Gly 180 185 190 Glu Lys Phe Tyr Asn Wing Gly Leu Wing Tyr Cys His Ser Lys Leu Wing 195 200 205 Asn He Leu Phe Thr Gln Glu Leu Wing Arg Arg Leu Lys Gly Ser Gly 210 215 220 Val Thr Thr Tyr Ser Val His Pro Gly Thr Val Gln Ser Glu Leu Val 225 230 235 240 Arg His Ser Ser Phe Met Arg Trp Met Trp Trp Leu Phe Ser Phe Phe 245 250 255 He Lys Thr Pro Gln Gln Gly Wing Gln Thr Ser Leu His Cys Ala Leu 260 265 270 Thr Glu Gly Leu Glu He Leu Ser Gly Asn His Phe Ser Asp Cys His 275 280 285 Val Wing Trp Val Ser Wing Gln Wing Arg Asn Glu Thr He Wing Arg Arg 290 295 300 Leu Trp Asp Val Ser Cys Asp Leu Leu Gly Leu Pro He Asp 305 310 315 < 210 > 340 < 211 > 483 < 212 > DNA < 213 > Homo sapien < 400 > 340 gccgaggtct gccttcacac ggaggacacg agactgcttc ctcaagggct cctgcctgcc 60 tggacactgg tgggaggcgc tgtttagttggctgttttca gaggggtctt tcggagggac 120 ctcctgctgc aggctggagt gtctttattcctggcgggag accgcacatt ccactgctga 180 ggttgtgggg gcggtttatc aggcagtgat aaacataaga tgtcatttcc ttgactccgg 240 ccttcaattt tctctttggc tgacgacggagtccgtggtg tcccgatgta actgacccct 300 gctccaaacg tgacatcact gatgctcttc tcgggggtgc tgatggcccg cttggtcacg 360 tgctcaatct cgccattcga ctcttactcc aaactgtatg aagacacctg actgcacgtt 420 ttttctaggc ttccagaatt taaagtgaaa ggcagcactc ctaagctccg actccgatgc 480 ctg 483
< 210 > 341 < 211 > 344 < 212 > DNA < 213 > Homo sapien < 400 > 341 ctgctgctga gtcacagatt tcattataaa tagcctccct aaggaaaata cactgaatgc 60 tatttttact aaccattcta tttttataga aatagctgag agtttctaaa ccaactctct 120 gctgccttac aagtattaaa tattttactt ctttccataa agagtagctc aaaatatgca 180 attaatttaa taatttctga tgatggtttt atctgcagta atatgtatat catctattag 240 aatttactta atgaaaaact gaagagaacaaaatttgtaa ccactagcac ttaagtactc 300 ACAG 344 ctgattctta acattgtctt taatgaccacaagacaacca
< 210 > 342 < 211 > 592 < 212 > DNA < 213 > Homo sapien < 400 > 342 acagcaaaaa agaaactgag aagcccaaty tgctttcttg ttaacatcca cttatccaac 60 acttcttata caatgtggaa ttatgaagtt cttggttcca tgctatcaca ggacaattgc 120 cctggcaggt aaaccaatgc caagagagtgatggaaacca ttggcaagac tttgttgatg 180 accaggattg gaattttata aaaatattgt tgatgggaag ttgctaaagg gtgaattact 240 tccctcagaa gagtgtaaag aaaagtcagagatgctataa tagcagctat tttaattggc 300 aagtgccact gtggaaagag ttcctgtgtg tgctgaagtt gtcaaattca ctgaagggca 360 tcagcatggg ctgtttggtg caaatgcaaaagcacaggtc tttttagcat gctggtctct 420 cccgtgtcct tatgcaaata atcgtcttct tctaaatttc tcctaggctt cattttccaa 480 agttcttctt ggtttgtgat gtcttttctgctttccatta attctataaa atagtatggc 540 ttcagccacc cactcttcgc cttagcttgaccgtgagtct cggctgccgc tg 592 < 210 > 343 < 211 > 382 < 212 > DNA < 213 > Homo sapien < 400 > 343 ttcttgacct cctcctcctt caagctcaaacaccacctcc cttattcagg accggcactt 60 cttaatgttt gtggctttct ctccagcctc tcttaggagg ggtaatggtg gagttggcat 120 cttgcaactc tcctttctcc tttcttcccc tttctctgcc cgcctttccc atcctgctgt 180 agacttcttg attgtcagtc tgtgtcacat ccagtgattg ttttggtttc tgttcccttt 240 ctgactgccc aaggggctca gaaccccagc aatcccttcc tttcactacc ttcttttttg 300 ggggtagttg gaagggactg aaattgtggggggaaggtaq aaggcacatc aataaagagg 360 aa 382 gctgaaaaaa aaaccaccaa
< 210 > 344 < 211 > 536 < 212 > DNA < 213 > Homo sapien < 400 > 344 ctgggcctga agctgtaggg taaatcagaggcaggcttct gagtgatgag agtcctgaga 60 cataaactta caataggcca gctggatggaacctcacaat aaggtggtca cctcttgttt 120 gtttaggggg atgccaagga taaggccagc tcagttatat gaagagaagc agaacaaaca 180 agtctttcag agaaatggat gcaatcagag tgggatcccg gtcacatcaa ggtcacactc 240 caccttcatg tgcctgaatg gttgccaggt cagaaaaatc caccccttac gagtgcggct 300 tcgaccctat atcccccgcc cgcgtccctt tctccataaa attcttctta gtagctatta 360 atttgatcta ccttcttatt gaaattgccc tccttttacc cctaccatga gccctacaaa 420 gccactaata caactaacct gttatgtcat ccctcttatt aatcatcatc ctagccctaa 480 gtctggccta tgagtgacta caaaaaggat tagactgagc cgaataacaa aaaaaa 536 < 210 > 345 < 211 > 251 < 212 > DNA < 213 > Homo sapien < 400 > 345 accttttgag gtctctctca ccacctccac agccaccgtc accgtgggat gtgctggatg 60 tgaatgaagc ccccatcttt gtgcctcctg aaaagagagt ggaagtgtcc gaggactttg 120 ggaaatcaca gcgtgggcca tcctacactg cccaggagcc agacacattt atggaacaga 180 aaataacata tcggatttgg agagacactg ccaactggct ggagattaat ccggacactg gtgccatttc c 251 240
< 210 > 346 < 211 > 282 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse characteristic < 222 > ( 1 ) . . . (282) < 223 > n = A, T, C or G < 400 > 346 cgcgtctctg acactgtgat catgacaggg gttcaaacag aaagtgcctg ggccctcctt 60 ctaagtcttg ttaccaaaaa aaggaaaaag aaaagatctt ctcagttaca aattctggga 120 agggagacta tacctggctc ttgccctaag tgagaggtct tccctcccgc accaaaaaat 180 agaaaggctt tctatttcac tggcccaggt agggggaagg agagtaactt tgagtctgtg 240 ggtctcattt cccaaggtgc cttcaatgct catnaaaacc aa 282 < 210 > 347 < 211 > 201 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (201) < 223 > n = A, T, C or < 400 > 347 acacacataa tattataaaa tgccatctaa ttggaaggag ctttctatca ttgcaagtca 60 taaatataac ttttaaaana ntactancag cttttaccta ngctcctaaa tgcttgtaaa 120 tctgagactg actggaccca cccagaccca gggcaaagat acatgttacc atatcatctt 180 tataaagaat ttttttttgt c 201
< 210 > 348 < 211 > 251 < 212 > DNA < 213 > Homo sapien < 400 > 348 ctgttaatca caacatttgt gcatcacttg tgccaagtga gaaaatgttc taaaatcaca 60 agagagaaca gtgccagaat gaaactgacc ctaagtccca ggtgcccctg ggcaggcaga 120 aggagacact cccagcatgg aggagggttt atcttttcat cctaggtcag gtctacaatg 180 ggggaaggtt ttattataga actcccaaca gcccacctca ctcctgccac ccacccgatg gccctgcctc c 251 240
< 210 > 349 < 211 > 251 < 212 > DNA < 213 > Homo sapien < 400 > 349 taaaaatcaa gccatttaat tgtatctttg aaggtaaaca atatatggga gctggatcac 60 aacccctgag gatgccagag ctatgggtcc agaacatggt gtggtattat caacagagtt 120 cagaagggtc tgaactctac gtgttaccag agaacataat gcaattcatg cattccactt 180 agcaattttg taaaatacca gaaacagacc ccaagagtct ggaaaattca ttcaagatga actcctggtt 240 t 251 < 210 > 350 < 211 > 908 < 212 > DNA < 213 > Homo sapien < 400 > 350 ctggacactt tgcgagggct tttgctggct gctgctgctg cccgtcatgc tactcatcgt 60 agcccgcccg gtgaagctcg ctgctttccc tacctcctta agtgactgcc aaacgcccac 120 cggctggaat tgctctggtt atgatgacagagaaaatgat ctcttcctct gtgacaccaa 180 cacctgtaaa tttgatgggg aatgtttaag aattggagac actgtgactt gcgtctgtca 240 gttcaagtgc aacaatgact atgtgcctgt gtgtggctcc gctaccagaa aatggggaga 300 tgagtgttac ctgcgacagg ctgcatgcaaacagcagagt gagatacttg tggtgtcaga 360 aggatcatgt gccacagtcc atgaaggctc tggagaaact agtcaaaagg agacatccac 420 ctgtgatatt tgccagtttg gtgcagaatg tgacgaagat gccgaggatg tctggtgtgt 480 gtgtaatatt gactgttctc aaaccaactt caatcccctc tgcgcttctg atgggaaatc 540 ttatgataat gcatgccaaa tcaaagaagcatcgtgtcag aaacaggaga aaattgaagt 600 catgtctttg ggtcgatgtc aagataacacaactacaact actaagtctg aagatgggca 660 acagattatg ttatgcaaga cagagaatgc taacaaatta gaagaaagtg ccagagaaca 720 ccacatacct tgtccggaac attacaatgg cttctgcatg catgggaagt gtgagcattc 780 tatcaatatg caggagccat cttgcaggtg tgatgctggt tatactggac aacactgtga 840 aaaaaaggac tacagtgttc tatacgttgt tcccggtcct gtacgatttc agtatgtctt 900 aatcgcag 908
<; 210 > 351 < 211 > 472 < 212 > DNA < 213 > Homo sapien < 400 > 351 ccagttattt gcaagtggta agagcctatt taccataaat aatactaaga accaactcaa 60 gtcaaacctt aatgccattg ttattgtgaa ttaggattaa gtagtaattt tcaaaattca 120 cattaacttg attttaaaat cagwtttgygagtcatttac cacaagctaa atgtgtacac 180 tatgataaaa acaaccattg tattcctgtt tttctaaaca gtcctaattt ctaacactgt 240 atatatcctt cgacatcaat gaactttgtt ttcttttact agtaggcaca ccagtaataa 300 gatctgtcca caacaaactt gccctctcat gccttgcctc tcaccatgct ctgctccagg 360 tcagccccct tttggcctgt ttgttttgtc aaaaacctaa tctgcttctt gcttttcttg 420 gtaatatata tttagggaag atgttgcttt gcccacacac gaagcaaagt aa 472
< 210 > 352 < 211 > 251 < 212 > DNA < 213 > Homo sapien < 400 > 352 atctctcggg ctcaaagcta aatcaaacca gaaaagggca aggatcttag gcatggtgga 60 tgtggataag gccaggtcaa tggctgcaag aagaggtaca catgcagaga tcggagcgtg 120 caggctgcgt tccgtcctta cgatgaagac cacgatgcag tttccaaaca ttgccactac 180 atacatggaa aggaggggga agccaaccca gaaatgggct ttctctaatc ctgggatacc aataagcaca 240 251
< 210 > 353 < 211 > 436 < 212 > DNA < 213 > Homo sapien < 400 > 353 tttttttttt tttttttttt ttttttacaa caatgcagtc atttatttat tgagtatgtg 60 cacattatgg tattattact atactgatta tatttatcat gtgacttcta attaraaaat 120 gtatccaaaa gcaaaacagc agatatacaa aattaaagag gacattaaca acagaagata 180 gataaggcaa cttatacatt gacaatccaa atccaataca tttaaacatt tgggaaatga 240 gggggacaaa tggaagccar atcaaatttg tgtaaaacta ttcagtatgt ttcccttgct 300 tcatgtctga raaggctctc ccttcaatggggatgacaaa ctccaaatgc cacacaaatg 360 actagattca ttaacagaat cactggaacg ggggtaaaga ttctataaaa agaaattatt 420 gggctcctaa tgtagt 436
< 210 > 354 < 211 > 854 < 212 > DNA < 213 > Homo sapien < 400 > 354 ccttttctag ttcaccagtt ttctgcaaggatgctggtta gggagtgtct gcaggaggag 60 caagtctgaa accaaatcta ggaaacataggaaacgagcc aggcacaggg ctggtgggcc 120 atcagggacc accctttggg ttgatatttt gcttaatctg catcttttga gtaagatcat 180 ctggcagtag aagctgttct ccaggtacat ttctctagct catgtacaaa aacatcctga 240 aggactttgt caggtgcctt gctaaaagccagatgcgttc ggcacttcct tggtctgagg 300 ttaattgcac acctacaggc actgggctca tgctt-CAAG tattttgtcc tcactttagg 360 gtgagtgaaa gatccccart ataggagcac ttgggagaga tcatataaaa gctgactctt 420 gagtacatgc agtaatgggg tagatgtgtg tggtgtgtct tcattcctgc aagggtgcct 480 gttagggagt gtttccagga ggaacaagtc tgaaaccaat catgaaataa atggcaggtg 540 aactaattca tgaactggaa cgtgatatca aaagagagat gtgtggttga tacaccttgg 600 caatatggaa ggctctaatt tgcccatatt tgaaataata attcagcttt ttgtaataca 660 ggattgagaa aaataacaaa tcatggtgtc taatgtataa aagacccagg aaacataaat 720 atatcaactg cataaatgta aaatgcatgt gacccaagaa ggccccaaag tggcagacaa 780 cattgtaccc attttccctt ccaaaatgtgagcggcgggc ctgctgcttt caaggctgtc 840 acacgggatg TCAG 854
< 210 > 355 < 211 > 676 < 212 > DNA < 213 > Homo sapien < 400 > 355 gaaattaagt atgagctaaa ttccctgtta aaacctctag gggtgacaga tctcttcaac 60 caggtcaaag ctgatctttc tggaatgtca ccaaccaagg gcctatattt atcaaaagcc 120 atccacaagt catacctgga tgtcagcgaa cagggcacgg aggcagcagc agccactggg 180 gacagcatcg ctgtaaaaag cctaccaatg agagctcagt tcaaggcgaa ccaccccttc 240 ctgttcttta taaggcacac tcataccaacacgatcctat tctgtggcaa gcttgcctct 300 ccctaatcag atggggttga gtaaggctca gagttgcaga tgaggtgcag agacaatcct 360 gtgactttcc cacggccaaa aagctgttcacacetcacqc acctctgtgc ctcagtttgc 420 aataggtcta tcatctgcaa ggatttcttc caaccatttc atgagttgtg aagctaaggc 480 tttgttaatc atggaaaaag gtagacttat gcagaaagcc tttctggctt tcttatctgt 540 ggtgtctcat ttgagtgctg tccagtgaca tgatcaagtc aatgagtaaa attttaaggg 600 attagatttt cttgacttgt atgtatctgt gagatcttga ataagtgacc tgacatctct gcttaaagaa aaccag 660 676 < 210 > 356 < 211 > 574 < 212 > DNA < 213 > Homo sapien < 400 > 356 tttttttttt tttttcagga aaacattctc ttactttatt tgcatctcag caaaggttct 60 catgtggcac ctgactggca tcaaaccaaa gttcgtaggc caacaaagat gggccactca 120 caagcttccc atttgtagat ctcagtgcct atgagtatct gacacctgtt cctctcttca 180 gtctcttagg gaggcttaaa tctgtctcag gtgtgctaag agtgccagcc caaggkggtc 240 aaaagtccac aaaactgcag tctttgctgg gatagtaagc caagcagtgc ctggacagca 300 gagttctttt cttgggcaac agataaccag acaggactct aatcgtgctc ttattcaaca 360 tctgcctaga ttcttctgtc ctggaataaa aagccaatct ctctcgtggc acagggaagg 420 agatacaagc tcgtttacat gtgatagatc taacaaaggc atctaccgaa gtctggtctg 480 gatagacggc acagggagct cttaggtcag cgctgctggt tggaggacat tcctgagtcc 540 agctttgcag cctttgtgca acagtacttt ccca 574
< 210 > 357 < 211 > 393 < 212 > DNA < 213 > Homo sapien < 400 > 357 tttttttttt tttttttttt tttttttttt 60 taatatggkg tacagaatat aratgcttta tcactgkact kcttgttcac tatacttaaa aatgcaccac tcataaatat ttaattcagc 120 aagccacaac caaracttaa ttttatcaac aaaaacccct aaatataaac ggsaaaaaag 180 atagatataa ttattccagt ttttttaaaa cttaaaarat attccattgc cgaattaara 240 araarataag tgttatatgg aaagaagggc attcaagcac actaaaraaa cctgaggkaa 300 gcataatctg tacaaaatta aactgtcctt tttggcattt taacaaattt gcaacgktct 360 tttttttttt tac tttttttctt tttctgtttt 393
< 210 > 358 < 211 > 630 < 212 > DNA < 213 > Homo sapien < 400 > 358 acagggtaaa caggaggatc cttgctctca cggagcttac attctagcag gaggacaata 60 ttaatgttta taggaaaatg atgagtttat gacaaaggaa gtagatagtg ttttacaaga 120 gggaagctaa gcatagagta tccagcacag ggaggtcaca gagacatccc taaggaagtg 180 gagtttaaac tgagagaagc aagtgcttaa actgaaggat gtgttgaaga agaagggaga 240 gtagaacaat ttgggcagag ggaaccttat agaccctaag gtgggaaggt tcaaagaact - 300 gaaagagagc tagaacagct ggagccgttc tccggtgtaa agaggagtca aagagataag 360 attaaagatg tgaagattaa gatcttggtg gcattcaggg attggcactt ctacaagaaa 420 tcactgaagg gagtaatgtg acattacttt tcacttcagg atggccattc taactccagg '480 gggtagactg gactaggtaa gactggaggc aggtagacct cttctaaggc ctgcgatagt 540 gaaagacaaa aataagtggg gaaattcagg ggatagtgaa aatcagtagg acttaatgag 600 caagccagag gttcctccac aacaaccagt 630
< 210 > 359 < 211 > 620 < 212 > DNA < 213 > Homo sapien < 400 > 359 aaaatataca acagcattcc tctagagact aarrgtaaat gctctatagt gaagaagtaa 60 taattaaaaa atgctactaa tatagaaaat ttataatcag aaaaataaat attcagggag 120 ctcaccagaa gaataaagtg ctctgccagt tattaaagga ttactgctgg tgaattaaat 180 atggcattcc ccaagggaaa tagagagatt cttctggatt atgttcaata tttatttcac 240 gttttaggaa aggattaact cagatataaa gcttcgccac ggaagagatg gacaaagcac 300 tgatacctta aaagacaaca ggaagcaaca ctaccctttc aggcataaaa tttggagaaa 360 tgcttcatga tgcaacatta ataatatgta gaaagaaggt ctgatgaaaa tgacatcctt 420 aatgtaagat aactttataa gaattctggg tcaaataaaa ttctttgaag aaaacatcca 480 aatgtcattg acttatcaaa tactatcttg gcatataacc tatgaaggca aaactaaaca 540 aacaaaaagc tcacaccaaa caaaaccatc aacttatttt gtattctata acatacgaga 600 ctgtaaagat gtgacagtgt 620 < 210 > 360 < 211 > 431 < 212 > DNA < 213 > Homo sapien < 400 > 360 agccagaaca aaaaaaaaaa gataatatga acatgtgata ttggctgcac acttccagac 60 tgatgaatga tgaacgtgat ggactattgt atggagcaca gagggggaaa tcttcagcaa 120 tactcatcat ttttggccag cagttgtttg atcaccaaac atcatgccag aatactcagc 180 aaaccttctt agctcttgag aagtcaaagt ccgggggaat ttattcctgg caattttaat 240 tggactcctt atgtgagagc agcggctacc cagctggggt ggtggagcga acccgtcact 300 agtggacatg gctcctggta cagtggcaga ggaatacaca accacctaga ggcacatgtg 360 tgatgccaag cgtgacacct gtagcactca aatttgtctt gtttttgtct ttcggtgtgt 420 agattcttag t 431 < 210 > 361 < 211 > 351 < 212 > DNA < 213 > Homo sapien < 400 > 361 acactgattt ccgatcaaaa gaatcatcat ctttaccttg acttttcagg gaattactga 60 actttcttct cagaagatag ggcacagcca ttgccttggc ctcacttgaa gggtctgcat 120 ttgggtcctc tggtctcttg ccaagtttcc cagccactcg agggagaaat atcgggaggt 180 ttgacttcct ccggggcttt cccgagggct tcaccgtgag ccctgcggcc ctcagggctg 240 caatcctgga ttcaatgtct gaaacctcgc tctctgcctg ctggacttct gaggccgtca 300 ctgccactct gtcctccagc tctgacagct cctcatctgt ggtcctgttg t 351
< 210 > 362 < 211 > 463 < 212 > DNA < 213 > Homo sapien < 400 > 362 acttcatcag gccataatgg gtgcctcccg tgagaatcca agcacctttg gactgcgcga 60 tgtagatgag ccggctgaag atcttgcgca tgcgcggctt cagggcgaag ttcttggcgc 120 ccccggtcac agaaatgacc aggttgggtg ttttcaggtg ccagtgctgg gtcagcagct 180 cgtaaaggat ttccgcgtcc gtgtcgcagg acagacgtat atacttccct ttcttcccca 240 gtgtctcaaa ctgaatatcc ccaaaggcgt cggtaggaaa ttccttggtg tgtttcttgt 300 agttccattt ctcactttgg ttgatctggg tgccttccat gtgctggctc tgggcatagc 360 cacacttgca cacattctcc ctgataagca cgatggtgtg gacaggaagg aaggatttca 420 ttgagcctgc ttatggaaac tggtattgtt agcttaaata gac 463
< 210 > 363 < 211 > 653 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (653) < 223 > n = A, T, C or G < 400 > 363 acccccgagt ncctgnctgg catactgnga acgaccaacg acacacccaa gctcggcctc 60 ttctgggtga ctcttggnga catcttcatg aatggcaacc gtgccagwga ggctgtcctc 120 tgggaggcac tacgcaagat gggactgcgt cctggggtga gacatcctct ccttggagat 180 ctaacgaaac ttctcaccta tgagttgtaa agcagaaata cctgnactac agacgagtgc 240 ccccccggaa ccaacagcaa gtatgagttc ctctrgggcc tccgttccta ccatgagasc 300 tagcaagatg naagtgttga gantcattgc agaggttcagaaaagagacc cntcgtgact 360 ggtctgcaca gttcatggag gctgcagatg aggccttgga tgctctggat gctgctgcag 420 ctgaggccga agcccgggct gaagcaagaa cccgcatgggaattggagat gaggctgtgt 480 ntgggccctg gagctgggat gacattgagt ttgaactgct gacctgggat gaggaaggag 540 attttggaga tccntggtcc agaattccat ttaccttctgggccagatac caccagaatg 600 cccgctccag attccctcag acctttgccg gtcccattat tggtcstggt ggt 653
< 210 > 364 < 211 > 401 < 212 > DNA < 213 > Homo sapien < 400 > 364 agacgttaaa actagaggaa ccactctact accacttgtg gaactctcaa aaggtaaatg 60 acaaagccaa tgaatgactc taaaaacaat atttacattt aatggtttgt agacaataaa 120 aaaacaaggt ggatagatct agaattgtaa cattttaaga aaaccatagc atttgacaga 180 tgagaaagct caattataga tgcaaagtta taactaaact actatagtag taaagaaata 240 catttcacac ccttcatata aattcactat cttggcttga ggcactccat aaaatgtatc 300 acgtgcatag taaatcttta tatttgctat ggcgttgcac tagaggactt ggactgcaac 360 aagtggatgc gcggaaaatg aaatcttctt caatagccca 401 g
< 210 > 365 < 211 > 356 < 212 > DNA < 213 > Homo sapien < 400 > 365 ccagtgtcat atttgggctt aaaatttcaa gaagggcact tcaaatggct ttgcatttgc 60 atgtttcagt gctagagcgt aggaatagac cctggcgtcc actgtgagat gttcttcagc 120 taccagagca tcaagtctct gcagcaggtc attcttgggt aaagaaatga cttccacaaa 180 ctctccatcc cctggctttg gcttcggcct tgcgttttcg gcatcatctc cgttaatggt 240 gactgtcacg atgtgtatag tacagtttga tccatacaga caagcctggg ccgctggaga 300 acattcggca atgtcccctt tgtagccagt ttcttcttcg agctcccgga gagcag _ 356 < 210 > 366 < 211 > 1851 < 212 > DNA < 213 > Homo sapien < 400 > 366 tcatcaccat tgccagcagc ggcaccgtta gtcaggtttt ctgggaatcc cacatgagta 60 cttccgtgtt cttcattctt cttcaatagc cataaatctt ctagctctgg ctggctgttt 120 tcacttcctt taagcctttg tgactcttcc tctgatgtca gctttaagtc ttgttctgga 180 ttgctgtttt cagaagagat ttttaacatc tgtttttctt tgtagtcaga aagtaactgg 240 caaattacat gatgatgact agaaacagca tactctctgg ccgtctttcc agatcttgag 300 aagatacatc aacattttgc tcaagtagag ggctgactat acttgctgat ccacaacata 360 cagcaagtat gagagcagtt cttccatatc tatccagcgc atttaaattc gcttttttct 420 tgattaaaaa tttcaccact tgctgttttt gctcatgtat accaagtagc agtggtgtga 480 ggccatgctt gttttttgat tcgatatcag caccgtataa gagcagtgct ttggccatta 540 attgtagaca atttatcttc gcatagtgta gagtggtatt tccatactca tctggaatat 600 ttggatcagt gccatgttcc agcaacatta acgcacattc atcttcctgg cattgtacgg 660 cctttgtcag agctgtcctc tttttgttgt caaggacatt aagttgacat cgtctgtcca 720 gcacgagttt tactacttct gaattcccat tggcagaggc cagatgtaga gcagtcctct 780 tttgcttgtc cctcttgttc acatccgtgt ccctgagcat gacgatgaga tcctttctgg 840 ggactttacc ccacca GGCA gctctgtgga gcttgtccag atcttctcca tggacgtggt 900 acctgggatc catgaaggcg ctgtcatcgt agtctcccca agcgaccacg ttgctcttgc 960 cagcagggga cgctcccctg agcagtggca gcaccacttg cacctcttgc tcccaagcgt 1020 cttcacagag gagtcgttgt ggtctccaga agtgcccacg ttgctcttgc cgctccccct 1080 gtccatccag ggaggaagaa atgcaggaaa tgaaagatgc atgcacgatg gtatactcct 1140 cagccatcaa acttctggac agcaggtcac ttccagcaag gtggagaaag ctgtccaccc 1200 acagaggatg agatccagaa accacaatat ccattcacaa acaaacactt ttcagccaga 1260 cacaggtact gaaatcatgt catctgcggc aacatggtgg aacctaccca atcacacatc 1320 aagagatgaa tatatctgca gacactgcag caacgtaata ctcttcatcc ataacaaaat 1380 aatataattt tcctctggag ccatatggat gaactatgaa ggaagaactc cccgaagaag 1440 ccagtcgcag agaagccaca ctgaagctct gtcctcagcc atcagcgcca cggacaggar 1500 tgtgtttctt ccccagtgat gcagcctcaa gttatcccga agctgccgca gcacacggtg 1560 gctcctgaga aacaccccag ctcttccggt ctaacacagg caagtcaata aatgtgataa 1620 tcacataaac agaattaaaa gcaaagtcac ataagcatct caacagacac agaaaaggca 1680 tttgacaaaa tccagcatcc ttg tatttat tgttgcagtt ctcagaggaa atgcttctaa 1740 cttttcccca tttagtatta tgttggctgt gggcttgtca taggtggttt ttattacttt 1800 aaggtatgtc ccttctatgc ctgttttgct gagggtttta attctcgtgc c 1851
< 210 > 367 < 211 > 668 < 212 > DNA < 213 > Homo sapien < 400 > 367 caaataygga cttgagcttc agactggccc ttacacasgt caatgttaaa atgaatgcat 60 ttcagtattt tgaagataaa attrgtagat ctataccttg ttttttgatt cgatatcagc 120 accrtataag agcagtgctt tggccattaa tttatctttc attrtagaca gcrtagtgya 180 gagtggtatt tccatactca tctggaatat ttggatcagt gccatgttcc agcaacatta 240 acgcacattc atcttcctgg cattgtacgg ttagacccaa cctgtcagta aaacaaatta 300 catatcttag gaattcaaaa taacattcca cagctttcac caactagtta tatttaaagg 360 tttttatgcc agaaaactca atgtattgaa atcaaaccca cctcatgctg atatagttgg 420 ctactgcata cctttatcag agctgtcctc tttttgttgt caaggacatt aagttgacat 480 cgtctgtcca gcaggagttt tactacttct gaattcccat tggcagaggc cagatgtaga 540 gagagtgaga gcagtcctat agacttttta ggaaattgta tacagccata gtgcactagc 600 gcaatgattc atgtaactgc aaacactgaa tagcctgcta ttactctgcc ttcaaaaaaa aaaaaaaa 660 668
< 210 > 368 < 211 > 1512 < 212 > DNA < 213 > Homo sapien < 400 > 368 gggtcgccca gggggsgcgt gggctttcct cgggtgggtg tgggttttcc ctgggtgggg 60 tgggctgggc trgaatcccc tgctggggtt ggcaggtttt ggctgggatt gacttttytc 120 ttcaaacaga ttggaaaccc ggagttacct gctagttggt gaaactggtt ggtagacgcg 180 atctgttggc tactactggc ttctcctggc tgttaaaagc agatggtggt tgaggttgat 240 tccatgccgg ctgcttcttc tgtgaagaag ccatttggtc tcaggagcaa gatgggcaag _3.0"0" tggtgctgcc gttgcttccc ctgctgcagg gagagcggca agagcaacgt gggcacttct 360 ggagaccacg acgactctgc tatgaagaca agatgggcaa ctcaggagca gtggtgccgc 420 cactgcttcc cctgctgcag ggggagtggc aagagcaacg tgggcgcttc tggagaccac 480 gacgaytctg ctatgaagac actcaggaac aagatgggca agtggtgctg ccactgcttc 540 ccctgctgca gggggagcrg caagagcaag gtgggcgctt ggggagacta cgatgacagt 600 gccttcatgg agcccaggta ccacgtccgt ggagaagatc tggacaagct ccacagagct 660 gcctggtggg gtaaagtccc cagaaaggat ctcatcgtca tgctcaggga cactgacgtg 720 aacaagaagg acaagcaaaa gaggactgct ctacatctgg tgggaattca cctctgccaa _ 7, r8 , r0 'gaagtagtaa aactcstgct ggacagacga tgtcaactta atgtccttga caacaaaaag 840 ag gacagctc tgayaaaggc cgtacaatgc caggaagatg aatgtgcgtt aatgttgctg 900 ctgatccaaa gaacatggca tattccagat gagtatggaa ataccactct rcactaygct 960 rtctayaatg aagataaatt aatggccaaa gcactgctct tatayggtgc tgatatcgaa 1020 tcaaaaaaca aggtatagat ctactaattt tatcttcaaa atactgaaat gcattcattt 1080 taacattgac gtgtgtaagg gccagtcttc cgtatttgga agctcaagca taacttgaat 1140 gaaaatattt tgaaatgacc taattatctm agactttatt ttaaatattg ttattttcaa 1200 agaagcatta gagggtacag tttttttttt ttaaatgcac ttctggtaaa tactttugtt 1260 gaaaacactg aatttgtaaa aggtaatact tactattttt caatttttcc ctcctaggat 1320 ttttttcccc taatgaatgt aagatggcaa aatttgccct gaaataggtt ttacatgaaa 1380 aagttaaaca actccaagaa tgtttcagtg aatagagatc ctgctccttt accaagttcc 1440 taaaaaacag taatagatac gaggtgatgc gcctgtcagt ggcaaggttt aagatatttc tgatctcgtg ce 1500 1512
< 210 > 369 < 211 > 1853 < 212 > DNA < 213 > Homo sapien < 400 > 369 gggtcgccca gggggsgcgt gggctttcct cgggtgggtg tgggttttcc ctgggtgggg 60 tgggctgggc trgaatcccc tgctggggtt ggcaggtttt ggctgggatt gacttttytc 120 ttcaaacaga ttggaaaccc ggagttacct gctagttggt gaaactggtt ggtagacgcg 180 atctgttggc tactactggc ttctcctggc tgttaaaagc agatggtggt tgaggttgat 240 tccatgccgg ctgcttcttc tgtgaagaag ccatttggtc tcaggagcaa gatgggcaag 300 tggtgctgcc gttgcttccc ctgctgcagg gagagcggca agagcaacgt gggcacttct 360 ggagaccacg acgactctgc tatgaagaca ctcaggagca agatgggcaa gtggtgccgc 420 cactgcttcc cctgctgcag ggggagtggc aagagcaacg tgggcgcttc tggagaccac 480 gacgaytctg ctatgaagac actcaggaac aagatgggca agtggtgctg ccactgcttc 540 ccctgctgca gggggagcrg caagagcaag gtgggcgctt ggggagacta cgatgacagy 600 geetteatgg akcccaggta ccacgtccrt ggagaagatc tggacaagct ccacagagct 660 gcctggtggg gtaaagtccc cagaaaggat tgctcaggga ctcatcgtca cackgaygtg 720 aacaagargg acaagcaaaa gaggactgct ctacatctgg tgggaattca cctctgccaa 780 aactcstgct gaagtagtaa ggacagacga tgtcaactta atgtccttga caacaaaaag 840 aggacagctc tgayaa AGGC cgtacaatgc caggaagatg aatgtgcgtt aatgttgctg 900 ctgatccaaa gaacatggca tattccagat gagtatggaa ataccactct rcactaygct 960 rtctayaatg aagataaatt aatggccaaa gcactgctct tatayggtgc tgatatcgaa 1020 agcatggcct tcaaaaaaca cacaccactg ytacttggtr tacatgagea aaaacagcaa 1080 gtsgtgaaat ttttaatyaa gaaaaaagcg aatttaaaat gcrctggata gatatggaag 1140 ractgctctc atacttgctg tatgttgtgg atcagcaagt atagtcagee ytctacttga 1200 gcaaaatrtt gatgtatctt etcaagatet ggaaagacgg ccagagagta tgctgtttct 1260 agtcatcatc atgtaatttg ccagttactt aagaaaaaca tctgactaca gatgttaaaa 1320 aaaacagcaa atetettetg tecagaacaa gacttaaagc ggaagagtca tgacatcaga 1380 aaggaagtga caaaggctta aaacagccag ccagaggcat ggaaactttt aaatttaaac 1440 atgttttttt ttttggttta aataatatta tttttgcctt gatagtecca aatgaaatwa 1500 cctatgagac taggctttga gaatcaatag attctttttt taagaatctt ttggctagga 1560 gcggtgtctc acgcctgtaa ttccagcacc ttgagaggct gaggtgggca gatcaegaga ~ 1620 tcaggagatc gagaccatcc tggctaacac ggtgaaaccc catctctact aaaaatacaa 1680 aaaettaget gggtgtggtg g cgggtgcct gtagtcccag rgctgaggca ctactcagga 1740 ggagaatggc atgaacccgg gaggtggagg ttgcagtgag ccgagatccg ccactacact 1800 tgacagagea ccagcctggg agactctgtc tcaaaaaaaa aaaaaaaaaa aaa 1853
< 210 > 370 < 211 > 2184 < 212 > DNA < 213 > Homo sapien < 400 > 370 ttaaaaccct ggcacgagaa cagcaaaaca ggcatagaag ggacatacct taaagtaata 60 aaaaccacct atgacaagcc cacagccaac ataatactaa atggggaaaa gttagaagea 120 gaactgcaac tttcctctga aataaataca aggatgctgg attttgtcaa atgccttttc 180 tgtgtctgtt gagatgetta tgtgactttg cttttaattc tgtttatgtg attatcacat 240 gcctgtgtta ttattgactt gaccggaaga gctggggtgt ttctcaggag ccaccgtgtg 300 ctgcggcagc ttcgggataa cttgaggctg catcactggg gaagaaacac aytcctgtcc 360 tagctgagga gtggcgctga cagaccttca gtgtggcttc tctgcgactg gcttcttcgg 420 ggagttcttc cttcatagtt catccatatg gctccagagg aaaattatat tattttgtta 480 tggatgaaga gtartacgtt gtgcagatat actgcagtgt cttcatctct tgatgtgtga 540 ttgggtaggt tccaccatgt tgccgcagat aacatgattt cagtacctgt gtctggctga 600 aaagtgtttg tttgtgaatg gatattgtgg tttctggatc tcatcctctg tgggtggaca 660 ecttgctgga gctttctcca agtgacctgc tgtccagaag tttgatggct gaggagtata 720 tgcatctttc ccatcgtgca atttcctgca cctggatgga tttcttcctc cagggggagc 780 ggcaagagca acgcgggcac ttctggagac cacaacgact cctctgtgaa gacgcttggg 840 agcaagaggt gcaagt ggtg ctgccactgc ttcccctgct gcaggggagc ggcaagagca 900 acgtggtcgc ttggggagac tacgatgaca gcgccttcat ggatcccagg taccacgtcc 960 atggagaaga tctggacaag ctccacagag ctgcctggtg gggtaaagtc cccagaaagg 1020 atctcatcgt catgctcagg gacacggatg tgaacaagag ggacaagcaa aagaggactg 1080 ctctacatct ggcctctgcc aatgggaatt cagaagtagt aaaactcgtg ctggacagac 1140 gatgtcaact taatgtcctt gacaacaaaa agaggacagc tctgacaaag gccgtacaat 1200 gccaggaaga tgaatgtgcg ttaatgttgc tggaacatgg cactgatcca aatattccag 1260 atgagtatgg aaataccact ctacactatg tgaagataaa ctgtctacaa ttaatggcca 1320 aagcactgct cttatacggt gctgatatcg aatcaaaaaa caagcatggc ctcacaccac 1380 tgctacttgg tatacatgag caaaaacagc aagtggtgaa atttttaatc aagaaaaaag 1440 cgaatttaaa tgcgctggat agatatggaa gaactgctct catacttgct gtatgttgtg 1500 gatcagcaag tatagtcagc cctctacttg agcaaaatgt tgatgtatct tctcaagatc 1560 tggaaagacg gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact 1620 ttctgactac aaagaaaaac agatgttaaa aatctcttct atccagaaca gaaaacagca 1680 agacttaaag ctgacatcag agg aagagtc acaaaggctt aaaggaagtg aaaacagcca 1740 gccagaggca tggaaacttt taaatttaaa cttttggttt aatgtttttt ttttttgcct 1800 taataatatt agatagtccc aaatgaaatw acctatgaga ctaggctttg agaatcaata 1860 gattcttttt ttaagaatct tttggctagg agcggtgtct cacgcctgta attccagcac 1920 cttgagaggc tgaggtgggc agatcacgag atcaggagat cgagaccatc ctggctaaca 1980 cggtgaaacc ccatctctac taaaaataca aaaacttagc tgggtgtggt agcgggtgcc 2040 tgtagtccca gctactcagg argctgaggc aggagaatgg catgaacccg ggaggtggag 2100 gttgcagtga gccgagatcc gccactacac tccagcctgg gtgacagagc aagactctgt 2160 ctcaaaaaaa aaaaaaaaaa aaaa 2184
< 210 > 371 < 211 > 1855 < 212 > DNA < 213 > Homo sapien < 220 > < 221 > diverse feature < 222 > (1) ... (1855) < 223 > n = A, T, C or G < 400 > 371 tgcacgcatc ggccagtgtc tgtgccacgt acactgacgc cccctgagat gtgcacgccg "60 cacgcgcacg ttgcacgcgc ggcagcggct tggctggctt gtaacggctt gcacgcgcac 120 gccgcccccg cataaccgtc agactggcct gtaacggctt gcaggcgcac gccgcacgcg 180 cgtaacggct tggctgccct gtaacggctt gcacgtgcat gctgcacgcg cgttaacggc 240 ttggctggca tgtagccgct tggcttggct ttgcattytt tgctkggctk ggcgttgkty 300 tcttggattg acgcttcctc cttggatkga cgtttcctcc ttggatkgac gtttcytyty 360 tcgcgttcct ttgctggact tgacctttty tctgctgggt ttggcattcc tttggggtgg 420 gctgggtgtt ttctccgggg gggktkgccc ttcctggggt gggcgtgggk cgcccccagg 480 gggcgtgggc tttccccggg tgggtgtggg ttttcctggg gtggggtggg ctgtgctggg 540 atccccctgc tggggttggc agggattgac ttttttcttc aaacagattg gaaacccgga 600 gtaacntgct agttggtgaa actggttggt agacgcgatc tgctggtact actgtttctc 660 ctggctgtta aaagcagatg gtggctgagg ttgattcaat gccggctgct tcttctgtga 720 agaagccatt tggtctcagg agcaagatgg gcaagtggtg cgccactgct tcccctgctg 780 ggcaagagca cagggggagc acgtgggcac ttctggagac cacaacgact ccrctgtgaa 840 gacgcttggg agca agaggt gcaagtggtg ctgcccactg cttcccccgc tgcaggggag 900 cggcaaaagc aacgtggkcg cttggggaga ctacgatgac agcgccttca tggakcccag 960 gtaccacgtc crtggagaag atctggacaa gctccacaga gctgcctggt ggggtaaagt 1020 ccccagaaag gatctcatcg tcatgctcag ggacactgay rggacaagca gtgaacaaga 1080 aaagaggact gctctacatc tggcctctgc caatgggaat tcagaagtag taaaactcgt 1140 gctggacaga cgatgtcaac ttaatgtcct tgacaacaaa aagaggacag ctctgacaaa 1200 ggccgtacaa tgccaggaag atgaatgtgc gttaatgttg ctggaacatg gcactgatcc 1260 aaatattcca gatgagtatg gaaataccac tctacactat atgaagataa gctgtctaca 1320 attaatggcc aaagcactgc tcttatacgg tgctgatatc gaatcaaaaa acaaggtata 1380 ttttatcttc gatctactaa aaaatactga aatgcattca ttttaacatt gacgtgtgta 1440 agggccagtc ttccgtattt ggaagctcaa gcataacttg aatgaaaata ttttgaaatg 1500 acctaattat ctaagacttt attttaaata ttgttatttt ttagagggta caaagaagca 1560 cagttttttt tttttaaatg cacttctggt aaatactttt gttgaaaaca ctgaatttgt 1620 aaaaggtaat acttactatt tttcaatttt tccctcctag gatttttttc ccctaatgaa 1680 tgtaagatgg caaaatttgc cctgaaatag gttttacatg aaaactccaa gaaaagttaa 1740 acatgtttca gtgaatagag atcctgctcc tttggcaagt tcctaaaaaa cagtaataga 1800 tacgaggtga tgcgcctgtc agtggc aagg tttaagatat ttctgatctc gtgcc 1855 <; 210 > 372 < 211 > 1059 < 212 > DNA < 213 > Homo sapien < 400 > 372 gcaacgtggg cacttctgga gaccacaacg actcctctgt gaagacgctt gggagcaaga 60 ggtgcaagtg gtgctgccca ctgcttcccc tgctgcaggg gagcggcaag agcaacgtgg 120 gcgcttgrgg agactmcgat gacagygcct tcatggagcc caggtaccac gtccgtggag 180 aagatctgga caagctccac agagctgccc tggtggggta aagtccccag aaaggatctc 240 atcgtcatgc tcagggacac tgaygtgaac aagarggaca agcaaaagag gactgctcta 300 catctggcct ctgccaatgg gaattcagaa gtagtaaaac tcstgctgga cagacgatgt 360 tccttgacaa caacttaatg acagctctga caaaaagagg yaaaggccgt acaatgccag 420 gaagatgaat gtgcgttaat gttgctggaa catggcactg atccaaatat tccagatgag 480 ccactctrca tatggaaata ctaygctrtc tayaatgaag ataaattaat ggccaaagca 540 ctgctcttat ayggtgctga tatcgaatca aaaaacaagg tatagatcta ctaattttat 600 ctgaaatgca cttcaaaata ttcattttaa cattgacgtg tgtaagggcc agtcttccgt 660 tcaagcataa atttggaagc aatattttga cttgaatgaa ttatctaaga aatgacctaa 720 aatattgtta ctttatttta ttttcaaaga agcattagag ggtacagttt ttttttttta 780 aatgcacttc tggtaaatac ttttgttgaa aacactgaat ttgtaaaagg taatacttac 840 tatttttcaa tttttc cctc ctaggatttt tttcccctaa tgaatgtaag atggcaaaat 900 ttgccctgaa ataggtttta catgaaaact ccaagaaaag ttaaacatgt ttcagtgaat 960 agagatcctg ctcctttggc aagttcctaa aaaacagtaa tagatacgag gtgatgcgcc 1020 tgtcagtggc aaggtttaag atatttctga tctcgtgcc 1059 < 210 > 373 < 211 > 1155 < 212 > DNA < 213 > Homo sapien < 400 > 373 atggtggttg aggttgattc catgccggct gcctcttctg tgaagaagcc atttggtctc 60 aggagcaaga tgggcaagtg gtgctgccgt tgcttcccct gctgcaggga gagcggcaag 120 agcaacgtgg gcacttctgg agaccacgac gactctgcta tgaagacact caggagcaag 180 atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240 ggcgcttctg gagaccacga cgactctgct atgaagacac tcaggaacaa gatgggcaag 300 tggtgctgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg 360 ggagactacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatctg 420 gacaagctcc acagagctgc ctggtggggt aaagtcccca gaaaggatct catcgtcatg 480 ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 540 tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat 600 gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa 660 tgttgctgga tgtgcgttaa acatggcact gatccaaata ttccagatga gtatggaaat 720 accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta 780 tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgta 840 catgagcaaa aacagc AAGT ttaatcaaga cgtgaaattt tttaaatgca aaaaagcgaa 900 ctggatagat atggaaggac tgctctcata cttgctgtat gttgtggatc agcaagtata 960 tacttgagca gtcagtcttc aaatattgat gtatcttctc aagatctatc tggacagacg 1020 gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac 1080 agatgctaaa aaagaaaaac aatctcttct gaaaacagca tgtctcaaga atccagaaaa accagaaata AATAA 1140 1155 < 210 > 374 < 211 > 2000 < 212 > DNA < 213 > Homo sapien < 400 > 374 atggtggttg aggttgattc catgccggct gcctcttctg taaagaagcc atttggtctc 60 aggagcaaga tgggcaagtg gtgctgccgt tgcttcccct gctgcaggga gagcggcaag 120 agcaacgtgg gcacttctgg agaccacgac gactctgcta tgaagacact caggagcaag 180 atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240 ggcgcttctg gacaccacga cgactctgct atgaagacac tcaggaae & to gatgggcaag 300 tggtgctgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg 360 ggagactacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatctg 420 gacaagctcc acagagctgc ctggtggggt aaagtcccca gaaaggatct catcgtcatg 480 ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 540 tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat 600 gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa 660 tgttgctgga tgtgcgttaa acatggcact gatccaaata ttccagatga gtatggaaat 720 accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta 780 tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgta 840 catgagcaaa aa cagcaagt cgtgaaattt ttaatcaaga aaaaagcgaa tttaaatgca 900 ctggatagat atggaaggac tgctctcata cttgctgtat gttgtggatc agcaagtata 960 gtcagccttc tacttgagca aaatattgat gtatcttctc aagatctatc tggacagacg 1020 gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac 1080 agatgctaaa aaagaaaaac gaaaacagca aatctcttct atccagaaca agacttaaag 1140 ctgacatcag aggaagagtc acaaaggttc aaaggcagtg aaaatagcca gccagagaaa 1200 atgtctcaag aaccagaaat aaataaggat ggtgatagag aggttgaaga agaaatgaag 1260 gtaataatgt aagcatgaaa gggattacta gaaaacctga ctaatggtgt cactgctggc! 320 aatggtgata atggattaat tcctcaaagg aagagcagaa cacctgaaaa tcagcaattt 1380 aaagtgaaga cctgacaacg gtatcacaga tagtttctga atttgcgaat ctacaaagaa 1440 aaacagatgc caaaatactc ttctgaaaac agcaacccag aacaagactt aaagctgaca 1500 tcagaggaag agtcacaaag gcttgagggc agtgaaaatg gccagccaga gctagaaaat 1560 tttatggcta tcgaagaaat gaagaagcac ggaagtactc atgtcggatt cccagaaaac 1620 ctgactaatg gtgccactgc tggcaatggt gatgatggat taattcctcc aaggaagagc 1680 agaacacctg aaagccagca atttcctgac actgagaatg aagagtatca cagtgacgaa 1740 ctcagaagca caaaatgata attttgtgaa gaacagaaca ctggaatatt acacgatgag 1800 attctgattc atgaagaaaa gcagat agaa gtggttgaaa aaatgaattc tgagctttct 1860 cttagttgta agaaagaaaa agacatcttg catgaaaata atacgttgcg ggaagaaatt 1920 gccatgctaa gactggagct agacacaatg aaacatcaga gccagctaaa aaaaaaaaaa 1980 aaaaaaaaaa aaaaaaaaaa 2000
< 210 > 375 < 211 > 2040 < 212 > DNA < 213 > Homo sapien < 400 > 375 atggtggttg aggttgattc catgccggct gcctcttctg tgaagaagcc atttggtctc 60 aggagcaaga tgggcaagtg gtgctgccgt tgcttcccct gctgcaggga gagcggcaag 120 agcaacgtgg gcacttctgg agaccacgac gactctgcta tgaagacact caggagcaag 180 atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240 ggcgcttctg gagaccacga cgactctgct atgaagacac tcaggaacaa gatgggcaag 300 tggtgctgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg 360 ggagactacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatctg 420 gacaagctcc acagagctgc ctggtggggt aaagtcccca gaaaggatct catcgtcatg 480 ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 540 tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat 600 gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa 660 tgttgctgga tgtgcgttaa acatggcact gatccaaata ttccagatga gtatggaaat 720 accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta 780 tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgta 840 catgagcaaa aacag caagt ttaatcaaga cgtgaaattt tttaaatgca aaaaagcgaa 900 ctggatagat atggaaggac tgctctcata cttgctgtat gttgtggatc agcaagtata 960 tacttgagca gtcagccttc aaatattgat gtatcttctc aagatctatc tggacagacg 1020 gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac 1080 agatgctaaa aaagaaaaac gaaaacagca aatctcttct atccagaaca agacttaaag 1140 ctgacatcag aggaagagtc acaaaggttc aaaggcagtg aaaatagcca gccagagaaa 1200 atgtctcaag aaccagaaat aaataaggat ggtgatagag aggttgaaga agaaatgaag 1260 aagcatgaaa gtaataatgt gggattacta gaaaacctga ctaatggtgt cactgctggc 1320 aatggtgata atggattaat tcctcaaaag aagagcagaa cacctgaaaa tcagcaattt 1380 aaagtgaaga cctgacaacg gtatcacaga atttgcgaat tagtttctga ctacaaagaa 1440 aaacagatgc caaaatactc ttctgaaaac agcaacccagaacaagactt aaagctgaca 1500 tcagaggaag agtcacaaag gcttgagggc agtgaaaatggccagccaga gaaaagatct 1560 caagaaccag aaataaataa ggatggtgat agagagctagaaaattttat ggctatcgaa 1620 gaaatgaaga agcacggaag tactcatgtc ggattcccagaaaacctgac taatggtgcc 1680 atggtgatga actgctggca tggatt TAs cctccaagga agagcagaac acctgaaagc 1740 ctgacactga cagcaatttc gaatgaagag tatcacagtg acgaacaaaa tgatactcag 1800 gtgaagaaca aagcaatttt gaacactgga atattacacg atgagattct gattcatgaa 1860 gaaaagcaga tagaagtggt tgaaaaaatg aattctgagc tttctcttag ttgtaagaaa 1920 tcttgcatga gaaaaagaca aaatagtacg ttgcgggaag aaattgccat gctaagactg caatgaaaca 1980 aaaaaaaaaa aaaaaaaaaa gagctagaca ctaaaaaaaa tcagagccag 2040 < 210 > 376 < 211 > 329 < 212 > PRT < 213 > Homo sapien < 400 > 376 Met Asp He Val Val Ser Gly Ser His Pro Leu Trp Val Asp Ser Phe 1 5 10 15 Leu His Leu Wing Gly SerAsp Leu Leu Ser Arg Ser Leu Met Wing Glu 20 25 30 Glu Tyr Thr He Val His Wing Being Phe He Ser Cys He Ser Ser Ser 35 40 45 Leu Asp Gly Gln Gly GluArg Gln Glu Gln Arg Gly His Phe Trp Arg 50 55 60 Pro Gin Arg Leu Leu Cys Glu Asp Wing Trp Glu Gln Glu Val Gln Val 65 70 75 80 Val Leu Pro Leu Leu Prc Leu Leu Gln Gly Ser Gly Lys Ser Asn Val 85 90 95 Val Wing Trp Gly Asp TyrAsp Asp Ser Wing Phe Met Asp Pro Arg Tyr 100 105 110 His Val His Gly Glu Asp Leu Asp Lys Leu His Arg Wing Wing Trp Trp 115 120 125 Gly Lys Val Pro Arg Lys Asp Leu He Val Met Leu Arg Asp Thr Asp 130 135 140"? L 2 = ~? Lys Arg Asp Lys Gln Lys Arg Thr Ala Leu His Leu Ala Ser 145 150 155 160 Wing Asn Gly Asn Ser GluVal Val Lys Leu Val Leu Asp Arg Arg Cys 165 170 175 Gln Leu Asn Val Leu AspAsn Lys Lys Arg Thr Wing Leu Thr Lys Wing 180 185 190 Val Gln Cys Gln Glu AspGlu Cys Ala Leu Met Leu Leu Glu His Gly 195 200 205 Thr A sp Pro Asn He ProAsp Glu Tyr Gly Asn Thr Thr Leu His Tyr 210 215 220 1_. "1" _ r: »= - Giu Asp Lys Leu Met Ala Lys Ala Leu Leu Leu Tyr 225 230 235 240 Gly .Ala Asp lie Glu Ser Lys Asn Lys His Gly Leu Thr Pro Leu Leu 245 250 255 Leu Gly He His Glu Gln Lys Gln Gln Val Val Lys Phe Leu He Lys
260 265 270 Lys Lys Wing Asn Leu Asn Wing Leu Asp Arg Tyr Gly Arg Thr Wing Leu 275 280 285 He Leu Wing Val Cys Cys Gly Ser Wing Being He Val Ser Pro Leu Leu
290 295 300 Glu Gln Asn Val Asp Val Ser Ser Gln Asp Leu Glu Arg Arg Pro Glu 305 310 315 320
Be Met Leu Phe Leu Val He He Met 325 < 210 > 377 < 211 > 148 < 212 > PRT < 213 > Homo sapien < 220 > < 221 > VARIANT < 222 > ( 1 ) . . . (148) < 223 > Xaa = Any amino acid < 400 > 377 Met Thr Xaa Pro Ser Trp Ser Pro Gly Thr Thr Ser Val Glu Lys He 1 5 10 15 Trp Thr Ser Ser Thr Glu Leu Pro Trp Trp Gly Lys Val Pro Arg Lys
25 30 Asp Leu He Val Met Leu Arg Asp Thr Asp Val Asn Lys Xaa Asp Lys
40 45 Gln Lys Arg Thr Wing Leu His Leu Wing Being Wing Asn Gly Asn Ser Glu 50 55 60 Val Val Lys Leu Xaa Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp 65 70 75 80
Asn Lys Arg Thr Ala Leu Xaa Lys Ala Val Gln Cys Gln Glu Asp 85 90 95 Glu Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro Asn He Pro
100 105 110 Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala Xaa Tyr Asn Glu Asp
115 120 125 Lys Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp He Glu Ser 130 135 140 Lys Asn Lys Val 145 < 210 > 378 < 211 > 1719 < 212 > PRT < 213 > Homo sapien < 400 > 378 Met Val Val Glu Val Asp Ser Met Pro Ala Wing Ser Ser Val Lys Lys
1 5 10 15
Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe
25 30 Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp 35 40 45 Hi s -Asp Asp Ser Wing Met Lys Thr Leu Arg Ser Lys Met Gly Lys T GD
50 55 60 Cys. Arg Hi s Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Va l 65 70 75 8C Gly .Ala Se r Gly Asp His Asp Asp Se r Aia Met Lys Thr Leu Arg As n 85 90 95
Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser
100 105 110 Gly Lys Ser Lys Val Gly Wing Trp Gly Asp Tyr Asp Asp Ser Ala Phe
115 120 125 Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His
130 135 140 Arg Wing Wing Trp Trp Gly Lys Val Pro Arg Lys Asp Leu He Val Met
145 150 155 160
Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln Lys Arg Thr Wing 165 170 175
Leu His Leu Ala Be Wing Asn Gly Asn Ser Glu Val Val Lys Leu Leu 180 185 190 Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr
195 200 205 Ala Leu He Lys Ala Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met 210 215 220 Leu Leu Glu His Gly Thr Asp Pro Asn He Pro Asp Glu Tyr Gly Asn
225 230 235 240
Thr Thr Leu His Tyr Wing He Tyr Asn Glu Asp Lys Leu Met Wing Lys 245 250 255
Ala Leu Leu Leu Tyr Gly Ala Asp He Glu Ser Lys Asn Lys His Gly 260 265 270
Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys Gln Gln Val Val 275 280 285 Lys Phe Leu He Lys Lys Lys Wing Asr Leu Asn Wing Leu Asp Arg Tyr
290 295 300 Gly Arg Thr Ala Leu He Leu Ala Val Cys Cys Gly Ser Ala Be He
305 310 315 320
Val Ser Leu Leu Leu Glu Gln Asn He Asp Val Ser Ser Gln Asp Leu 325 330 335
Ser Gly Gln Thr Wing Arg Glu Tyr Wing Val Ser Ser His His His Val
340 345 350
He Cys Gln Leu Leu Being Asp Tyr Lys Glu Lys Gln Met Leu Lys He 355 360 365 Ser Ser Glu Asn Ser Asn Pro Glu Asn Val Ser Arg Thr Arg Asn Lys
370 375 380 Pro Arg Thr His Met Val Val Glu Val Asp Ser Met Pro Pro Wing Ala Ser
385 390 395 400
Ser Val Lys Lys Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys
405 410 415
Cys Arg Cys Phe Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly 420 425 430 Thr Ser Gly Asp His Asp Asp Ser Wing Met Lys Thr Leu Arg Ser Lys
435 440 445 Met Gly Lys Trp Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly
450 455 460 Lys Ser Asn Val Gly Wing Ser Gly Asp His Asp Asp Ser Wing Met Lys
465 470 475 480
Thr Leu Arg Asn Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys 485 490 495
Cys Arg Gly Ser Gly Lys Ser Lys Val Gly Wing Trp Gly Asp Tyr Asp
500 505 510
Asp Ser Wing Phe Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu 515 520 525 Asp Lys Leu His Arg Wing Wing Trp Trp Gly Lys Val Pro Arg Lys Asp 530 535 540 Leu He Val Met Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gin
545 550 555 560
L s Arg Thr Aia Leu His Leu Wing Being Wing Asn Gly Asn Ser Glu Val 565 570 575
Val Lys Leu Leu Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn 580 585 590
Lys Lys Arg Thr Wing Leu He Lys Wing Val Gln Cys Gln Glu Asp Giu 595 600 605 Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro Asn He Pro Asp
610 615 620 Glu Tyr Gly Asn Thr Thr Leu His Tyr Wing He Tyr Asn Glu Asp Lys 625 630 635 640
Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp He Glu Ser Lys
645 650 655
Asn Lys His Gly Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys 660 665 670 Gln Gln Val Val Lys Phe Leu He Lys Lys Lys Wing Asn Leu Asn Wing 675 680 685 Leu Asp Arg Tyr Gly Arg Thr Wing Leu He Leu Wing Val Cys Cys Gly
690 695 700 Being Wing Being He Val Being Leu Leu Leu Glu Gln Asn He Asp Val Ser 705 710 715 720
Being Gln Asp Leu Being Gly Gln Thr Wing Arg Glu Tyr Wing Val Being Ser
725 730 735
His His His Val He Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln 740 745 750 Met Leu Lys He Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys 755 760 765 Leu Thr Ser Glu Glu Glu Ser Gln Arg Phe Lys Gly Ser Glu Asn Ser
770 775 780 Gln Pro Glu Lys Met Ser Gln Glu Pro Glu He Asn Lys Asp Gly Asp 785 790 795 800
Arg Glu Val Glu Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly
805 810 815
Leu Leu Glu Asn Leu Thr Asn Gly Val Thr Wing Gly Asn Gly Asp Asn 820 825 830 Gly Leu He Pro Gln Arg Lys Ser Arg Thr Pro Glu Asn Gln Gln Phe 835 840 845 Pro Asp Asn Glu Ser Glu Glu Tyr His Arg He Cys Glu Leu Val Ser
850 855 860 Asp Tyr Lys Glu Lys Gln Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn 865 870 875 880
Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Leu
885 890 895
Glu Gly Ser Glu Asn Gly Gln Pro Glu Leu Glu Asn Phe Met Wing He 900 905 910 Glu Glu Met Lys Lys His Gly Ser Thr His Val Gly Phe Pro Glu Asn 915 920 925 Leu Thr Asn Gly Ala Thr Ala Gly Asn Gly Asp Asp Gly Leu He Pro
930 935 940 Pro Arg Lys Ser Arg Thr Pro Glu Ser Gln Gln Phe Pro Asp Thr Glu 945 950 955 960
Asn Glu Glu Tyr His Ser Asp Glu Gln Asn Asp Thr Gln Lys Gln Phe
965 970 975
Cys Glu Glu Gln Asn Thr Gly He Leu His Asp Glu He Leu He His 980 985 990 Glu Glu Lys Gln He Glu Val Val Glu Lys Met Asn Ser Glu Leu Ser 995 1000 1005 Leu Ser Cys Lys Lys Glu Lys Asp He Leu His Glu Asn Ser Thr Leu
1010 1015 1020 Arg Glu Glu He Wing Met Leu Arg Leu Glu Leu Asp Thr Met Lys His 1025 1030 1035 1040
Gln Ser Gln Leu Pro Arg Thr His Met Val Val Glu Val Asp Ser Met
1045 1050 1055
Pro Ala Ala Ser Ser Val Lys Lys Pro Phe Gly Leu Arg Ser Lys Met 1060 1065 1070 Gly Lys Trp Cys Cys Arg Cys Phe Pro Cys Cys Arg Glu Ser Gly Lys 1075 1080 1085 Ser. As Val Gly Thr Ser Gly Asp His Asp Asp Be Wing Met Lys Thr
1090 1095 1100 Leu .Arg Ser Lys Met Gly Lys Trp Cys Arg His Cys Phe Pro Cys Cys 1105 1110 1115 1120
Arg Gly Ser Gly Lys Ser Asn Val Gly Wing Ser Gly Asp His Asp Asp
1125 1130 1135
Be Wing Met Lys Thr LeuArg Asn Lys Met Gly Lys Trp Cys Cys His 1140 1145 1150 Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Lys Val Gly Wing Trp
1155 1160 1165 Gly Asp Tyr Asp Asp Being Wing Phe Met Glu Pro Arg Tyr His Val Arg
1170 1175 1180 Gly Glu Asp Leu Asp Lys Leu His Arg Ala Wing Trp Trp Gly Lys Val
1185 1190 1195 1200
Pro Arg Lys Asp Leu He Val Met Leu Arg Asp Thr Asp Val Asn Lys
1205 1210 1215
Lys Asp Lys Gln Lys Arg Thr Wing Leu His Leu Wing Ser Wing Asn Gly 1220 1225 1230 Asn Ser Glu Val Val Lys Leu Leu Leu Asp Arg Arg Cys Gln Leu Asn
1235 1240 1245 Val Leu Asp Asn Lys Lys Arg Thr Ala Leu He Lys Ala Val Gln Cys
1250 1255 1260 Gln Glu Asp Glu Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro
1265 1270 1275 1280
Asn He Pro Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr Wing He Tyr
1285 1290 1295
Asn Glu Asp Lys Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp 1300 1305 1310 He Glu Ser Lys Asn Lys His Gly Leu Thr Pro Leu Leu Leu Gly Val
1315 1320 1325 His Glu Gln Lys Gln Gln Val Val Lys Phe Leu He Lys Lys Lys Wing
1330 1335 1340 Asn Leu Asn Ala Leu Asp Arg Tyr Gly Arg Thr Ala Leu He Leu Ala
1345 1350 1355 1360
Val Cys Cys Gly Ser Ala Ser He Val Ser Leu Leu Leu Glu Gln Asn
1365 1370 1375
He Asp Val Ser Ser Gln Asp Leu Ser Gly Gln Thr Wing Arg Glu Tyr 1380 1385 1390 Wing Val Ser Ser His His His Val He Cys Gln Leu Leu Ser Asp Tyr
1395 1400 1405 Lys Glu Lys Gln Met Leu Lys He Ser Ser Glu Asn Ser Asn Pro Glu 1410 1415 1420 Gln Asp Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Phe Lys Gly 1425 1430 1435 1440
Ser Glu Asn Ser Gln Pro GluLys Met Ser Gln Glu Pro Glu He Asn
1445 1450 1455
Lys Asp Gly Asp Arg GluVal Glu Glu Glu Met Lys Lys His Glu Ser 1460 1465 1470 Asn Asn Val Gly Leu Leu Glu Asn Leu Thr Asn Gly Val Thr Ala Gly
1475 1480 1485 Asn Gly Asp Asn Gly Leu He Pro Gln Arg Lys Ser Arg Thr Pro Glu
1490 1495 1500 Asn Gln Gln Phe Pro Asp 'Asn Glu Ser Glu Glu Tyr His Arg He Cys
1505 1510 1515 1520
Glu Leu Val Ser Asp Tyr Lys Glu Lys Gln Met Pro Lys Tyr Ser Ser
1525 1530 1535
Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu Glu Glu 1540 1545 1550 Ser Gln Arg Leu Glu Gly Ser Glu Asn Gly Gln Pro Glu Lys Arg Ser
1555 1560 1565 Gln Glu Pro Glu He Asn Lys Asp Gly Asp Arg Glu Leu Glu Asn Phe
1570 1575 1580 Met Ala He Glu Glu Met Lys Lys His Gly Ser Thr His Val Gly Phe
1585 1590 1595 1600
Pro Glu Asn Leu Thr Asn Gly Ala Thr Ala Gly Asn Gly Asp Asp Gly
1605 1610 1615
Leu He Pro Pro Arg Lys Ser Arg Thr Pro Glu Ser Gln Gln Phe Pro 1620 1625 1630 Asp Thr Glu Asn GluGlu Tyr His Ser Asp Glu Gln Asn Thr Gln 1635 1640 1645 Lys Gln Phe Cys Glu Glu Gln Asn Thr Gly He Leu His Asp Glu He 5 1650 1655 1660 Leu He His Glu Glu Lys Gln He Glu Val Val Glu Lys Met Asn Ser 1665 1670 1675 1680
Glu Leu Ser Leu Ser Cys Lys Lys Glu Lys Asp He Leu His Glu Asn f 1685 1690 1695 10 Be Thr Leu Arg Glu Glu He Wing Met Leu Arg Leu Glu Leu Asp Thr 1700 1705 1710 Met Lys His Gln Ser Gln Leu 1715 15 < 210 > 379 < 211 > 656 < 212 > PRT < 213 > Homo sapien 20 < 400 > 379 Met Val Val Glu Val Asp Ser Met Pro Ala Wing Ser Val Lys Lys 1 5 10 15 Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe f 20 25 30 25 Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp 35 40 45 His Asp Asp Ser Wing Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp 50 55 60 Cys Arg His Cys Phe Pro Cys CysArg Gly Ser Gly Lys Ser Asn Val 30 65 70 75 80 Gly Wing Ser Gly AspHis Asp Asp Ser Wing Met Lys Thr Leu Arg Asn 85 90 95 Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser 100 105 110 35 Gly Lys Ser Lys Val Gly Wing Trp Gly Asp Tyr Asp Asp Ser Ala Phe 115 120 125 Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His 130 135 140 Arg Wing Wing Trp Trp Gly Lys Val Pro Arg Lys Asp Leu He Val Met 40 145 150 155 160
Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln Lys Arg Thr Wing 165 170 175 Leu His Leu Wing Being Wing Asn Gly Asn Ser Glu Val Val Lys Leu Leu 180 185 190 45 Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr 195 200 205 Wing Leu He Lys Wing Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met 210 215 220 Leu Leu Glu His Gly Thr Asp Pro Asn Pro Pro Asp Glu Tyr Gly Asn 50 225 230 235 240
Thr Thr Leu His Tyr Wing He Tyr Asn Glu Asp Lys Leu Met Wing Lys 245 250 255 Wing Leu Leu Tyr Gly Wing Asp He Glu Ser Lys Asn Lys His Gly 260 265 270 55 Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys Gln Val Val 275 280 285 Lys Phe Leu He Lys Lys Lys Wing Asn Leu Asn Wing Leu Asp Arg Tyr 290 295 300 Gly Arg Thr Wing Leu He Leu Wing Val Cys Cys Gly Ser Wing Ser He 60 305 310 315 320
Val Ser Leu Leu Leu Glu Gln Asn He Asp Val Ser Ser Gln ISD Leu 325 330: 3rd Se. Gly G1- br Ala rq Glu Tvr Wing Val Ser Ser r_s His - s Val 340 345 350 He Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln Met Leu Lys He 355 360 365 Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu 370 375 380 Glu Glu Ser Gln Arg Phe Lys Gly Ser Glu Asn Ser Gln Pro Glu Lys
385 390 395 400
Met Ser Gln Glu Pro Glu He Asn Lys Asp Gly Asp Arg Glu Val Glu
405 410 415
Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly Leu Leu Glu Asn 420 425 430 Leu Thr Asn Gly Val Thr Wing Gly Asn Gly Asp Asn Gly Leu He Pro
435 440 445 Gln Arg Lys Ser Arg Thr Pro Glu Asn Gln Gln Phe Pro Asp Asn Glu 450 455 460 Ser Glu Glu Tyr His Arg He Cys Glu Leu Val Ser Asp Tyr Lys Glu
465 470 475 480
Lys Gln Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp 485 490 495
Leu Lys Leu Thr SerGlu Glu Glu Ser Gln Arg Leu Glu Gly Ser Glu 500 505 510 Asn Gly Gln Pro Glu Leu GlulAsn Phe Met Wing He Glu Glu Met Lys
515 520 525 Lys His Gly Ser Thr His ValGly Phe Pro Glu Asn Leu Thr Asn Gly
530 535 540 Ala Thr Ala Gly Asn Gly Asp Asp Gly Leu He Pro Pro Arg Lys Ser
545 550 555 560
Arg Thr Pro Glu Ser Gln Gln Phe Pro Asp Thr Glu Asn Glu Glu Tyr 565 570 575
His Ser Asp Glu Gln Asn Asp Thr Gln Lys Gln Phe Cys Glu Glu Gln 580 585 590 Asn Thr Gly He Leu His Asp Glu He Leu He His Glu Glu Lys Gln 595 600 605 He Glu Val Val Glu Lys Met Asn Ser Glu Leu Ser Leu Ser Cys Lys
610 615 620 Lys Glu Lys Asp He Leu His Glu Asn Ser Thr Leu Arg Glu Glu He
625 630 635 640
Wing Met Leu Arg Leu Glu Leu Asp Thr Met Lys His Gln Ser Gln Leu
645 650 655 < 210 > 380 < 211 > 671 < 212 > PRT < 213 > Homo sapien < 400 > 380 Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys 1 5 10 15
Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe 20 25 30 Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp
40 45 His Asp Asp Ser Wing Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp 50 55 60 Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val 65 70 75 80
Gly Wing Ser Gly Asp His Asp Asp Ser Wing Met Lys Thr Leu Arg Asn
85 90 95
Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser 100 105 110 Gly Lys Ser Lys Val Gly Wing Trp Gly Asp Tyr Asp Asp Ser Ala Phe
115 120 125 Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His 130 135 140 Arg Wing Wing Trp Trp Gly Lys Val Pro Arg Lys Asp Leu He Val Met
145 150 155 160
Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln Lys Arg Thr Wing 165 170 175
Leu His Leu Ala Be Wing Asn Gly Asn Ser Glu Val Val Lys Leu Leu 180 185 190 Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr
195 200 205 Ala Leu He Lys Ala Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met 210 215 220 Leu Leu Glu His Gly Thr Asp Pro Asn He Pro Asp Glu Tyr Gly Asn
225 230 235 240
Thr Thr Leu His Tyr Wing He Tyr Asn Glu Asp Lys Leu Met Wing Lys 245 250 255
Wing Leu Leu Leu Tyr Gly Wing Asp He Glu Being Lys Asn Lys His Gly 260 265 270 Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys Gln Gln Val Val
275 280 290 Lys Phe Leu He Lys Lys Lys Wing Asn Leu Asn Wing Leu Asp Arg Tyr
290 295 300 Gly Arg Thr Ala Leu He Leu Ala Val Cys Cys Gly Ser Ala Be He
305 310 315 320
Val Ser Leu Leu Leu Glu Gln Asn He Asp Val Ser Ser Gln Asp Leu 325 330 335
Ser Gly Gln Thr Wing Arg Glu Tyr Wing Val Ser Ser His His His Val 340 345 350 He Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln Met Leu Lys He 355 360 365 Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu 370 375 380 Glu Glu Ser Gln Arg Phe Lys Gly Ser Glu Asn Ser Gln Pro Glu Lys
385 390 395 400
Met Ser Gln Glu Pro Glu He Asn Lys Asp Gly Asp Arg Glu Val Glu
405 410 415
Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly Leu Leu Glu Asn
420 425 430 Leu Thr Asn Gly Val Thr Ala Gly Asn Gly Asp Asn Gly Leu He Pro
435 440 445 Gln Arg Lys Ser Arg Thr Pro Glu Asn Gln Gln Phe Pro Asp Asn Glu 450 455 460 Ser Glu Glu Tyr His Arg He Cys Glu Leu Val Ser Asp Tyr Lys Glu
465 470 475 480
Lys Gln Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp 485 490 495
Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Leu Glu Gly Ser Glu 500 505 510 Asn Gly Gln Pro Glu Lys Arg Ser Gln Glu Pro Glu He Asn Lys Asp 515 520 525 Gly Asp Arg Glu Leu Glu Asn Phe Met Wing He Glu Glu Met Lys Lys 530 535 540 His Gly Ser Thr His Val Gly Phe Pro Glu Asn Leu Thr Asn Gly Ala
545 550 555 560
Thr Ala Gly Asn Gly Asp Asp Gly Leu He Pro Pro Arg Lys Ser Arg
565 570 575
Thr Pro Glu Ser Gln Gln Phe Pro Asp Thr Glu Asn Glu Glu Tyr His 580 585 590
Be Asp Glu Gln Asn Asp Thr Gln Lys Gln Phe Cys Glu Glu Gln Asn 595 600 605 Thr Gly He Leu His Psp Glu He Leu He His Glu Glu Lys Gln He clO 615 620 Glu Val Vai Glu Lys Met? Sn Ser Glu Leu Ser Leu Ser Cys Lys Lys
625 630 635 640
Glu Lys Aso He Leu Fis Glu Asn Ser Thr Leu Arg Glu Glu He Wing 645 650 655 Met Leu Arg Leu Glu Leu Asp Thr Met Lys His Gln Ser Gln Leu 660 665 670 < 210 > 381 < 211 > 251 < 212 > DNA < 213 > Homo sapien < 400 > 381 ggagaagcgt ctgctggggc aggaaggggt ttccctgccc tctcacctgt ccctcaccaa 60 ggtaacatgc ttcccctaag ggtatcccaa cccaggggcc tcaccatgac ctctgagggg 120 ccaatatccc aggagaagca ttggggagtt gggggcaggt gaaggaccca ggactcacac 180 atcctgggcc tccaaggcag aggagagggt cctcaagaag gtcaggagga aaatccgtaa caagcagtca g 251 240
< 210 > 382 < 211 > 3279 < 212 > DNA < 213 > Homo sapiens < 400 > 382 cttcctgcag cccccatgct ggtgaggggc acgggcagga acagtggacc caacatggaa 60 atgctggagg gtgtcaggaa gtgatcgggc tctggggcag ggaggagggg tggggagtgt 120 cactgggagg ggacatcctg cagaaggtag gagtgagcaa acacccgctg caggggaggg 180 gagagccctg cggcacctgg gggagcagag ggagcagcac ctgcccaggc ctgggaggag 240 gggcctggag ggcgtgagga ggagcgaggg ggctgcatgg ctggagtgag ggatcagggg 300 gatggcctca cagggcgcga cacagggaag agagggcccc tcctgcaggg cctcacctgg 360 gccacaggag gacactgctt ttcctctgag gagtcaggag ctgtggatgg tgctggacag 420 aagaaggaca caggtgtcca gggcctggct gaggctgtcg ctggcttccc tttgggatca 480 gactgcaggg agggagggcg gcagggttgt ggggggagtg acgatgagga tgacctgggg 540 gtggctccag gccttgcccc tgcctgggcc ctcacccagc ctecctcaca gtctcctggc 600 cctcagtctc tcccctccac tccatcctcc atctggcctc agtgggtcat tctgatcact 660 gaactgacca tacccagccc tgcccacggc cctccatggc tccccaatgc cctggagagg 720 tcagagagta ggacatctag gtcctgaaga ggtggcctct gcgatgtgcc tgtgggggca 780 gcatcctgca gatggtcccg gccctcatcc tgctgacctg tctgcaggga ctgtcctcct 840 ggaccttgcc ccttg tgcag gagctggacc ctgaagtccc ctccccatag gccaagactg 900 gagccttgtt ccctctgttg gactccctgc ccatattctt gtgggagtgg gttctggaga 960 catttctgtc tgttcctgag agctgggaat tgctctcagt catctgcctg cgcggttctg 1020 agagatggag ttgcctaggc agttattggg gccaatcttt ctcactgtgt ctctcctcct 1080 ttacccttag ggtgattctg ggggtccact tgtctgtaat ggtgtgcttc aaggtatcac 1140 atcatggggc cctgagccat gtgccctgcc tgaaaagcct gctgtgtaca ccaaggtggt 1200 gcattaccgg aagtggatca aggacaccat cgcagccaac ccctgagtgc ccctgtccca 1260 cccctacctc tagtaaattt aagtccacct cacgttctgg catcacttgg cctttctgga 1320 tgctggacac ctgaagcttg gaactcacct ggccgaagct cgagcctcct gagtcctact 1380 gacctgtgct ttctggtgtg gagtccaggg ctgctaggaa aaggaatggg cagacacagg 1440 tgtttctgaa tgtatgccaa atgggtataa tttcgtcctc tccttcggaa cactggctgt 1500 ttctcgctca ctctgaagac gtttcagtga ggacacacac aaagacgtgg gtgaccatgt 1560 tgtttgtggg gtgcagagat gggaggggtg gggcccaccc tggaagagtg gacagtgaca 1620 actctctaca caaggtggac gatcactgag gataagctgg agccacaatg catgaggcac 1680 acacacagca aggttgacgc tg taaacata gcccacgctg tcctgggggc actgggaagc 1740 ctagataagg ccgtgagcag aaagaagggg aggatcctcc tatgttgttg aaggagggac 1800 tagggggaga aactgaaagc tgattaatta caggaggttt gttcaggtcc cccaaaccac 1860 cgtcagattt gatgatttcc tagcaggact tacagaaata aagagctatc atgctgtggt 1920 ttattatggt ttgttacatt gataggatac atactgaaat cagcaaacaa aacagatgta 1980 tagattagag tgtggagaaa acagaggaaa acttgcagtt acgaagactg gcaacttggc 2040 tttactaagt tttcagactg gcaggaagtc aaacctatta ggctgaggac cttgtggagt 2100 gtagctgatc cagctgatag aggaactagc caggtggggg cctttccctt tggatggggg 2160 gcatatccga cagttattct ctccaagtgg agacttacgg acagcatata attctccctg 2220 caaggatgta tgataatatg tacaaagtaa ttccaactga ggaagctcac ctgatcctta 2280 gtgtccaggg tttttactgg gggtctgtag gacgagtatg gagtacttga ataattgacc 2340 tgaagtcctc agacctgagg ttccctagag ttcaaacaga tacagcatgg tccagagtcc 2400 aaaacaggga cagatgtaca ttcatcacaa atcccatctt tagcatgaag ggtctggcat 2460 ggcccaaggc cccaagtata tcaaggcact tgggcagaac atgccaagga atcaaatgtc 2520 atctcccagg agttattcaa gggtgag ccc tttacttggg atgtacaggc tttgagcagt 2580 gcagggctgc tgagtcaacc ttttattgta gggaaaggga caggggatga gaggatgagg 2640 aagcccccct ggggatttgg tttggtcttg tgatcaggtg gtctatgggg ctatccctac 2700 aaagaagaat ccagaaatag gggcacattg aggaatgata agagcattca ctgagcccaa 2760 atcattgttt tatttgcctt cttttcacac cattggtgag ggagggatta ccaccctggg 2820 tggttgaaca gttatgaaga ccccacacat agcaccggag atatgagatc aacagtttct 2880 tagccataga gattcacagc ccagagcagg aggacgctgc acaccatgca ggatgacatg 2940 ggggatgcgc tcgggattgg tgtgaagaag caaggactgt tagaggcagg ctttatagta 3000 acaagacggt ggggcaaact ctaatttccg tgggggaatg tcatggtctt gctttactaa 3060 gttttgagac tggcaggtag tgaaactcar taggctgaga atgcagctga accttgtgga 3120 cccagctgat agaggaagta gccaggtggg agcctttccc agtgggtgtg ggacatatct 3180 ggcaagattt tgtggcactc ctggttacag atactggggc agcaaataaa actgaatctt 3240 gttttcagac cttaaaaaaa aaaaaaaaaa aaaagtttt 3279 <; 210 > 383 < 211 > 155 < 212 > PRT < < 221133 > > HHoommoo sapiens F
< 400 > 383 Met Ala Gly Val Arg Asp Gln Gly Gln Gly Ala Arg Trp Pro His Thr May 10 15 Gly Lys Arg Gly Pro Leu Leu Gln Gly Leu Thr Trp Ala Thr Gly Gly 20 25 30 His Cys Phe Ser Ser Glu Glu Ser Gly Ala Val Asp Gly Ala Gly Gln 35 40 45 Lys Lys Asp Arg Ala Trp Leu Arg Cys Pro Glu Ala Val Ala Gly Phe 50 55 60 Pro Leu Gly Ser Asp Cys Arg Glu Gly Gly Arg Gln Gly Cys Gly Gly 65 70 75 80 Ser Asp Asp Glu Asp Asp Leu Gly Val Ala Pro Gly Leu Ala Pro Wing 85 90 95 F
Trp Ala Leu Thr Gln Pro Pro Ser Gln Ser Pro Gly Pro Gln Ser Leu 100 105 110 Pro Ser Thr Pro Ser Ser He Trp Pro Gln Trp Val He Leu He Thr 115 120 125 Glu Leu Thr He Pro Ser Pro Ala His Gly Pro Pro Trp Leu Pro Asn 130 135 140 Ala Leu Glu Arg Gly His Leu Val Arg Glu 145 150 < 210 > 384 < 211 > 557 < 212 > DNA < 213 > Homo sapiens < 400 > 384 ggatcctcta gagcggccgc ctactactac taaattcgcg gccgcgtcga cgaagaagag 60 aaagatgtgt tttgttttgg actctctgtg gtcccttcca atgctgtggg tttccaacca 120 ggggaagggt cccttttgca ttgccaagtg ccataaccat gagcactact ctaccatggt 180 tctgcctcct ggccaagcag gctggtttgc aagaatgaaa tgaatgattc tacagctagg 240 acttaacctt gaaatggaaa gtcttgcaat cccatttgca ggatccgtct gtgcacatgc 300 ctctgtagag agcagcattc ccagggacct tggaaacagt tggcactgta aggtgcttgc 360 acatcctaaa tccccaagac atggtgaaaa aggtgttgta cgtcttcctt ctttattgcc 420 ccttcttatt tatgtgaaca actgtttgtc tttttttgta tcttttttaa actgtaaagt 480 tcaattgtga aaatgaatat aattatgcga catgcaaata tttttttttc aaagtaaaaa aaaaaaaaaa aaaaaaa 540 557
< 210 > 385 < 211 > 337 < 212 > DNA < 213 > Homo sapiens < 400 > 385 ttcccaggtg atgtgcgagg gaagacacat ttactatcct tgatggggct gattccttta 60 gtttctctag cagcagatgg gttaggagga agtgacccaa gtggttgact cctatgtgca 120 tctcaaagcc atctgctgtc ttcaagtacg gacacatcat cactcctgca ttgttgatca 180 aaacgtggag gtgcttttcc tcagctaaga agcccttagc aaaagctcga atagacrtag 240 tatcagacag gtccagtttc cgcaccaaca cctgctggtt ccctgtcgtg gtctggatct 300 ctttggccac caattccccc ttttccacat cccggca 337
< 210 > 386 < 211 > 300 < 212 > DNA < 213 > Homo sapiens < 400 > 386 gggcccgcta ccggcccagg ccccgcctcg cgagtcctcc tccccgggtg cctgcccgca 60 gcccgctcgg cccagagggt gggcgcgggg ctgcctctac cagctggcgg ctgtaactca 120 gcgaccttgg cccgaaggct ctagcaagga cccaccgacc ccagccgcgg cggcggcggc 180 gcggactttg cccggtgtgt ggggcggagc ggactgcgtg tccgcggacg ggcagcgaag 240 atgttagcct tcgctgccag gaccgtggac cgatcccagg gctgtggtgt aacctcagcc 300
< 210 > 387 < 211 > 537 < 212 > DNA < 213 > Homo sapiens < 400 > 387 gggccgagtc gggcaccaag ggactctttg caggcttcct tcctcggatc atcaaggctg 60 ccccctcctg tgccatcatg atcagcacct atgagttcgg caaaagcttc ttccagaggc 120 tgaaccagga ccggcttctg ggcggctgaa aggggcaagg aggcaaggac cccgtctctc 180 ccacggatgg ggagagggca ggaggagacc cagccaagtg ccttttcctc agcactgagg 240 gagggggctt gtttcccttc cctcccggcg acaagctcca gggcagggct gtccctctgg 300 gcggcccagc acttcctcag acacaacttc ttcctgctgc tccagtcgtg gggatcatca 360 cttacccacc ccccaagttc aagaccaaat cttccagctg cccccttcgt gtttccctgt 420 gtttgctgta gctgggcatg tctccaggaa ccaagaagcc ctcagcctgg tgtagtctcc 480 ctgacccttg ttaattcctt aagtctaaag atgatgaact tcaaaaaaaa aaaaaaa 537
< 210 > 388 < 211 > 520 < 212 > DNA < 213 > Homo sapiens < 400 > 388 aggataattt ttaaaccaat caaatgaaaa aaacaaacaa acaaaaaagg aaatgtcatg 60 ccagtttgca tgaggttaaa ttcccctaat gtggaaaaag taagaggact actcagcact 120 gtttgaagat tgcctcttct acagcttctg agaattgtgt tatttcactt gccaagtgaa 180 ggaccccctc cccaacatgc cccagcccac ccctaagcat ggtcccttgt caccaggcaa 240 ccaggaaact gctacttgtg gacctcacca gagaccagga gggtttggtt agctcacagg 300 ccccagaaga acttccccca ttagcatccc atactagact catactcaac tcaactaggc 360 ttgatggtta tcatactcaa ttagacaatt ccatttcttt ctggttatta taaacagaaa 420 atctttcctc ttctcattac cagtaaaggc tcttggtatc tttctgttgg aatgatttct 480 atgaacttgt cttattttaa tggtgggttt tttttctggt 520 < 210 > 389 < 211 > 365 < 212 > DNA < 213 > Homo sapiens < 400 > 389 cgttgcccca gtttgacaga aggaaaggcg gagcttattc aaagtctaga gggagtggag 60 gagttaaggc tggatttcag atctgcctgg ttccaaccgc agtgtgccct ctgctccccc 120 aacgactttc caaataatct caccagcgcc ttccagctca ggcgtcctag aagcgtcttg 180 aagcctatgg ccagctgtct ttgtgttccc tctcacccgc ctgtcctcac agctgagact 240 cccaggaaac cttcagacta ccttcctctg ccttcagcaa ggggcgttgc ccacattctc 300 tgagggtcag tggaagaacc tagactccca ttgctagagg tagaaagggg aagggtgctg 360 365 <gggag; 210 > 390 < 211 > 221 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (221) < 223 > n = A, T, C or G < 400 > 390 tgcctctcca tcctggcccc gacttctctg tcaggaaagt ggggatggac cccatctgca 60 tacacggntt ctcatgggtg tggaacatct ctgcttgcgg tttcaggaag gcctctggct 120 gctctangag tctgancnga ntcgttgccc cantntgaca naaggaaagg cggagcttat 180 tcaaagtcta gagggagtgg aggagttaag gctggatttc a 221 < 210 > 391 < 211 > 325 F < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (325) < 223 > n = A, T, C or G < 400 > 391 tggagcaggt cccgaggcct ccctagagcc tggggccgac tctgtgncga tgcangcttt 60 ctctcgcgcc cagcctggag ctgctcctgg catctaccaa caatcagncg aggcgagcag 120 tagccagggc actgctgcca acagccagtc cnnataccat catgtnaccc ggtgngctct 180 naanttngat ntccanagcc ctacccatcn tagttctgct ctcccaccgg ntaccagccc 240 gaatcctaca cactgcccag gccagtaccc tgtcccgacg tctctaccta ccagtacgat 300 gagacctccg gctactacta CTGA 325 < 210 > 392 < 211 > 277 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (277) < 223 > n = A, T, C or G < 400 > 392 atattgttta actccttcct ttatatcttt taacattttc atggngaaag gttcacatct 60 agtctcactt nggcnagngn ctcctacttg agtctcttcc ccggcctgnn ccagtngnaa 120 antaccanga accgncatgn cttaanaacn ncctggtttn tgggttnntc aatgactgca 180 tgcagtgcac caccctgtcc actacgtgat gctgtaggat taaagtctca cagtgggcgg 240 ctgaggatac agcgccgcgt cctgtgttgc tggggaa 277 < 210 > 393 < 211 > 566 < 21"2> DNA <213> Homo sapiens F
< 400 > 393 actagtccag tgtggtggaa ttcgcggccg cgtcgacggacaggtcagct gtctggctca 60 gtgatctaca ttctgaagtt gtctgaaaat gtcttcatga ttaaattcag cctaaacgtt 120 cactgcagag ttgccgggaa gagtttccaa acaatgctgt tctgcgggca ccttagccca 180 gagaaggtct agtttgtcca tcagcattat catgatatca ggactggtta cttggttaag 240 ggagatctgt gaggggtcta cccttttaga gacaccttac gtatttggga ttataatgaa 300 gggtggtttt caaaagtaga aatgtcctgt attccgatga tcatcctgta aacattttat 360 catttattaa tcatccctgc ctgtgtctat tattatattcatatctctac gctggaaact 420 ttctgcctca atgtttactg tgcctttgtt tttgctagtt tgtgttgttg aaaaaaaaaa 480 cattctctgc ctgagtttta atttttgtcc aaagttattt taatctatac aattaaaagc 540 ttttgcctat caaaaaaaaaaaaaa 566 < 210 > 394 < 211 > 384 < 212 > DNA < 213 > Homo sapiens < 220 > F
< 221 > diverse feature < 222 > (1) ... (384) < 223 > n = A, T, C or G < 400 > 394 gaacatacat gtcccggcac ctgagctgca gtctgacatc atcgccatca cgggcctcgc 60 tgcaaattng gaccgggcca aggctggact gctggagcgt gtgaaggagc tacaggccna 120 gcaggaggac cgggctttaa ggagttttaa gctgagtgtc actgtagacc ccaaatacca 180 tcccaagatt atcgggagaa agggggcagt aattacccaa atccggttgg agcatgacgt 240 gaacatccag tttcctgata aggacgatgg gaaccagccc caggaccaaa ttaccatcac 300 agggtacgaa aagaacacag aagctgccag ggatgctata ctgagaattg tgggtaaact 360 tgagcagatg gtttctgagg ACGT 384 < 210 > 395 < 211 > 399 < 212 > DNA < 213 > Homo sapiens < 400 > 395 ggcaaaactg tgtgacctca ataagacctc gcagatccaa ggtcaagtat cagaagtgac 60 tctgaccttg gactccaaga cctacatcaa cagcctggct atattagatg atgagccagt 120 tatcagaggt ttcatcattg cggaaattgt ggagtctaag gaaatcatgg cctctgaagt 180 attcacgtct ttccagtacc ctgagttctc tatagagttg cctaacacag gcagaattgg 240 ccagctactt gtctgcaatt gtatcttcaa gaataccctg gccatccctt tgactgacgt 300 caagttctct ttggaaagcc tgggcatctc ctcactacag acctctgacc atgggacggt 360 gcagcctggt gagaccatcc aatcccaaat aaaatgcac 399 < 210 > 396 < 211 > 403 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (403) < 223 > n = A, T, C or G < 400 > 396 tggagttntc agtgcaaaca agccataaag cttcagtagc aaattactgt ctcacagaaa 60 F gacattttca acttctgctc cagctgctga taaaacaaat catgtgttta gcttgactcc 120 agacaaggac aacctgttcc ttcataactc tctagagaaa aaaaggagtt gttagtagat 180 actaaaaaaa gtggatgaat aatctggata tttttcctaa aaagattcct tgaaacacat 240 taggaaaatg gagggcctta tgatcagaat gctagaatta gtccattgtg ctgaagcagg 300 gtttagggga gggagtgagg gataaaagaa ggaaaaaaag aagagtgaga aaacctattt 360 atcaaagcag gtgctatcac tcaatgttag gccctgctct ttt 403 < 210 > 397 < 211 > 100 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (100) < 223 > n = A, T, C or G < 400 > 397 actagtncag tgtggtggaa ttcgcggccg cgtcgaccta naanccatct ctatagcaaa 60 tccatccccg ctcctggttg gtnacagaat gactgacaaa 100 < 210 > 398 < 211 > 278 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (278) < 223 > n = A, T, C or G < 400 > 398 F gcggccgcgt cgacagcagt tccgccagcg ctcgcccctg ggtggggatg tgctgcacgc 60 ccacctggac atctggaagt cagcggcctg gatgaaagag cggacttcac ctggggcgat 120 tcactactgt gcctcgacca gtgaggagag ctggaccgac agcgaggtgg actcatcatg 180 ctccgggcag cccatccacc tgtggcagtt cctcaaggag ttgctactca agccccacag 240 ctatggccgc ttcattangt ggctcaacaa ggagaagg 278 < 210 > 399 < 211 > 298 < 212 > DNA < 21 3 > Homo sapiens < 220 > < 221 > Diverse Characteristics < 222 > ( 1 ) . . . (298) < 223 > n = A, T, C or G < 400 > 399 acggaggtgg aggaagcgnc cctgggatcg anaggatggg tcctgncatt gaccncctcn 60 ggggtgccng catggagcgc atgggcgcgg gcctgggcca cggcatggat cgcgtgggct 120 ccgagatcga gcgcatgggc ctggtcatgg accgcatggg ctccgtggag cgcatgggct 180 ccggcattga gcgcatgggc ccgctgggcc tcgaccacat ggcctccanc attgancgca 240 tgggccagac catggagcgc attggctctg gcgtggagcn catgggtgcc ggcatggg 298 < 210 > 400 F < 211 > 548 < 212 > DNA <; 213 > Homo sapiens < 400 > 400 acatcaacta cttcctcatt ttaaggtatg gcagttccct tcatcccctt ttcctgcctt 60 gtacatgtac atgtatgaaa tttccttctc ttaccgaact ctctccacac atcacaaggt 120 cacgcttaga caaagaacca agggtaagag ggcaccctat gaaatgaaat ggtgatttct 180 tgagtctctt ttttccacgt ttaaggggcc atggcaggac ttagagttgc gagttaagac 240 tgcagagggc tagagaatta tttcatacag gctttgaggc cacccatgtc acttatcccg 300 tataccctct caccatcccc ttgtctactc tgatgccccc aagatgcaac tgggcagcta 360 gttggcccca taattctggg cctttgttgt ttgttttaat tacttgggca tcccaggaag 420 ctttccagtg atctcctacc atgggccccc ctcctgggat caagcccctc ccaggccctg 480 tccccagccc ctcctgcccc agcccacccg cttgccttgg tgctcagccc tc cattggg 540 agcaggtt 548 < 210 > 401 < 211 > 355 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (355) < 223 > n = A, T, C or G < 400 > 401 actgtttcca tgttatgttt ctacacattg ctacctcagt gctcctggaa acttagcttt 60 tgatgtctcc aagtagtcca ccttcattta actctttgaa actgtatcat ctttgccaag 120 taagagtggt ggcctatttc agctgctttg acaaaatgac tggctcctga cttaacgttc 180 tataaatgaa tgtgctgaag caaagtgccc atggtggcgg cgaagaagan aaagatgtgt 240 tttgttttgg actctctgtg gtcccttcca atgctgnggg tttccaacca ggggaagggt 300 cccttttgca ttgccaagtg ccataaccat gagcactact ctaccatggn tctgc 355 F
< 210 > 402 < 211 > 407 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (407) < 223 > n = A, T, C or G < 400 > 402 atggggcaag ctggataaag aaccaagacc cactggagta tgctgtcttc aagaaaccca 60 tctcacatgc ggtggcatac ataggctcaa aataaaggaa tggagaaaaa tatttcaagc 120 aaatggaaaa cagaaaaaag caggtgttgc actcctactt tctgacaaaa cagactatgc 180 gaataaagat aaaaaagaga aggacattac aaaggtggtc ctgacctttg ataaatctca 240 ttgcttgata ccaacctggg ctgttttaat tgcccaaacc aaaaggataa tttgctgagg 300 ttgtggagct tctcccctgc agagagtccc tgatctccca aaatttggtt gagatgtaag 360 gntgattttg ctgacaactc gttttactca cttttctgaa tttccaa 407 < 210 > 403 < 21-1 > 303 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (303) < 223 > n = A, T, C or G < 400 > 403 cagtatttat agccnaactg aaaagctagt agcaggcaag tctcaaatcc aggcaccaaa 60 gagccatggc tcctaagcaa atggtgaaaa tgcaaaagga gagtctggcc aatctacaaa 120 gacctactca tagagaacaa gtcatgaaca aaaaggcaga caccaacatg gatctcatgg 180 gggattggat attgtaatta tagagcagga agatgacagt tggcacaaca gatcgtcatt 240 tcttaacaac gaccgaaacc cattatttac ataaacctcc attcggtaac catgttgaaa 300 gga 303 < 210 > 404 < 211 > 225 < 212 > DNA < 213 > Homo sapiens F
< 400 > 404 aagtgtaact tttaaaaatt tagtggattt tgaaaattct tagaggaaag taaaggaaaa 60 attgttaatg cactcattta cctttacatg gtgaaagttc tctcttgatc ctacaaacag 120 acattttcca ctcgtgtttc catagttgtt aagtgtatca gatgtgttgg gcatgtgaat 180 ctccaagtgc ctgtgtaata aataaagtat ctttatttca ttcat 225 < 210 > 405 < 211 > 334 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (334) F < 223 > n = A, T, C or G < 400 > 405 gagctgttat actgtgagtt ctactaggaa atcatcaaat ctgagggttg tctggaggac 60 ttcaatacac ctccccccat agtgaatcag cttccagggg gtccagtccc tctccttact 120 tcatccccat cccatgccaa aggaagaccc tccctccttg gctcacagcc ttctctaggc 180 ttcccagtgc ctccaggaca gagtgggtta tgttttcagc tccatccttg ctgtgagtgt 240 tgtgcctcca ctggtacggt gcttctgctc agtgcttcat ggacagtgtc cagcccatgt 300 cactctccac tctctcanng tggatcccac CCCT 334
< 210 > 406 < 211 > 216 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (216) < 223 > n = A, T, C or G < 400 > 406 tttcatacct aatgagggag ttganatnac atnnaaccag gaaatgcatg gatctcaang 60 gaaacaaaca cccaataaac tcggagtggc agactgacaa ctgtgagaca tgcacttgct 120 acnaaacaca aatttnatgt tgcacccttg tttctacacc tgtgggttat gacaaagaca 180 actgccaaag aatnttcaag aaggaggact gccant 216
< 210 > 407 < 211 > 413 < 212 > DNA < 213 > Homo sapiens < 400 > 407 gctgacttgc tagtatcatc tgcattcatt gaagcacaag aacttcatgc cttgactcat 60 gtaaatgcaa taggattaaa aaataaattt gatatcacat ggaaacagac aaaaaatatt 120 gtacaacatt gcacccagtg tcagattcta cacctggcca ctcaggaagc aagagttaat 180 cccagaggtc tatgtcctaa tgtgttatgg caaatggatg tcatgcacgt accttcattt 240 ggaaaattgt catttgtcca tgtgacagtt gatacttatt cacatttcat atgggcaacc 300 tgccagacag gagaaagtct tcccatgtta aaagacattt attatcttgt tttcctgtca 360 tgggagttcc agaaaaagtt aaaacagaca atgggccagg ttctgtagta aag 413
< 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (183) < 223 > n = A, T, C or G < 400 > 408 ggagctngcc ctcaattcct ccatntctat gttancatat ttaatgtctt ttgnnattaa 60 tncttaacta gttaatcctt aaagggctan ntaatcctta actagtccct ccattgtgag 120 cattatcctt ccagtattcn ccttctnttt tatttactcc ttcctggcta cccatgtact 180 409 < 211 > 250 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (250) < 223 > n = A, T, C or G < 400 > 409 cccacgcatg ataagctctt tatttctgta agtcctgcta ggaaatcatc aaatctgacg 60 gtggtttggg ggacctgaac aaacctcctg taattaatca gctttcagtt tctcccccta 120 gtccctcctt caacaacata ggaggatcct ccccttcttt ctgctcacgg ccttatctag 180 gcccccagga gcttcccagt tatgtttaca cagcgtgggc gcgcntcctt gctggggggg ggccntatgc 240 250 < 210 > 410 < 211 > 306 < 212 > DNA < 2T3 > Homo sapiens < 220 > F
< 221 > diverse feature < 222 > (1) ... (306) < 223 > n = A, T, C or G < 400 > 410 ggctggtttg caagaatgaa atgaatgatt ctacagctag gacttaacct tgaaatggaa 60 agtcttgcaa tcccatttgc aggatccgtc tgtgcacatg cctctgtaga gagcagcatt 120 cccagggacc ttggaaacag ttggcactgt aaggtgcttg ctccccaaga cacatcctaa 180 aaggtgttgt aatggtgaaa accgcttcct tctttattgc cccttcttat ttatgtgaac 240 nactggttgg ctttttttgn atctttttta aactggaaag ttcaattgng aaaatgaata tcntgc 300 306 < 210 > 411 < 211 > 261 < 212 > DNA < 213 > Homo sapiens < 220 > F
< 221 > diverse feature < 222 > ( 1 ) . . . (261) < 223 > n = A, T, C or G < 400 > 411 cttaggtnaa agagatattn gttcccatga agttcataga tggccacaca actatatgac 60 ggatcttttg tatttaagga ttctgagatt ttgcttgagc aggattagat aaggctgttc 120 tgaaatggaa tttaaatgtc cagatttcaa aaaaaaaccc ggtgggaaca cacaatctag 180 aggaaggaaa gatgtgaata ggctgatggg caaaaaacca atttacccat cagttccagc ggngaggcaa cttctctcaa 240 to 261 < 210 > 412 < 211 > 241 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (241) < 223 > n = A, T, C or G < 400 > 412 gttcaatgtt acctgacatt tctacaacac cccactcacc gatgtattcg ttgcccagtg 60 ggaacatacc agcctgaatt tggaaaaaat aattgtgttt cttgcccagg aaatactacg 120 actgactttg atggctccac aaacataacc cagtgtaaaa acagaagatg tggaggggag 180 ctggaagatt tcactgggta cattgaattc ccaaactacc cangcaatta cccagccaac 240"241 < 210 > 413 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (231) < 223 > n = A, T, C, or G < 400 > 413 atccaagtga aactcttaca ctcatctgtg tgcttgaatc ctttccactg tctcatctcc 60 ctcatccaag tttctagtac cttctctttg ttgtgaagga taatcaaact gaacaacaaa 120 aagtttactc tcctcatttg gaacctaaaa actctcttct tcctgggtct gagggctcca 180 agaatccttg aatcanttct cagatcattg gggacaccan atcaggaacc t 231 < 210 > 414 < 211 > 234 < 212 > DNA < 213 > Homo sapiens < 400 > 414 actgtccatg aagcactgag cagaagctgg aggcacaacg caccagacac tcacagcaag 60 gatggagctg aaaacataac ccactc tgtc ctggaggcac tgggaagcct agagaaggct 120 gtgagccaag gagggagggt cttcctttgg catgggatgg ggatgaagta aggagaggga 180 ctggaccccc tggaagctga ttcactatgg ggggaggtgt attgaagtcc teca 234 < 210 > 415 F < 211 > 217 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (217) < 223 > n = A, T, C or G < 400 > 415 gcataggatt aagactgagt atcttttcta cattctttta actttctaag gggcacttct 60 caaaacacag accaggtagc aaatctccac tgctctaagg ntctcaccac cactttctca 120 cacctagcaa tagtagaatt cagtcctact tctgaggcca gaagaatggt tcagaaaaat 180 antggattat aaaaaataac aattaagaaa aataatc 217 < 210 > 416 < 211 > 213 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (213) < 223 > n = A, T, C or G < 400 > 416 atgcatatnt aaagganact gcctcgcttt tagaagacat ctggnctgct ctctgcatga 60 ggcacagcag taaagctctt tgattcccag aatcaagaac tctccccttc agactattac 120 cgaatgcaag gtggttaatt gaaggccact aattgatgct caaatagaag gatattgact 180 atattggaac agatggagtc tctactacaa aag 213 < 210 > 417 < 211 > 303 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature F < 222 > (1) ... (303) < 223 > n = A, T, C or G < 400 > 417 nagtcttcag gcccatcagg gaagttcaca gtcatacata ctggagagaa tgtactgtat 60 gtgggaaagg ctttactctg agttcaaatc ttcaagccca tcagagagtc cacactggag 120 agaagccata caaatgcaat gagtgtggga agagcttcag gagggattcc cattatcaag 180 ttcatctagt ggtccacaca ggagagaaac cctataaatg tgagatatgt gggaagggct 240 tcantcaaag ttcgtatctt ngaaggncca caaatccatc cagtatanan aaacctttta 300 agt 303 < 210 > 418 < 211 > 328 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature F < 222 > (1) ... (328) < 223 > n = A, T, C or G < 400 > 418 tttttggcgg tggtggggca gggacgggac angagtctca ctctgttgcc caggctggag 60 tgcacaggca tgatctcggc tcactacaac ccctgcctcc catgtccaag cgattcttgt 120 gcctcagcct tccctgtagc tagaattaca ggcacatgcc accacaccca gctagttttt 180 gtatttttag tagagacagg gtttcaccat gttggccagg ctggtctcaa actcctnacc 240 ggctggtctc tcagnggtca aaactcctga cctcaagtga tctgcccacc tcagcctccc 300 aaagtgctan gattacaggc 328 <cgtgagcc; 210 > 419 < 211 > 389 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (389) < 223 > n = A, T, C or G < 400 > 419 cctcctcaag acggcctgtg gtccgcctcc cggcaaccaa gaagcctgca gtgccatatg 60 acccctgagc catggactgg agcctgaaag gcagcgtaca ccctgctcct gatcttgctg 120 cttgtttcct ctctgtggct ccattcatag cacagttgtt gcactgaggc ttgtgcaggc 180 cgagcaaggc caagctggct caaagagcaa ccagtcaact ctgccacggt gtgccaggca 240 ccggttctcc agccaccaac ctcactcgct cccgcaaatg gcacatcagt tcttctaccc 300
F taaaggtagg accaaagggc atctgctttt ctgaagtcct ctgctctatc agccatcacg 360 389 tggcagccac tcnggctgtg tcgacgcgg
< 210 > 420 < 211 > 408 < 212 > DNA < 213 > Homo sapiens 15 < 400 > 420 gttcctccta actcctgcca gaaacagctc tcctcaacat gagagctgca cccctcctcc 60 tggccagggc agcaagcctt agccttggct tcttgtttct gctttttttc tggctagacc 120 gaagtgtact agccaaggag ttgaagtttg tgactttggt gtttcggcat ggagaccgaa 180
gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 240 gccaactcac ccagctgggc atggagcagc attatgaact tggagagtat ataagaaaga 300 gatatagaaa attcttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 360 acgttgaccg gactttgatg aagtgctatg acaaacctgg caagcccg 408
F 25 < 210 > 421 < 211 > 352 < 212 > DNA < 213 > Homo sapiens 30 < 220 > < 221 > diverse feature < 222 > (1) ... (352) < 223 > n = A, T, C or G 35 < 400 > 421 gctcaaaaat ctttttactg atnggcatgg ctacacaatc attgactatt acggaggcca 60 gaggagaatg aggcctggcc tgggagccct gtgcctacta naagcacatt agattatcca 120 ttcactgaca gaacaggtct tttttgggtc cttcttctcc accacnatat acttgcagtc 180 ctccttcttg aagattcttt ggcagttgtc tttgtcataa cccacaggtg tagaaacaag 240
40 ggtgcaacat gaaatttctg tttcgtagca agtgcatgtc tcacaagttg gcangtctgc 300 cactccgagt ttattgggtg tttgtttcct ttgagatcca tgcatttcct gg 352
< 210 > 422 < 211 > 337 45 < 212 > DNA < 213 > Homo sapiens < 400 > 422 atgccaccat gctggcaatg cagcgggcgg tcgaaggcct gcatatccag cccaagctgg 60 50 cgatgatcga cggcaaccgt tgcccgaagt tgccgatgcc agccgaagcg gtggtcaagg 120 gcgatagcaa ggtgccggcg atcgcggcgg cgtcaatcct ggccaaggtc agccgtgatc 180 gtgaaatggc agctgtcgaa ttgatctacc cgggttatgg catcggcagg cataagggct 240 atccgacacc ggtgcacctg gaagccttgc agcggctggg gccgacgccg attcaccgac 300 gcttcttccg ccggtacggc tggcctatga aaattat 337
: < 210 > 423 < 211 > 310 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature
gctcaaaaat ctttttactg atatggcatg gctacacaat cattgactat tagaggccag 60
aggagaatga ggcctggcct gggagccctg tgcctactan aagcncatta gattatccat 120 tcactgacag aacaggtctt ttttgggtcc ttcttctcca ccacgatata cttgcagtcc 180 tccttcttga agattctttg gcagttgtct ttgtcataac ccacaggtgt anaaacaagg 240 gtgcaacatg aaatttctgt ttcgtagcaa gtgcatgtct cacagttgtc aagtctgccc 300 tccgagttta 310
< 210 > 424 < 211 > 370 < 212 > DNA < 213 > Homo sapiens 20 < 220 > F < 221 > diverse feature < 222 > (1) ... (370) < 223 > n = A, T, C or G 25 < 400 > 424 gctcaaaaat ctttttactg ataggcatgg ctacacaatc attgactatt agaggccaga 60 ggagaatgag gcctggcctg ggagccctgt gcctactaga agcacattag attatccatt 120 cactgacaga acaggtcttt tttgggtcct tcttctccac cacgatatac ttgcagtcct 180
ccttcttgaa gattctttgg cagttgtctt tgtcataacc cacaggtgta gaaacatcct 240 ggttgaatct cctggaactc cctcattagg tatgaaatag catgatgcat tgcataaagt 300 cacgaaggtg gcaaagatca caacgctgcc cagganaaca ttcattgtga taagcaggac 360 tccgtcgacg 370
< 210 > 425 < 211 > 216 < 212 > DNA < 213 > Homo sapiens 40 < 220 > < 221 > diverse feature < 222 > (1) ... (216) < 223 > n = A, T, C or G 45 < 400 > 425 aattgctatn ntttattttg ccactcaaaa taattaccaa aaaaaaaaaa tnttaaatga 60 taacaacnca acatcaaggn aaananaaca ggaatggntg accntgcata aatnggccga 120 anattatcca ttatnttaag ggttgacttc aggntacagc acacagacaa acatgcccag 180 gaggntntca ggaccgctcg atgtnttntg aggagg 216
50 < 210 > 426 < 211 > 596 < 212 > DNA < 213 > Homo sapiens 53 < 400 > 426 cttccagtga ggataaccct gttgccccgg gccgaggttc tccattaggc tctgattgat 60 tggcagtcag tgatggaagg gtgttctgat cattccgact gccccaaggg tcgctggcca 120 gctctctgtt ttgctgagtt ggcagtagga cctaatttgt taattaagag tagatggtga 180 gctgtccttg tattttgatt aacctaatgg ccttcccagc ttcagctgga acgactcgga 240 caacttttaa gacatcacgg tgaaatgatt tgaagggcca ttaagaggca cttcccgtta 300 ttaggcagtt catctgcact gataacttct tggcagctga gctggtcgga gctgtggccc 360 aaacgcacac ttggcttttg gttttgagat acaactctta atcttttagt catgcttgag 420 ggtggatggc cttttcagct ttaacccaat ttgcactgcc ttggaagtgt agccaggaga 480 atacactcat atactcgtgg gcttagaggc cacagcagat gtcattggtc tactgcctga 540 gtcccgctgg tcccatccca ggaccttcca tcggcgagta cctgggagcc cgtgct 596
< 210 > 427 < 211 > 107 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (107) < 223 > n = A, T, C or G < 400 > 427 gaagaattca agttaggttt attcaaaggg cttacngaga atcctanacc caggncccag 60 cccgggagca gccttanaga gctcctgttt gactgcccgg ctcagng 107
< 210 > 428 < 211 > 38 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > ( 1 ) . . . (38) < 223 > n = A, T, C or G < 400 > 428 gaacttccna anaangactt tattcactat tttacatt < 210 > 429 < 211 > 544 < 212 > DNA < 213 > Homo sapiens < 400 > 429 cggaataaaa ctttgctgga gtggacgcaa gcatgacctc ctgatgaggg cgctgcattt 60 attgaagagc ggctgcagcc ctgcggttca gattaaaatc cgagaattgt atagacgccg 120 actcttgaag atatccacga gactttctga tttatecaca atcaaatcat cggttttcag 180 tttggatggt ggctcatcac ctgtagaacc tgacttggcc gtggctggaa tccactcgtt 240 gccttccact tcagttacac ctcactcacc atcctctcct gttggttctg tgctgcttca 300 agatactaag cccacatttg agatgcagca gccatctccc ccaattcctc ctgtccatcc 360 tgatgtgcag ttaaaaaatc tgccctttta tgatgtcctt gatgttctca tcaagcccac 420 gagtttagtt caaagcagta ttcagcgatt tcaagagaag ttttttattt ttgctttgac 480 acctcaacaa gttagagaga tatgcatatc cagggatttt ttgccaggtg gtaggagaga 540 ttat 544
< 2I0 > 430 < 211 > 507 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (507) < 223 > n = A, T, C or G < 400 > 430 cttatcncaa tggggctccc aaacttggct gtgcagtgga aactccgggg gaattttgaa 60 gaacactgac acccatcttc ctctgattta caccccgaca agtgagaaca attgggctgc 120 gagcatcaat ttaaaaagct gcccagaatg ttntcctggg cagcgttgtg atctttgccn 180 ccttcgtgac tttatgcaat gcatcatgct atttcatacc taatgaggga gttccaggag 240 attcaaccag gatgtttcta cncctgtggg ttatgacaaa gacaactgcc aaagaatntt 300 caagaaggag gactgcaagt atatcgtggt ggagaagaag gacccaaaaa agacctgttc 360 tgtcagtgaa tggataatct aatgtgcttc tagtaggcac agggctccca ggccaggcct 420 cattctcctc tggcctctaa tagtcaatga ttgtgtagcc atgcctatca gtaaaaagat 480 ttttgagcaa aaaaaaaaaa aaaaaaa 507 < 210 > 431 < 211 > 392 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (392) < 223 > n = A, T, C or G < 400 > 431 aatggataaa gaaaattcag aacaaatgaa gtacaaaata tttcagattt acatagcgat 60 gcacttatca aaacaagaaa ggaggactta caaatggaag tacactctan aaccatcatc 120 tatcatggct aaatgtgaga ttagcacagc tgtattattt gtacattgca aacacctaga 180 aagagatggg aaacaaaatc ccaggagttt tgtgtgtgga gtcctgggtt ttccaacaga 240 gcattctgag catcattcca ttggggatca attagggnga ttctggagtt ggaatgttca 300 acaaaagtga tgttgttagg taaaatgtac aacttctgga tctatgcaga cattgaaggt 360 392 ct gcaatgagtc tggcttttac tctgctgttt
< 210 > 432 < 211 > 387 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (387) < 223 > n = A, T, C or G < 400 > 432 cataatcaaa ggtatccnta tatagctgta gtacatgttt tcattggngt agattaccac 60 aaatgcaagg caacatgtgt agatctcttg tcttattctt ttgtctataa tactgtattg 120 gctctcggna ngtagtccaa gtccagccac tgngaaacat gctcccttta gattaacctc 180 gtggacnctn ttgttgnatt gtctgaactg tagngccctg tattttgctt ctgtctgnga 240 ttctggggca attctgttgc tttccttgng atgcagagga ccaccacaca gatgacagca 300 atctgaattg ntccaatcac agctgcgatt aagacatact gaaatcgtac aggaccggga 360 gaacactgga acaacgtata gtccttt 387 < 210 > 433 < 211 > 281 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (281) < 223 > n = A, T, C or G < 400 > 433 ttcaactagc anagaanact gcttcagggn gtgtaaaatg aaaggcttcc acgcagttat 60 ctgattaaag aacactaaga gagggacaag gctagaagcc gcaggatgtc tacactatag 120 caggcnctat ttgggttggc tggaggagct gtggaaaaca tggagagatt ggcgctggag 180 atcgccgtgg ctattcctcn ttgntattac accagngagg ntctctgtnt gcccactggt 240 tnnaaaaccg ntatacaata atgatagaat aggacacaca t 281
< 210 > 434 < 211 > 484 < 212 > DNA < 213 > Homo sapiens < 400 > 434 ttttaaaata agcatttagt gctcagtccc tactgagtac tctttctctc ccctcctctg 60 aatttaattc tttcaacttg caatttgcaa ggattacaca tttcactgtg atgtatattg 120 tgttgcaaaa aaaaaaaagt gtctttgttt aaaattactt ggtttgtgaa tccatcttgc 180 tttttcccca ttggaactag tcattaaccc atctctgaac tggtagaaaa acatctgaag 240 agctagtcta tcagcatctg acaggtgaat tggatggttc tcagaaccat ttcacccaga 300 cagcctgttt ctatcctgtt taataaatta gtttgggttc tctacatgca taacaaaccc 360 tgtcacataa tgctccaatc aagtctgtga cttgaagttt agtcagcacc cccaccaaac 420 tttatttttc tatgtgtttt ttgcaacata tgagtgtttt gaaaataaag tacccatgtc 480 ttta 484
< 210 > 435 < 211 > 424 < 212 > DNA < 213 > Homo sapiens < 400 > 435 gagcaggtca gcgccgctca ctttctgcct tccacgtcct ccttcaagga agccccatgt 60 gggtagcttt caatatcgca ggttcttact cctctgcctc tataagctca aacccaccaa 120 cgatcgggca agtaaacccc ctccctcgcc gacttcggaa ctggcgagag ttcagcgcag 180 atgggcctgt ggggaggggg caagatagat gagggggagc ggcatggtgc ggggtgaccc 240 cttggagaga ggaaaaaggc cacaagaggg gctgccaccg ccactaacgg agatggccct 300 ggtagagacc tttgggggtc tggaacctct ggactcccca tgctctaact cccacactct 360 gctatcagaa acttaaactt gaggattttc tctgtttttc actcgcaata aattcagagc 420 aaac 424
< 210 > 436 < 211 > 667 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (667) < 223 > n = A, T, C or G < 400 > 436 accttgggaa nactctcaca atataaaggg tcgtagactt tactccaaat tccaaaaagg 60 tcctggccat gtaatcctga aagttttccc aaggtagcta taaaatcctt ataagggtgc 120 agcctcttct ggaattcctc tgatttcaaa gtctcactct caagttcttg aaaacgaggg 180 cagttcctga aaggcaggta tcttcagaaa tagcaactga gaggaactgt gtgcaccggg 240 atgggctgcc agagtaggat aggattccag atgctgacac cttctggggg aaacagggct 300 gccaggtttg tcatagcact catcaaagtc cggtcaacgt ctgtgcttcg aatataaacc 360 tgttcatgtt tataggactc attcaagaat tttctatatc tctttcttat atactctcca 420 agttcataat gctgctccat gcccagctgg gtgagttggc caaatccttg tggccatgag 480 gattccttta tggggtcagt gggaaaggtg tcaatgggac ttcggtctcc atgccgaaac 540 caaacttcaa accaaagtca ctccttggct agtacacttc ggtctagcca gaaaaaaagc 600 agaaacaaga agccaaggct aaggcttgct gccctgccag gaggaggggt gcagctctca tgttgag 660 667
< 210 > 437 < 211 > 693 < 212 > DNA < 213 > Homo sapiens < 400 > 437 ctacgtctca accctcattt ttaggtaagg aatcttaagt ccaaagatat taagtgactc 60 acacagccag gtaaggaaag ctggattggc acactaggac tctaccatac cgggttttgt 120 taaagctcag gttaggaggc tgataagctt ggaaggaact tcagacagct ttttcagatc 180 ataaaagata attcttagcc catgttcttc tccagagcag acctgaaatg acagcacagc 240 aggtactcct ctattttcac ccctcttgct tctactctct ggcagtcaga cctgtgggag 300 gccatgggag aaagcagctc tctggatgtt tgtacagatc atggactatt ctctgtggac 360 ggttacccta catttctcca ggtgtcacta ttggggggac agccagcatc tttagctttc 420 atttgagttt ctgtctgtct tcagtagagg aaacttttgc tcttcacact tcacatctga 480 acacctaact gctgttgctc ctgaggtggt gaaagacaga tatagagctt acagtattta 540 tcctatttct aggcactgag ggctgtgggg taccttgtgg tgccaaaaca gatcctgttt 600 taaggacatg ttgcttcaga gatgtctgta actatctggg ggctctgttg gctctttacc 660 693 acc ctgcatcatg tgctctcttg gctgaaaatg
< 210 > 438 < 211 > 360 < 212 > DNA < 213 > Homo sapiens < 400 > 438 ctgcttatca caatgaatgt tctcctgggc agcgttgtga tctttgccac cttcgtgact 60 ttatgcaatg catcatgcta tttcatacct aatgagggag ttccaggaga ttcaaccagg 120 atqtttctac acctgtgggt tatgacaaag acaactgcca aagaatcttc aagaaggagg 180 actgcaagta tatctggtgg agaagaagga cccaaaaaag acctgttctg tcagtgaatg -240 tgtgcttcta gataatctaa gtaggcacag ggctcccagg ccaggcctca ttctcctctg 300 gcctctaata gtcaataatt gtgtagccat gcctatcagt aaaaagattt ttgagcaaac 360
< 210 > 439 < 211 > 431 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (431) < 223 > n = A, T, C or G < 400 > 439 actcctgcca gttcctnnta gaaacagctc tcctcaacat gagagctgca cccctcctcc 60 tggccagggc agcaagcctt agccttggct tcttgtttct gctttttttc tggctagacc 120 gaagtgtact agccaaggag ttgaagtttg tgactttggt gtttcggcat ggagaccgaa 180 gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 240 gccaactcac ccagctgggc atggagcagc attatgaact tggagagtat ataagaaaga 300 gatatagaaa attcttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 360 acgttgaccg gactttgatg agtgctatga caaacctggc agcccgtcga cgcggccgcg 420 aatttagtag t 431
< 210 > 440 < 211 > 523 < 212 > DNA < 213 > Homo sapiens < 400 > 440 cttaggtcaa agagataaag gttcccatga agttcataga tggccacaca actatatgac 60 ggatcttttg tatttaagga ttctgagatt ttgcttgagc aggattagat aaggctgttc 120 tgaaatggaa tttaaatgtc cagatttcaa aaaaaaaccc ggtgggaaca cacaatctag 180 aggaaggaaa gatgtgaata ggctgatggg caaaaaacca atttacccat cagttccagc 240 ggagaggcaa cttctctcaa agaaaggaga tacagtggag acatctggaa agttttctcc 300 actggaaaac tgctactatc tgtttttata tttctgttaa aatatatgag gctacagaac 360 taaaaattaa aacctctttg tgtcccttgg tcctggaaca tttatgttcc ttttaaagaa 420 acaaaaatca aactttacag aaagatttga tgtatgtaat acatatagca gctcttgaag 480 tatatatatc atagcaaata agtcatctga tgagaacaag cta 523> 441 < 211 > 430 < 212 > DNA < 213 > Homo sapiens < 400 > 441 actcctgcca gttcctccta gaaacagctc tcctcaacat gagagctgca cccctcctcc 60 tggccagggc agcaagcctt agccttggct tcttgtttct gctttttttc tggctagacc 120 gaagtgtact agccaaggag ttgaagtttg tgactttggt gtttcggcat ggagaccgaa 180 gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 240 gccaactcac ccagctgggc atggagcagc attatgaact tggagagtat ataagaaaga 300 gatatagaaa attcttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 360 acgttgaccg gactttgatg agtgctatga caaacctggc aacccgtcga cgcggccgcg 420 aatttagtag 430
< 210 > 442 < 211 > 362 < 212 > DNA < 213 > Homo sapiens < 400 > 442 ctaaggaatt agtagtgttc ccatcacttg tttggagtgt gctattctaa aagattttga 60 tttcctggaa tgacaattat attttaactt tggtggggga aagagttata ggaccacagt 120 gatacttgta cttcacttct aattaatctt ttattgcact tgttttgacc attaagctat 180 atgtttagaa atggtcattt tacggaaaaa ttagaaaaat tctgataata gtgcagaata 240 aatgaattaa tgttttactt aatttatatt gaactgtcaa tgacaaataa aaattctttt 300 tgattatttt ttgttttcat ttaccagaat aaaaactaag aattaaaagt ttgattacag 360 I 362
210 > 443 211 > 624 212 > DNA 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (624) < 223 > n = A, T, C or G < 400 > 443 tttttttttt gcaacacaat atacatcaca gtgaaatgtg taatccttgc aaattgcaag 60 ttgaaagaat taaattcaga ggaggggaga gaaagagtac tcagtaggga ctgagcacta 120 aatgcttatt ttaaaagaaa tgtaaagagc agaaagcaat tcaggctacc ctgccttttg 180 tgctggctag tactccggtc ggtgtcagca gcacgtggca ttgaacattg caatgtggag 240 cccaaaccac agaaaatggg gtgaaattgg ccaactttct attaacttgg cttcctgttt 300 tataaaatat tgtgaataat atcacctact tcaaagggca gttatgaggc ttaaatgaac 360 aaaacactta taacgcctac aacatagata acataggtgc aagtactatg tatctggtac 420 atggtaaaca tccttattat taaagtcaac gctaaaatga atgtgtgtgc atatgctaat 480 agtacagaga gagggcactt aaaccaacta agggcctgga gggaaggttt cctggaaaga 540 ngatgcttgt gctgggtcca aatcttggtc tactatgacc ttggccaaat tatttaaact 600 ttgtccctat ctgctaaaca gatc 624
< 210 > 444 < 211 > 425 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (425) < 223 > n = A, T, C or G < 400 > 444 gcacatcatt nntcttgcat tctttgagaa taagaagatc agtaaatagt tcagaagtgg 60 gaagctttgt ccaggcctgt gtgtgaaccc aatgttttgc ttagaaatag aacaagtaag 120 tagcataaca ttcattgcta caaaatttgc ataagtggtg gtcagcaaat ccttgaatgc 180 tgcttaatgt gagaggttgg taaaatcctt tgtgcaacac tctaactccc tgaatgtttt 240 gacctgtgca gctgtgctgg tgccagacaa ggccaagctg gctgaaagag caaccagcca 300 cctctgcaat ctgccacctc ctgctggcag gatttgtttt tgcatcctgt gaagagccaa 360 ggaggcacca gggcataagt gagtagactt atggtcgacg cggccgcgaa tttagtagta 420 gtaga 425
< 210 > 445 < 211 > 414 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (414) < 223 > n = A, T, C or G < 400 > 445 catgtttatg nttttggatt actttgggca cctagtgttt ctaaatcgtc tatcattctt 60 ttctgttttt gatggccaga caaaagcaga gtctcaacaa actgtatctt caagtctttg 120 tgaaattctt tgcatgtggc agattattgg atgtagtttc ctttaactag catataaatc 180 tggtgtgttt cagataaatg aacagcaaaa tgtggtggaa ttaccatttg gaacattgtg 240 tgtgtctcta aatgaaaaat caaataacta gattatgtaa tttcctaacc attgatcttt 300 ggatttttat aatcctactc acaaatgact aggcttctcc tcttgtattt tgaagcagtg 360 tgggtgctgg attgataaaa aaaaaaaaag tcgacgcggc cgcgaattta GTAG_414_< 210 > 446 < 211 > 631 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (631) < 223 > n = A, T, C or G < 400 > 446 acaaattaga anaaagtgcc agagaacacc acataccttg tccggaacat tacaatggct 60 tgggaagtgt tctgcatgca gagcattcta tcaatatgca ggagccatct tgcaggtgtg 120 tactggacaa atgctggtta aaaaggacta cactgtgaaa cagtgttcta tacgttgttc 180 ccggtcctgt acgatttcag tatgtcttaa tcgcagctgt gattggaaca attcagattg 240 ctgtcatctg tgtggtggtc ctctgcatca caagggccaa actttaggta atagcattgg 300 actgagattt gtaaactttc caaccttcca ggaaatgccc cagaagcaac agaattcaca 360 gacagaagca aaatacaggg cactacagtt cagacaatac aacaagagcg tccacgaggt 420 taatctaaag ggagcatgtt tcacagtggc tggactaccg agagcttgga ctacacaata 480 cagtattata gacaaaagaa taagacaaga gatctacaca tgttgccttg catttgtggt 540 aatctacacc aatgaaaaca tgtactacag ctatatttga ttatgtatgg atatatttga 600 aatagtatac attgtcttga tgttttttct g 631
< 210 > 447 < 211 > 585 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (585) < 223 > n = A, T, C or G < 400 > 447 antntcacaa ccttgggaaa tataaagggt cgtagacttt actccaaatt ccaaaaaggt 60 cctggccatg taatcctgaa agttttccca aaaatcctta aggtagctat taagggtgca 120 gcctcttctg gaattcctct gatttcaaag tctcactctc aagttcttga aaacgagggc 180 agttcctgaa aggcaggtat agcaactgat cttcagaaag aggaactgtg tgcaccggga 240 gagtaggata tgggctgcca ggattccaga tgctgacacc ttctggggga aacagggctg 300 ccaggtttgt catagcactc atcaaagtcc ggtcaacgtc tgtgcttcga atataaacct 360 ataggactca gttcatgttt ttcaagaatt ttctatatct tactctccaa ctttcttata 420 gttcataatg ctgctccatg cccagctggg tgagttggcc aaatccttgt ggccatgagg 480 attcctttat ggggtcagtg ggaaaggtgt caatgggact tcggtctcca tgccgaaaca 540 ccaaagtcac aaacttcaac tccttggcta gtacacttcg gtcta 585 < 210 > 448 < 211 > 93 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (93) < 223 > n = A, T, C or G < 400 > 448 tgctcgtggg tcattctgan nnccgaactg accntgccag ccctgccgan gggccnccat 60 ggctccctag tgccctggag agganggggc tag 93 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (706) < 223 > n = A, T, C or G < 400 > 449 ccaagttcat gctntgtgct cagggggcaa ggacgctgga tcgtgggtca aagcnnttgc 6_0_ ttctgancac cgaactgacc atgccagccc tgccgatggt cctccatggc tccctagtgc 120 cctggagagg aggtgtctag tcagagagta gtcctggaag gtggcctctg ngaggagcca 180 cggggacagc atcctgcaga tggtcgggcg cgtcccattc gccattcagg ctgcgcaact 240 gttgggaagg gcgatcggtg cgggcctctt cgctattacg ccagctggcg aaagggggat 300 gtgctgcaag gcgattaagt tgggtaacgc cagggttttc cgttgtaaaa ccagtcncga 360 cgacggccag tgaattgaat ttaggtgacn ctatagaaga gctatgacgt cgcatgcacg 420 cgtacgtaag cttggatcct ctagagcggc cgcctactac tactaaattc gcggccgcgt 480 tccncactga cgacgtggga gagagtggag agtgacatgt gctggacnct gtccatgaag 540 cactgagcag aagctggagg cacaacgcnc cagctactca cagacactca ggaggctgag 600 aacaggttga acctgggagg tggaggttgc aatgagctga ctgcncccca gatcaggccn 660 cagagtgaaa gcatggatga aaaaaaaaaa aaaaaa 706 ctccatctta
< 210 > 450 < 211 > 493 < 212 > DNA < 213 > Homo sapiens < 400 > 450 gagacggagt gtcactctgt tgcccaggct ggagtgcagc aagacactgt czaagaaaaa 60 acagttttaa aaggtaaaac aacataaaaa gaaatatcct atagtggaaa taagagagtc 120 aaatgaggct gagaacttta caaagggatc ttacagacat gtcgccaata tcactqcatg 180 agcctaagta taagaacaac ctttggggag aaaccatcat ttgacagtga ggcacaattc 240 caagtcaggt agtgaaatgg gtggaattaa actcaaatta atcctgccag ctgaaacgca 300 agagacactg tcagagagtt aaaaagtgag ttctatccat gaggtgattc cacaqtcttc 360 tcaagtcaac acatctgtga actcacagac caagttctta aaccactgtt caaactctgc 420 tacacatcag aatcacctgg agagctttac aaactcccat tgccgagggt cgacgcggcc 480 gcgaatttag tag 493
< 210 > 451 < 211 > 501 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (501) < 223 > n = A, T, C or G < 400 > 451 gggcgcgtcc cattcgccat tcaggctgcg caactgttgg gaagggcgat cggtgcgggc 60 ctcttcgcta ttacgccagc tggcgaaagg gggatgtgct gcaaggcgat taagttgggt 120 aacgccaggg ttttcccagt cncgacgttg taaaacgacg gccagtgaat tgaatttagg 180 tgacnctata gaagagctat gacgtcgcat gcacgcgtac gtaagcttgg atcctctaga 240 gcggccgcct actactacta aattcgcggc cgcgtcgacg tgggatccnc actgagagag 300 tggagagtga catgtgctgg acnctgtcca tgaagcactg agcagaagct ggaggcacaa 360 cgcnccagac actcacagct actcaggagg ctgagaacag gttgaacctg ggaggtggag 420 gttgcaatga gctgagatca ggccnctgcn ccccagcatg gatgacagag tgaaactcca 480 tcttaaaaaa aaaaaaaaaa a 501
< 210 > 452 < 211 > 51 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (51) < 223 > n = A, T, C or G < 400 > 452 agacggtttc accnttacaa cnccttttag gatgggnntt ggggagcaag c 51
< 210 > 453 < 211 > 317 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (317) < 223 > n = A, T, C or G < 400 > 453 tacatcttgc tttttcccca ttggaactag tcattaaccc atctctgaac tggtagaaaa 60 acatctgaag agctagtcta tcagcatctg gcaagtgaat tggatggttc tcagaaccat 120 ttcacccana cagcctgttt ctatcctgtt taataaatta gtttgggttc tctacatgca 180 taacaaaccc tgctccaatc tgtcacataa aagtctgtga cttgaagttt antcagcacc 240 cccaccaaac tttatttttc tatgtgtttt ttgcaacata tgagtgtttt gaaaataagg 300 tacccatgtc tttatta 317
< 210 > 454 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 454 ttcgaggtac aatcaactct cagagtgtag tttccttcta tagatgagtc agcattaata 60 taagccacgc cacgctcttg aaggagtctt gaattctcct ctgctcactc agtagaacca 120 agaagaccaa attcttctgc atcccagctt gcaaacaaaa ttgttcttct aggtctccac 180 ccttcctttt tcagtgttcc aaagctcctc acaatttcat gaacaacagc t 231
< 210 > 455 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 455 taccaaagag ggcataataa tcagtctcac agtagggttc accatcctcc aagtgaaaaa 60 cattgttccg aatgggcttt ccacaggcta cacacacaaa acaggaaaca tgccaagttt 120 gtttcaacgc attgatgact tctccaagga tcttcctttg gcatcgacca cattcagggg 180 caaagaattt ctcatagcac agctcacaat acagggctcc tttctcctct a 231
< 210 > 456 < 211 > 231 < 2I2 > DNA < 213 > Homo sapiens < 400 > 456 cccttacaaa ttggcaggta gaagacacca taccttatgc gttattaggt ggaataatca 60 ttccattcag tattatcgtt attattcttg gagaaaccct gtctgtttac tgtaaccttt 120 tgcactcaaa ttcctttatc aggaataact acatagccac tatttacaaa gccattggaa 180 cctttttatt tggtgcagct gctagtcagt ccctgactga cattgccaag t 231 < 210 > 457 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (231) < 223 > n = A, T, C or G < 400 > 457 cgaggtaccc aggggtctga aaatctctnn tttantagtc gatagcaaaa ttgttcatca 60 gcattcctta atatgatctt gctataatta gatttttctc cattagagtt catacagttt 120 tatttgattt tattagcaat ctctttcaga agacccttga gatcattaag ctttgtatcc 180 agttgtctaa atcgatgcct catttcctct gaggtgtcgc tggcttttgu g 231
< 210 > 458 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 458 aggtctggtt ccccccactt ccactcccct ctactctctc taggactggg ctgggccaag 60 agaagagggg tggttaggga agccgttgag acctgaagcc ccaccctcta ccttccttca 120 acaccctaac cttgggtaac agcatttgga attatcattt gggatgagta gaatttccaa 180 ggtcctgggt taggcatttt ggggggccag accccaggag aagaagattc t 231
< 210 > 459 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 459 ggtaccgagg ctcgctgaca cagagaaacc ccaacgcgag gaaaggaatg gccagccaca 60 ccttcgcgaa acctgtggtg gcccaccagt cctaacggga caggacagag agacagagca 120 gccctgcact gttttccctc caccacagcc atcctgtccc tcattggctc tgtgctttcc 180 actatacaca gtcaccgtcc caatgagaaa caagaaggag caccctccac a 231
< 210 > 460 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 460 gcaggtataa catgctgcaa caacagatgt gactaggaac ggccggtgac atggggaggg 60 cctatcaccc tattcttggg ggctgcttct tcacagtgat catgaagcct agcagcaaat 120 cacacgcaca cccacctccc cggccagcct ggagcccaca cctgcagcca gaagggtcct 180 gtggagcttg gtccagcctc cagtccaccc ctaccaggct taaggataga 231
< 210 > 461 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 461 gaagctctaa cgaggtttga tgtgcagggg agccgagaag caggcggcct agggagggtc 60 gcgtgtgctc cagaagagtg tgtgcatgcc agaggggaaa caggcgcctg tgtgtcctgg 120 gtggggttca gtgaggagtg ggaaattggt tcagcagaac caagccgttg ggtgaataag 180 agggggattc catggcactg atagagccct atagtttcag agctgggaat t 231
< 210 > 462 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 462 aggtaccctc attgtagcca tgggaaaatt gatgttcagt ggggatcagt gaattaaatg 60 gggtcatgca agtataaaaa ttaaaaaaaa aagacttcat gcccaatctc atatgatgtg 120 gaagaactgt tagagagacc aacagggtag tgggttagag atttccagag tcttacattt 180 tctagaggag gtatttaatt tcttctcact catccagtgt tgtatttagg a 231 < 210 > 463 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 463 tactccagcc tggtgacaga gcgagaccct atcaccgccc cccaccccac caaaaaaaaa 60 actgagtaga caggtgtcct cttggcatgg taagtcttaa gtcccctccc agatctgtga 120 catttgacag gtgtcttttc ctctggacct cggtgtcccc atctgagtga gaaaaggcag 180 tggggaggtg gatcttccag tcgaagcggt atagaagccc gtgtgaaaag c 231
< 210 > 464 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 464 gtactctaag attttatcta agttgccttt tctgggtggg aaagtttaac cttagtgact 60 aaggacatca catatgaaga atgtttaagt tggaggtggc aacgtgaatt gcaaacaggg 120 cctgcttcag tgactgtgtg cctgtagtcc cagctactcg ggagtctgtg tgaggccagg 180 ggtgccagcg caccagctag atgctctgta acttctaggc cccattttcc c 231
< 210 > 465 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 465 catgttgttg tagctgtggt aatgctggct gcatctcaga cagggttaac ttcagctcct 60 gtggcaaatt agcaacaaat tctgacatca tatttatggt ttctgtatct ttgttgatga 120 aggatggcac aatttttgct tgtgttcata atatactcag attagttcag ctccatcaga 180 taaactggag acatgcagga cattagggta gtgttgtagc tctggtaatg a 231
< 210 > 466 < 211 > 231 < 212 > DNA < 213 > Homo sapiens < 400 > 466 caggtacctc tttccattgg atactgtgct agcaagcatg ctctccgggg tttttttaat 60 ggccttcgaa cagaacttgc cacataccca ggtataatag tttctaacat ttgcccagga 120 cctgtgcaat caaatattgt ggagaattcc ctagctggag aagtcacaaa gactataggc 180 aataatggag accagtccca caagatgaca accagtcgtt gtgtgcggct g 231
< 210 > 467 < 211 > 311 < 212 > DNA < 213 > Homo sapiens < 400 > 467 gtacaccctg gcacagtcca atctgaactg gttcagcact catctttcat gagatggatg 60 tggtggcttt tctccttttt catcaagact cctcagcagg gagcccagac cagcctgcac 120 tgtgccttaa caaaaggtct tgagattcta agtgggaatc atttcagtga ctgtcatgtg 180 gcatgggtct ctgcccaagc tcgtaatgag actatagcaa ggcggctgtg ggacgtcagt 240 tgtgacctgc tgggcctccc aatagactaa caggcagtgc cagttggacc caaaagaaga ctgcagcaga c 300 311 < 210 > 468 < 211 > 3112 < 212 > DNA < 213 > Homo sapiens < 400 > 468 cattgtgttg ggagaaaaac agaggggaga tttgtgtggc tgcagccgag ggagaccagg 60 aagatctgca tggtgggaag gacctgatga tacagagttt gataggagac aattaaaggc 120 tggaaggcac tggatgcctg atgatgaagt ggactttcaa actggggcac tactgaaacg 180 atgggatggc cagagacaca ggagatgagt tggagcaagc tcaataacaa agtggttcaa 240 cgaggacttg gaattgcatg gagctggagc tgaagtttag cccaattgtt tactagttga 300 gtgaatgtgg atgattggat gatcatttct catctctgag cctcaggttc cccatccata 360 cacagtatga aaatgggata tctataaagt gggatatagt atgatctact tcactgggtt 420 atttgaagga tgaattgaga taatttattt gaacaatgcc caggtgccta cagattagta -480 aactgagaaa catttggtgg ccaaatttaa tggcataaca tatatgtcag atgttactat 540 caatctcata gattatcatt gttttgtcat ggcccaattt atcctcactt gtgcctcaac 600 aaattgaact gttaacaaag gaatctctgg tcctgggtaa tggctgagca ccactgagca 660 tttccattcc agttggcttc ttgggtttgc tagctgcatc actagtcatc ttaaataaat 720 catttctcca gaagttttaa gtgatttttt tatctcacct ttgaagatac tatgttatgt 780 gattaaataa agaacttgag aagaacaggt ttcattaaac tgtagacgca ataaaatcaa 840 aattttctgg atggg cttatgttca CAATA caggaaatgc tttaaaatat gcagaagata 900 attaaatggc aatggacaaa gtgaaaaact tagacttttt tttttttttt ggaagtatct 960 ggatgttcct tagtcactta aaggagaact gaaaaatagc agtgagttcc acataatcca 1020 acctgtgaga ttaaggctct ttgtggggaa ggacaaagat ctgtaaattt acagtttcct 1080 tccaaagcca acgtcgaatt ttgaaacata tcaaagctct tcttcaagac aaataatcta 1140 tagtacatct ttcttatggg atgcacttat gaaaaatggt ggctgtcaac atctagtcac 1200 tttagctctc aaaatggttc attttaagag aaagttttag aatctcatat ttattcctgt 1260 ggaaggacag cattgtggct tggactttat aaggtcttta ttcaactaaa taggtgagaa 1320 ataagaaagg ctgctgactt taccatctga ggccacacat ctgctgaaat ggagataatt 1380 gaaacagcaa aacatcacta gatgacaata taatgtctaa gtagtgacat gtttttgcac 1440 cctttaaata atttccagcc tccacacaca caggaagcac aaaaggaagc acagagatcc 1500 ctgggagaaa tgcccggccg ccatcttggg tcatcgatga gcctcgccct gtgcctggtc 1560 gggaaggaca ccgcttgtga ttagaaaatg aattgatgtg ttccttaaag gatgggcagg 1620 aaaacagatc ctgttgtgga tatttatttg aacgggatta cagatttgaa atgaagtcac 1680 ttaccaatga aaagtgagca ga ggaaaaca gacgagaaaa tcttgatggc ttcacaagac 1740 caaaatggaa atgcaacaaa tactgtgatg acatgaggca gccaagctgg ggaggagata 1800 accacggggc agagggtcag gattctggcc ctgctgccta aactgtgcgt tcataaccaa 1860 atcatttcat atttctaacc ctcaaaacaa agctgttgta atatctgatc tctacggttc 1920 cttctgggcc caacattctc gccacactca catatatcca tttttaatat ttagttccca 1980 gatctgtact gtgacctttc tacactgtag aataacatta ctcattttgt tcaaagaccc 2040 ttcgtgttgc tgcctaatat gtagctgact gtttttccta aggagtgttc tggcccaggg 2100 caggctggga gatctgtgaa agcatctcaa gatctttcca gggttatact tactagcaca 2160 cagcatgatc attacggagt gaattatcta atcaacatca tcctcagtgt ctttgcccat 2220 actgaaattc atttcccact tttgtgccca ttctcaagac ctcaaaatgt cattccatta 2280 atatcacagg attaactttt ttttttaacc tggaagaatt caatgttaca tgcagctatg 2340 ggaatttaat tacatatttt gttttccagt gcaaagatga ctaagtcctt tatccctccc 2400 ctttgtttga ttttttttcc agtataaagt taaaatgctt agccttgtac tgaggctgta 2460 tacagccaca gcctctcccc atccctccag ccttatctgt catcaccatc aacccctccc 2520 acaaaatcta atgcacctaa acttgtaatt ccttgaacat gtcaggcata cattattcct 2580 tctgcctgag aagctcttcc ttgtctctta aatctagaat gatgtaaagt tttgaataag 2640 ttgactatct tacttcatgc aaagaaggga cacatatgag attcatcatc acatgagaca 2700 gcaaatacta aaagtgtaat ttgattataa gagtttagat aaatatatga aatgcaagag 2760 ccacagaggg aatgtttatg gggcacgttt gtaagcctgg gatgtgaagc aaaggcaggg 2820 aacctcatag tatcttatat aatatacttc atttctctat ctctatcaca atatccaaca 2880 agcttttcac agaattcatg cagtgcaaat ccccaaaggt aacctttatc catttcatgg 2940 tgagtgcgct ttagaatttt ggcaaatcat actggtcact tatctcaact ttgagatgtg 3000 tttgtccttg tagttaattg aaagaaatag ggcactcttg tgagccactt tagggttcac caaagagcaa 3060 aaaaaaaaaa aaaaaaaaaa tcctggcaat aaagaattta aa 3112
< 210 > 469 < 211 > 2229 < 212 > DNA < 213 > Homo sapiens < 400 > 469 agctctttgt aaattcttta ttgccaggag tgaaccctaa agtggctcac aagagtgccc 60 tatttctttc aattaactac aaggacaaac gttgagataa acatctcaaa gtgaccagta 120 aaattctaaa tgatttgcca gcgcactcac catgaaatgg ataaaggtta cctttgggga 180 tttgcactgc atgaattctg tgaaaagctt gttggatatt gtgatagaga tagagaaatg 240 aagtatatta tataagatac tatgaggttc cctgcctttg cttcacatcc caggcttaca 300 aacgtgcccc ataaacattc cctctgtggc tcttgcattt catatattta tctaaactct 360 tacactttta tataatcaaa gtatttgctg tctcatgtga tgatgaatct catatgtgtc 420 ccttctttgc atgaagtaag atagtcaact tattcaaaac tttacatcat tctagattta 480 agagacaagg aagagcttct caggcagaag gaataatgta tgcctgacat gttcaaggaa 540 ttacaagtta gattttgttt aggtgcatgg gaggggttga tggtgatgac agataaggct 600 ggagggatgg ggagaggctg tggctgtata cagcctcagt acaaggctaa gcattttaac 660 tttatactgg aaaaaaaatc aaacaaaggg gagggataaa ggacttagtc atctttgcac 720 tggaaaacaa aatatgtaat taaattccca tagctgcatg taacattgaa ttcttccagg 780 agttaatcct ttaaaaaaaa gtgatattaa tggaatgaca ttttgaggtc ttgagaatgg 840 gcacaaaagt gggaaa tgaa ggcaaagaca tttcagtatg ctgaggatga tgttgattag 900 ataattcact ccgtaatgat catgctgtgt gctagtaagt ataaccctgg aaagatcttg 960 agatgcttcc cagcctgttc acagatcccc tgggccagaa cactccttag gaaaaacagt 1020 cagctacata ttaggcagca tctttgaaca acacgaaggg aaatgagtaa tgttattcta 1080 cagtgtagaa aggtcacagt acagatctgg gaactaaata ttaaaaatga gtgtggctgg 1140 atatatggag aatgttgggc ccagaaggaa ccgtagagat cagatattac aacagctttg 1200 ttttgagggt tagaaatatg aaatgatttg gttatgaacg cacagtttag gcagcagggc 1260 cagaatcctg accctctgcc ccgtggttat ctcctcccca gcttggctgc ctcatgtcat 1320 cacagtattc cattttgttt gttgcatgtc ttgtgaagcc atcaagattt tctcgtctgt 1380 tttcctctca ttggtaatgc tcactttgtg acttcatttc aaatctgtaa tcccgttcaa 1440 ataaatatcc acaacaggat ctgttttcct gcccatcctt taaggaacac atcaattcat 1500 tttctaatgt ccttccctca caagcgggac caggcacagg gcgaggctca tcgatgaccc 1560 aagatggcgg ccgggcattt ctcccaggga tctctgtgct tccttttgtg cttcctgtgt 1620 gtgtggatat ttaaaggggc tggaaatgtg caaaaacatg cactactta gacattatat 1680 tgtcatcttg ctgtttctag tgat gttaat tatctccatt tcagcagatg tgtggcctca 1740 gatggtaaag tcagcagcct ttcttatttc tcacctggaa atacatacga ccatttgagg 1800 agacaaatgg caaggtgtca gcataccctg aacttgagtt gagagctaca cacaatatta 1860 agcatcacaa ttggtttccg acaccctctc tgtttcttca ctgggcacag aattttaata 1920 cttatttcag tgggctgttg gcaggaacaa atgaagcaat ctacataaag tcactagtgc 1980 agtgcctgac acacaccatt ctcttgaggt cccctctaga gatcccacag gtcatatgac 2040 ttcttgggga gcagtggctc acacctgtaa tcccagcact ttgggaggct gaggcaggtg 2100 ggtcacctga ggtcaggagt tcaagaccag cctggccaat atggtgaaac cccatctcta 2160 ctaaaaatac aaaaattagc tgggcgtgct ggtgcatgcc tgtaatccca gccccaacac 2220 aatggaa ctt 2229
< 210 > 470 < 211 > 2426 < 212 > DNA < 213 > Homo sap iens < 400 > 470 gtaaattctt tattgccagg agtgaaccct aaagtggctc acaagagtgc cctatttctt 60 tcaattaact acaaggacaa acacatctca aagttgagat aagtgaccag tatgatttgc 120 caaaattcta aagcgcactc accatgaaat ggataaaggt tacctttggg gatttgcact 180 tgtgaaaagc gcatgaattc ttgttggata ttgtgataga gatagagaaa tgaagtatat 240 tatataagat actatgaggt tccctgcctt tgcttcacat cccaggctta caaacgtgcc 300 ccataaacat tccctctgtg gctcttgcat ttcatatatt tatctaaact cttataatca 360 aattacactt ttagtatttg ctgtctcatg tgatgatgaa tctcatatgt gtcccttctt 420 tgcatgaagt acttattcaa aagatagtca aactttacat cattctagat ttaagagaca 480 aggaagagct tctcaggcag aaggaataat gtatgcctga catgttcaag gaattacaag 540 ttagattttg tttaggtgca tgggaggggt tgatggtgat gacagataag gctggaggga 600 tggggagagg ctgtggctgt atacagcctc agtacaaggc taagcatttt aactttatac 660 atcaaacaaa tggaaaaaaa ggggagggat aaaggactta gtcatctttg cactggaaaa 720 caaaatatgt aattaaattc ccatagctgc atgtaacatt gaattcttcc aggttaaaaa 780 tcctgtgata aaaaagttaa ttaatggaat gacattttga ggtcttgaga atgggcacaa 840 aagtgggaaa tgaatt tcag tatgggcaaa gacactgagg atgatgttga ttagataatt 900 cactccgtaa tgatcatgct gtgtgctagt aagtataacc ctggaaagat cttgagatgc 960 ttcccagcct gttcacagat cccctgggcc agaacactcc ttaggaaaaa cagtcagcta 1020 catattaggc agcaacacga agggtctttg aacaaaatga gtaatgttat tctacagtgt 1080 cagtacagat agaaaggtca ctgggaacta aatattaaaa atgagtgtgg ctggatatat 1140 ggagaatgtt gggcccagaa ggaaccgtag agatcagata ttacaacagc tttgttttga 1200 tatgaaatga gggttagaaa tttggttatg aacgcacagt ttaggcagca gggccagaat 1260 cctgaccctc tgccccgtgg ttatctcctc cccagcttgg ctgcctcatg tcatcacagt 1320 gtttgttgca attccatttt tgtcttgtga agccatcaag attttctcgt ctgttttcct 1380 ctcattggta atgctcactt tgtgacttca tttcaaatct gtaatcccgt tcaaataaat 1440 atccacaaca ggatctgttt tcctgcccat cctttaagga acacatcaat tcattttcta 1500 atgtccttcc ctcacaagcg ggaccaggca cagggcgagg ctcatcgatg acccaagatg 1560 gcggccgggc atttctccca gggatctctg tgcttccttt tgtgcttcct gtgtgtgtgg 1620 atatttaaag gggctggaaa tgtgcaaaaa catgtcacta cttagacatt atattgtcat 1680 cttgctgttt ctagtgatgt taattatctc catttcagca gatgtgtggc ctcagatggt 1740 gcctttctta aaagtcagca tttctcacct ggaaatacat acgaccattt gaggagacaa 1800 atggcaaggt gtcagcatac cctgaacttg agttgagagc tacacacaat attattggtt 1860 tccgag CATC acaaacaccc tctctgtttc ttcactgggc acagaatttt aatacttatt 1920 tcagtgggct gttggcagga acaaatgaag caatctacat aaagtcacta gtgcagtgcc 1980 tgacacacdc cattctcttg aggtcccctc tagagatccc acaggtcata tgacttcttg 2040 gggagcagtg gctcacacct gtaatcccag ggctgaggca cactttggga ggtgggtcac 2100 ctgaggtcag gagttcaaga ccagcctggc caatatggtg aaaccccatc tctactaaaa 2160 atacaaaaat tagctgggcg tgctggtgca tgcctgtaat cccagctact tgggaggctg 2220 attgctggaa aggcaggaga catgggaggc ggaggttgca gtgagctgta attgtgccat 2280 tgcactcgaa cctgggcgac agagtggaac tctgtttcca aaaaacaaac aaacaaaaaa 2340 ggcatagtca gatacaacgt gggtgggatg tgtaaataga agcaggatat aaagggcatg 2400 gggtgacggt tttgcccaac acaatg 2426
< 210 > 471 < 211 > 812 < 212 > DNA < 213 > Homo sapiens < 400 > 471 gaacaaaatg agtaatgtta ttctacagtg tagaaaggtc acagtacaga tctgggaact 60 aaatattaaa aatgagtgtg gctggatata tggagaatgt tgggcccaga aggaaccgta 120 gagatcagat attacaacag ctttgttttg agggttagaa atatgaaatg atttggttat 180 gaacgcacag tttaggcagc agggccagaa tcctgaccct ctgccccgtg gttatctcct 240 ccccagcttg gctgcctcat gtcatcacag tattccattt tgtttgttgc atgtcttgtg 300 aagccatcaa gattttctcg tctgttttcc tctcattggt aatgctcact ttgtgacttc 360 atttcaaatc tgtaatcccg ttcaaataaa tatccacaac aggatctgtt ttcctgccca 420 tcctttaagg aacacatcaa ttcattttct aatgtccttc cctcacaagc gggaccaggc 480 acagggcgag gctcatcgat gacccaagat ggcggccggg catttctccc agggatctct 540 gtgcttcctt ttgtgcttcc tgtgtgtgtg gatatttaaa ggggctggaa atgtgcaaaa 600 acatgtcact acttagacat tatattgtca tcttgctgtt tctagtgatg ttaattatct 660 ccatttcagc agatgtgtgg cctcagatgg taaagtcagc agcctttctt atttctcacc 720 tctgtatcat caggtccttc ccaccatgca gatcttcctg gtctccctcg gctgcagcca 780 812 ag cacaaatctc ccctctgttt ttctgatgcc
< 210 > 472 < 211 > 515 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > diverse feature < 222 > (1) ... (515) < 223 > n = A, T, C or G < 400 > 472 acggagactt attttctgat attgtctgca tatgtatgtt tttaagagtc tggaaatagt 60 cttatgactt tcctatcatg cttattaata aataatacag cccagagaag atgaaaatgg 120 gttccagaat tattggtcct tgcagcccgg tgaatctcag caagaggaac caccaactga 180 caatcaggat attgaacctg gacaagagag agaaggaaca cctccgatcg aagaacgtaa 240 agtagaaggt gattgccagg aaatggatct ggaaaagact cggagtgagc gtggagatgg 300 ctctgatgta aaagagaaga ctccacctaa tcctaagcat gctaagacta aagaagcagg 360 agatgggcag ccataagtta aaaagaagac aagctgaagc tacacacatg gctgatgtca 420 cattgaaaat gtgactgaaa atttgaaaat tctctcaata aagtttgagt tttctctgaa 480 gaaaaaaaaa naaaaaaaaa aaanaaaaan aaaaa 515
Claims (79)
1. An isolated polypeptide comprising at least an immunogenic portion of a prostate tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (a) sequences declared in any of SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93 , 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225 , 227-305, 307-315, 326, 328, 330, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410 , 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 465-471 or 472; (b) sequences that hybridize to any of the above sequences under moderately severe conditions; and (c) complements of any of the sequences of (a) or (b).
2. An isolated polypeptide according to claim 1, wherein the polypeptide comprises an amino acid sequence that is encoded by a polynucleotide sequence declared in any of SEQ ID NOS: 2, 3, 8-29, 41-45, 47 -52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181 , 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 332, 334, 350- 365, 381, 382 , 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 465-471 or 472, or a complement of any of the above polynucleotide sequences.
3. An isolated polypeptide comprising a sequence declared in any of SEQ ID NO: 108, 112, 113, 114, 172, 176, 178, 327, 329, 331, 339 and 383.
4. An isolated polypeptide that encodes at least 15 amino acid residues of a prostate tumor protein, or a variant thereof that differs in one or more substitutions, deletions, additions and / or insertions, so that the ability of the variant to react with antigen-antigen specific is not substantially diminished, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide comprising a sequence declared in any of SEQ ID NOS: 2, 3, 8-29, 41-45, 47 -52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181 , 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 332, 334, 350-365, 381, 382 , 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408 , 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 465-471 or 472, or a complement of any of the previous sequences.
5. An isolated polynucleotide encoding a prostate tumor protein, or a vairant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide comprising a sequence delcarada in any of SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115- 160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 465-471 or 472, or a complement of any of the above sequences.
6. A polynucleotide comprising a sequence declared in any of SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 465-471 or 472.
7. An isolated polynucleotide comprising a hybridizing sequence, under moderately severe, to a sequence declared in any of SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93 , 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225 , 227-305, 307-315, 326, 328, 330, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410 , 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 465-471 or 472.
8. An isolated polynucleotide complementary to a polynucleotide according to any of the claims 4-7.
9. An expression vector comprising a polynucleotide according to any of claims 4-7.
10. A host cell transformed or transfected with an expression vector according to claim 9.
11. An expression vector comprising a polynucleotide according to claim 8.
12. A host cell transformed or transfected with an expression vector. according to claim 11.
13. A pharmaceutical composition comprising a polypeptide according to claim 1, in combination with a physiologically acceptable carrier.
A vaccine comprising a polypeptide according to claim 1, in combination with a non-specific immune response enhancer.
15. A vaccine according to claim 14, wherein the immune response enhancer does not specify is an auxiliary.
16. A vaccine according to claim 14, wherein the immune response enhancer does not specify induces a predominantly Type I response.
17. A pharmaceutical composition comprising a polynucleotide according to claim 4, in combination with a physiologically acceptable carrier.
18. A vaccine comprising a polynucleotide according to claim 4, in combination with a non-specific immune response enhancer.
19. A vaccine according to claim 18, wherein the immune response enhancer does not specify is an auxiliary.
20. A vaccine according to claim 18, wherein the immune response enhancer does not specify induces a predominantly Type I response.
21. An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a tumor prostate comprising an amino acid sequence that is encoded by a polynucleotide sequence declared in any of SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79 , 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204 , 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396 , 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 465-471 or 472 or a complement of any of the above polynucleotide sequences.
22. A pharmaceutical composition comprising an antibody or fragment thereof according to claim 18, in combination with a physiologically acceptable carrier.
23. A pharmaceutical composition comprising a cell that 5 presents an antigen, which expresses a polypeptide according to claim 1, in combination with a pharmaceutically acceptable carrier or excipient.
24. A pharmaceutical composition according to the claim 23, wherein the antigen presenting cell is a dendritic cell or a macrophage.
25. A vaccine comprising an antigen-presenting cell, which expresses a polypeptide according to claim 1, in combination with a non-specific immune response enhancer.
26. A vaccine according to claim 25, wherein the immune response enhancer does not specify is an auxiliary.
27. A vaccine according to claim 25, wherein the immune response enhancer does not specify induces a predominantly Type I response.
28. A vaccine according to claim 25, wherein the antigen presenting cell is a dendritic cell. .
29. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a polypeptide according to claim 1, and 25 thereby inhibiting the development of a cancer in the patient.
30. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a polynucleotide according to claim 4, and thereby inhibiting the development of a cancer in the patient.
31. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of an antibody or antigen-binding fragment thereof according to claim 21, and thereby inhibiting the development of a cancer. in the patient.
32. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of an antigen presenting cell expressing a polypeptide according to claim 1, and thereby inhibiting the development of a cancer in a patient. the patient.
33. A method according to claim 32, wherein the antigen-presenting cell is a dendritic cell.
34. A method according to any of claims 29-32, wherein the cancer is prostate cancer.
35. A fusion protein comprising at least one polypeptide according to claim 1.
36. A fusion protein according to claim 35, wherein the fusion protein comprises an expression enhancer that increases the expression of the protein of fusion in a host cell transfected with a polynucleotide encoding the fusion protein.
37. A fusion protein accng to claim 35, wherein the fusion protein comprises an auxiliary epitope T which is not present within the polypeptide of claim 1.
38. A fusion protein accng to claim 35, wherein the fusion protein comprises an affinity tag.
39. An isolated polypeptide encoding a fusion protein accng to claim 35.
40. A pharmaceutic composition comprising a fusion protein accng to claim 32, in combination with a physiologically acceptable carrier.
41. A vaccine comprising a fusion protein accng to claim 35, in combination with a non-specific immune response enhancer.
42. A vaccine accng to claim 41, wherein the immune response enhancer does not specify is an auxiliary.
43. A vaccine accng to claim 41, wherein the immune response enhancer does not specify induces a predominantly Type I response.
44. A pharmaceutical composition comprising a polynucleotide accng to claim 40, in combination with a physiologically acceptable carrier.
45. A vaccine comprising a polynucleotide accng to the re-excitation 40, in combination with a non-specific immune response enhancer.
46. A vaccine accng to claim 45, wherein the immune response enhancer does not specify is an adjuvant.
47. A vaccine accng to claim 45, wherein the immune response enhancer does not specify induces a predominantly Type I response.
48. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a pharmaceutical composition accng to claim 40 or claim 44.
49. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a vaccine accng to claim 41 or claim 45.
50. A method for removing tumor cells from a biological sample, which comprises contacting a biological sample with reacting T cells. specifically with a prostate tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of f (i) polynucleotides declared in any of SEQ ID NOS: 1 -111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340, -375, 381, 382 or 384-472; and (ii) complements of the above polynucleotides; wherein the contact step is carried out under conditions and for a sufficient time to allow the removal of cells expressing the prostate tumor protein from the sample.
51. A method accng to claim 50, wherein the biological sample is blood or a fraction thereof.
52. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient a biological sample treated accng to the method of claim 50.
53. A method for stimulating and / or expanding specific T cells for a prostate tumor protein, which comprises contacting T cells with one or more of: (i) a polypeptide accng to claim 1; (ii) a polypeptide encoded by a polynucleotide comprising a sequence provided in any of SEQ ID NOS: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332 -335, 340-375, 381, 382 or 384-472; (iii) a polynucleotide that encodes a polypeptide of (i) or (ii); and / or (iv) an antigen presenting cell expressing a polypeptide of (i) or (ii); under conditions and for a time sufficient to allow the stimulation and / or expansion of T cells.
54. A population of isolated T cells, comprising T cells prepared accng to the method of claim 53.
55. A method for inhibiting the development of a cancer in a patient, comprising administering an effective amount of a population of T cells according to claim 54.
56. A method for inhibiting the development of a cancer in a patient, comprising steps of: (a) incubating CD4 + and / or CD8 + T cells isolated from a patient with at least one component selected from the group consisting of: (i) a polypeptide according to claim 1; (ii) a polypeptide encoded by a polypeptide comprising a sequence of any of SEQ ID NOS: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332- 335, 340-375, 381, 382 or 384-472; (iii) a polynucleotide encoding a polypeptide of (i) or (ii); or (iv) an antigen presenting cell expressing a polypeptide of (i) or (ii); so that T cells proliferate; and (b) administering to the patient an effective amount of the proliferated T cells, and thereby inhibiting the development of a cancer in the patient.
57. A method for inhibiting the development of a cancer in a patient, comprising the steps of: (a) incubating CD4 + and / or CD8 + T cells isolated from a patient with at least one component selected from the group consisting of: (i) ) a polypeptide according to claim 1; (ii) a polypeptide encoded by a polypeptide comprising a sequence of any of SEQ ID NOS: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332- 335, 340-375, 381, 382 or 384-472; (iii) a polynucleotide that encodes a polypeptide of (i) or (ii); or (iv) a cell having antigen expressing a polypeptide of (i) or (ii); so that T cells proliferate; and (b) cloning at least one proliferated cell; and (c) administering to the patient an effective amount of the cloned T cells, and thereby inhibiting the development of a cancer in the patient.
58. A method for determining the presence or absence of a cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient with a binding agent that binds to a prostate tumor protein, in wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of: (i) polynucleotides declared in any of SEQ ID NOS: 1-111, 115-171, 173-175, 177 , 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472; and (ii) complements of the above polynucleotides; (b) detecting in the sample an amount of polypeptide that binds to the binding agent; and (c) comparing the amount of polypeptide to a predetermined cut-off value, and hence determining the presence or absence of a cancer in the patient.
59. A method according to claim 58, wherein the binding agent is an antibody.
60. A method according to claim 59, wherein the antibody is a monoclonal antibody.
61. A method according to claim 58, wherein the cancer is prostate cancer.
62. A method for monitoring the progression of a cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient at a first point in time with a binding agent that binds to a protein of prostate tumor, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence declared in any of SEQ ID NOS: 1-111, 115-171, 173-175, 177, 179-305, 307 -315, 326", 328, 330, 332-335, 340-375, 381, 382 or 384-472, or a complement of any of the above polynucleotides; (b) detect in the sample an amount of polypeptide that binds to the binding agent, (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time, and (d) comparing the amount of polypeptide detected in step (c) with the amount detected in step (b), and then monitor the progression of cancer in the patient. 3.
A method according to claim 62, wherein the binding agent is an antibody.
64. A method according to claim 63, wherein the antibody is a monoclonal antibody.
65. A method according to claim 62, wherein the cancer is a prostate cancer.
66. A method for determining the presence or absence of a cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes a prostate tumor protein , wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence declared in any of SEQ ID NOS: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472, or a complement of any of the above polynucleotides; (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; and (c) comparing the amount of polynucleotide that hybridizes to the oligonucleotide at a predetermined cut-off value, and determining from there the presence or absence of a cancer in the patient.
67. A method according to claim 66, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a polymerase chain reaction.
68. A method according to claim 66, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a hybridization assay.
69. A method for monitoring the progression of a cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide encoding a prostate tumor protein, in wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence declared in any of SEQ ID NOS: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472, or a complement of any of the above polynucleotides; (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and (d) comparing the amount of polynucleotide detected in step (c) with the amount detected in step (b), and monitoring from there the progression of the cancer in the patient.
70. A method according to claim 69, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a polymerase chain reaction.
71. A method according to claim 69, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a hybridization assay.
72. A diagnostic assembly, comprising: (a) one or more antibodies according to claim 21; and (b) a detection reagent comprising a reporter group.
73. An assembly according to claim 72, wherein the antibodies are immobilized on a solid support.
74. An assembly according to claim 73, wherein the solid support comprises nitrocellulose, latex or a plastic material.
75. A kit according to claim 72, wherein the detection reagent comprises an anti-immunoglobulin, protein G, protein A or lectin.
76. A set according to claim 72, wherein the reporter group is selected from the group consisting of radioisotopes, fluorescent groups, luminescent groups, enzymes, biotin and coloring particles.
77. An oligonucleotide comprising 10 to 40 nucleotides that hybridize under moderately severe conditions to a polynucleotide encoding a prostate tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence declared in either of SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107 , 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315 , 326, 328, 330, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 465-471 or 472 or a complement of either of the above polynucleotides.
78. An oligonucleotide according to claim 77, wherein the oligonucleotide comprises 10-40 nucleotides declared in any of SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 465-471 or 472.
79. A diagnostic set, comprising: (a) an oligonucleotide according to claim 77; and (b) a diagnostic reagent for use in a hybridization or polymerase chain reaction assay.
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
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US09116134 | 1998-07-14 | ||
US09115453 | 1998-07-14 | ||
US09/159,822 | 1998-09-23 | ||
US09159812 | 1998-09-23 | ||
US09232880 | 1999-01-15 | ||
US09232149 | 1999-01-15 | ||
US09/288,946 | 1999-04-09 |
Publications (1)
Publication Number | Publication Date |
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MXPA01000432A true MXPA01000432A (en) | 2002-05-09 |
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ID=
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