[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

KR101974169B1 - 재조합 단순 헤르페스 바이러스 및 이의 제조방법 - Google Patents

재조합 단순 헤르페스 바이러스 및 이의 제조방법 Download PDF

Info

Publication number
KR101974169B1
KR101974169B1 KR1020180094006A KR20180094006A KR101974169B1 KR 101974169 B1 KR101974169 B1 KR 101974169B1 KR 1020180094006 A KR1020180094006 A KR 1020180094006A KR 20180094006 A KR20180094006 A KR 20180094006A KR 101974169 B1 KR101974169 B1 KR 101974169B1
Authority
KR
South Korea
Prior art keywords
hsv
region
nucleotide sequence
rpsl
neo
Prior art date
Application number
KR1020180094006A
Other languages
English (en)
Inventor
최경주
김주항
Original Assignee
의료법인 성광의료재단
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 의료법인 성광의료재단 filed Critical 의료법인 성광의료재단
Priority to KR1020180094006A priority Critical patent/KR101974169B1/ko
Application granted granted Critical
Publication of KR101974169B1 publication Critical patent/KR101974169B1/ko
Priority to PCT/KR2019/010068 priority patent/WO2020032680A1/ko
Priority to CN201980051993.6A priority patent/CN112534048A/zh
Priority to JP2021506935A priority patent/JP7138234B2/ja

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011Details
    • C12N2710/16011Herpesviridae
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011Details
    • C12N2710/16011Herpesviridae
    • C12N2710/16032Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011Details
    • C12N2710/16011Herpesviridae
    • C12N2710/16051Methods of production or purification of viral material

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Virology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

재조합 단순 헤르페스 바이러스 1형(HSV-1), 재조합 HSV-1 벡터, 및 이의 제조방법에 관한 것이다. 일 양상에 따른 재조합 HSV-1은 ICP6 및 IR 영역이 동시에 결실됨으로써 비교적 큰 크기의 외래 유전자를 삽입하거나 다양한 외래 유전자를 동시에 삽입할 수 있어 유전자 조작이 용이하다. 또한, 안전하면서도 암세포 살상 효과가 우수한 항암 바이러스로서 암 치료 분야에 다양하게 활용될 수 있다.

Description

재조합 단순 헤르페스 바이러스 및 이의 제조방법 {Recombinant herpes simplex virus and method for manufacturing the same}
재조합 단순 헤르페스 바이러스 1형(HSV-1), 재조합 HSV-1 벡터, 및 이의 제조방법에 관한 것이다.
단순 헤르페스 바이러스(Herpes Simplex Virus: HSV)는 헤르페스바이러스과에 속하는 바이러스의 일종으로, HSV-1형과 HSV-2형으로 구별되며, 각각 인간 헤르페스바이러스 1형 및 2형으로도 알려져 있다. 핵산은 두 가닥, 선상 DNA이고, 분자량은 96x106 달톤이다.
2015년 미국 FDA 승인을 받은 T-VEC이 악성 흑색종을 대상으로 임상에 사용됨에 따라 헤르페스 바이러스를 기반으로 한 항암 바이러스의 개발이 진행되고 있다. 그러나, 현재 개발된 대부분의 항암 HSV-1은 바이러스 복제에 필요한 유전자가 소실됨에 따라 바이러스 복제가 제한되어 그 치료 효능이 낮다는 한계점이 있다. 또한, HSV-1의 경우 152kb의 크기가 큰 DNA 바이러스이기 때문에 유전자 조작이 용이하지 않다는 문제점이 있다.
따라서, 우수한 암 치료 효능을 가지면서도 유전자 조작이 용이한 재조합 HSV-1 벡터의 개발이 필요하다.
일 양상은 단순 헤르페스 바이러스 1형(HSV-1)의 게놈 영역 중 ICP6 및 IR 영역이 결실된 HSV-1 게놈을 가지는 재조합 HSV-1을 제공한다.
다른 양상은 상기 일 양상에 따른 재조합 HSV-1의 게놈 뉴클레오티드 서열을 포함하는 재조합 HSV-1 벡터를 제공한다.
다른 양상은 상기 일 양상에 따른 재조합 HSV-1을 제조하는 방법을 제공한다.
일 양상은 재조합 단순 헤르페스 바이러스 1형(Herpes Simplex Virus type 1: HSV-1)을 제공한다.
본 발명의 일 양상에 따른 재조합 HSV-1은 HSV-1의 게놈 영역 중 ICP6(Infected-cell protein 6)이 결실되고, UL(Unique Long) 영역과 US(Unique short) 영역 사이의 IR(Internal Repeat) 영역이 결실된 HSV-1 게놈을 가진다. HSV-1의 게놈 영역 중 ICP6 및 IR 영역이 동시에 소실된 벡터 구조는 아직까지 보고된 바 없으므로, 본 발명의 일 양상에 따른 재조합 HSV-1은 신규한 구조의 재조합 바이러스이다. ICP6 및 IR 영역이 결실됨에 따라 약 20 kb의 유전자가 소실된 것이므로, 비교적 큰 크기의 외래 유전자의 삽입 또는 1종 이상의 다양한 외래 유전자의 동시 삽입이 가능하다. 리보뉴클레오티드 환원효소(ribonucleotide reductase)인 ICP6는 HSV-1의 DNA 생합성에 관여하는 효소로서 정상세포에 감염 시 바이러스의 DNA 복제에 필요한 효소이다. 최근 리보뉴클레오티드 환원효소는 다양한 암세포에 과발현되어 있다고 알려져 있다. 따라서 ICP6 유전자를 제거할 경우 정상세포에서는 바이러스의 복제가 제한되는 반면 암세포에서는 바이러스가 활발하게 복제가 가능한 바이러스를 제작할 수 있다. 또한 HSV-1에는 ICP0, ICP34.5, ICP4가 2 카피(copy)씩 존재하며 1 카피만으로도 바이러스의 복제가 가능하다. 따라서 IR 영역에 있는 ICP0, ICP34.5, ICP4의 1 카피를 제거할 경우 바이러스 복제에 어떠한 영향 없이 다양한 크기와 종류의 치료 유전자 삽입이 가능하게 된다. 뿐만 아니라 HSV-1은 IR 영역이 있어서 총 4개의 아이소타입(isotype)의 바이러스를 만들게 되는데 IR 영역을 제거할 경우 단 1개의 HSV-1 아이소타입인 좀더 안정적인 바이러스를 만들 수 있다. 즉, HSV-1 게놈 영역 중 ICP6 유전자를 제거함으로써 암세포 선택성을 부여할 수 있으며, HSV-1 게놈 영역 중 IR 영역을 제거함으로써 HSV-1 항암 바이러스의 구조적 안정성과 더불어 치료 유전자를 삽입할 수 있는 공간 확보가 가능하게 된다.
용어 "결실(deletion)"은 바이러스 게놈 상에 존재하는 유전자를 제거하는 것을 의미한다. 예를 들어, 제한효소를 사용하여 유전자를 제거할 수 있다. 제한효소를 사용하는 유전자 클로닝 방법에 의해 전체 유전자를 제거하거나 유전자 뉴클레오티드 서열의 일부를 제거할 수도 있다. 상기 유전자 결실에 의해 유전자의 기능적 단백질의 발현이 일어나지 않거나 저해된다. 약 20 kb의 크기에 해당하는 ICP6 및 IR 영역을 결실시킴으로써 뉴클레오티드 서열의 길이가 긴 외래 유전자의 삽입이 가능하다.
"단순 헤르페스 바이러스(Herpes Simplex Virus: HSV)"는 헤르페스비리데(Herpesviridae)과에 속하는 바이러스로, 단순 헤르페스 바이러스 1형(Herpes Simplex Virus type 1: HSV-1) 및 단순 헤르페스 바이러스 2형(Herpes Simplex Virus type 2: HSV-2)으로 구분된다. HSV-1은 인간 헤르페스 바이러스 1형(Human Herpes Virus type 1: HHV-1)라고도 한다. HSV-1의 핵산은 이중가닥의 선형 DNA이다. 따라서, HSV-1의 게놈은 이중가닥 선형 DNA로 구성된 것일 수 있다. HSV-1의 게놈 서열은 공지된 HSV-1 균주(strain)의 게놈 서열이라면, 그 종류를 제한하지 않는다. HSV-1 게놈의 예시적인 서열은 NCBI GenBank Accession No. JQ673480.1에 기재되어 있다. 본원에서 별다른 지시가 없는 한 "HSV-1"은 "야생형 HSV-1"와 상호교환적으로 사용되며, 상기 일 양상에 따른 "재조합 HSV-1"와 구별된다.
HSV-1 게놈 영역은 TRL(Terminal Repeat of Long region) 영역, UL(Unique Long) 영역, IRL(Internal Repeat of Long region) 영역, IRS(Internal Repeat of Short region) 영역, US(Unique short) 영역, 및 TRS(Terminal Repeat of Short Region)을 포함하는 것일 수 있다. 상기 UL 영역은 UL1 내지 UL56 유전자의 뉴클레오티드 서열을 포함할 수 있다. 상기 US 영역은 US1 내지 US12 유전자의 뉴클레오티드 서열을 포함할 수 있다. 또한, HSV-1 게놈 영역은 TRL 영역 및 TRS 영역을 포함하지 않는 것일 수 있다. 예를 들어, HSV-1 게놈 영역은 UL 영역, IRL 영역, IRS 영역, 및 US 영역을 포함하는 것일 수 있다.
일 구체예에서, 상기 재조합 HSV-1은 TRL 영역; UL1 내지 UL38 및 UL40 내지 UL56 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 UL 영역; US1 내지 US12 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 US 영역; 및 TRS 영역으로 이루어진 군으로부터 선택되는 HSV-1의 하나 이상의 게놈 영역을 포함할 수 있다. 다른 구체예에서, 상기 재조합 HSV-1은 TRL 영역; UL1 내지 UL38 및 UL40 내지 UL56 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 UL 영역; US1 내지 US12 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 US 영역; 및 TRS 영역으로 이루어진 군으로부터 선택되는 HSV-1의 게놈 영역의 임의의 조합을 포함할 수 있다. 다른 구체예에서, 상기 재조합 HSV-1은 TRL 영역; UL1 내지 UL38 및 UL40 내지 UL56 유전자의 뉴클레오티드 서열을 포함하는 UL 영역; US1 내지 US12 유전자의 뉴클레오티드 서열을 포함하는 US 영역; 및 TRS 영역을 모두 포함할 수 있다.
상기 "TRL(Terminal Repeat of Long region) 영역"은 약 9.2 kb의 크기를 가질 수 있다.
상기 "UL(Unique Long) 영역"은 약 108 kb의 크기를 가질 수 있다. HSV-1의 UL 영역은 UL1 내지 UL56 유전자의 뉴클레오티드 서열을 포함할 수 있다. 본 발명의 일 양상에 따른 재조합 HSV-1은 UL 영역을 포함할 수 있고, 상기 UL 영역은 UL1 내지 UL38 및 UL40 내지 UL56 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함할 수 있다.
상기 "ICP6(Infected-cell protein 6)"은 UL39 유전자일 수 있다. 상기 ICP6의 뉴클레오티드 서열은 약 4.8 kb의 크기를 가질 수 있다. ICP6 유전자의 예시적인 뉴클레오티드 서열은 NCBI GenBank Accession No. JQ673480.1에 기재된 HSV-1 게놈 서열 중 86,364 내지 89,777번째 뉴클레오티드 서열일 수 있다. 일 구체예에서, 상기 재조합 HSV-1의 게놈은 ICP6 유전자의 전부 또는 일부가 결실된 것일 수 있다. 다른 구체예에서, 상기 재조합 HSV-1의 게놈은 야생형 HSV-1 게놈 서열에서 86,901 내지 89,578번째 뉴클레오티드가 결실된 것일 수 있다. 예를 들어, 상기 재조합 HSV-1의 게놈은 HSV-1의 ICP6 유전자의 뉴클레오티드 서열 중 서열번호 1의 뉴클레오티드 서열이 결실된 것일 수 있다. ICP6 단백질의 예시적인 아미노산 서열은 NCBI GenBank Accession No. AFE62867.1에 기재되어 있다.
일 구체예에서, 상기 결실된 IR 영역은 IRL 영역 및 IRS 영역 중 하나 이상의 영역을 포함할 수 있다. 다른 구체예에서, 상기 결실된 IR 영역은 IRL 영역 및 IRS 영역 모두를 포함할 수 있다. 상기 "IRL(Internal Repeat of Long region) 영역"은 약 9.2 kb의 크기를 가질 수 있다. 상기 "IRS(Internal Repeat of Short region) 영역"은 약 6.6 kb의 크기를 가질 수 있다. IRL 영역의 예시적인 뉴클레오티드 서열은 NCBI GenBank Accession No. JQ673480.1에 기재된 HSV-1 게놈 서열 중 117,080 내지 125,845번째 뉴클레오티드 서열일 수 있다. IRS 영역의 예시적인 뉴클레오티드 서열은 NCBI GenBank Accession No. JQ673480.1에 기재된 HSV-1 게놈 서열 중 126,241 내지 132,463번째 뉴클레오티드 서열일 수 있다. 일 구체예에서, 상기 재조합 HSV-1의 게놈은 IR 영역의 전부 또는 일부가 결실된 것일 수 있다. 다른 구체예에서, 상기 재조합 HSV-1의 게놈은 야생형 HSV-1 게놈 서열에서 117,080 내지 131,261번째 뉴클레오티드가 결실된 것일 수 있다. 예를 들어, 상기 재조합 HSV-1의 게놈은 HSV-1의 IR 영역의 뉴클레오티드 서열 중 서열번호 2의 뉴클레오티드 서열이 결실된 것일 수 있다.
일 구체예에서, 상기 재조합 HSV-1은 IR 영역의 전부 또는 일부의 결실과 함께 UL56 유전자의 일부 뉴클레오티드 서열이 추가적으로 결실된 것일 수 있다. UL56 유전자의 예시적인 뉴클레오티드 서열은 NCBI GenBank Accession No. JQ673480.1에 기재된 HSV-1 게놈 서열 중 116,142 내지 116,846번째 뉴클레오티드 서열일 수 있다. 다른 구체예에서, 상기 재조합 HSV-1의 게놈은 야생형 HSV-1 게놈 서열에서 116,200 내지 116,846번째 뉴클레오티드가 결실된 것일 수 있다. 예를 들어, 상기 결실된 UL56 유전자의 일부 뉴클레오티드 서열은 서열번호 3의 뉴클레오티드 서열일 수 있다. 다른 구체예에서, 상기 재조합 HSV-1의 게놈은 야생형 HSV-1 게놈 서열에서 116,200 내지 131,261번째 뉴클레오티드가 결실된 것일 수 있다.
상기 "US(Unique Short) 영역"은 약 13 kb의 크기를 가질 수 있다. HSV-1의 US 영역은 US1 내지 US12 유전자의 뉴클레오티드 서열을 포함할 수 있다. 본 발명의 일 양상에 따른 재조합 HSV-1은 US 영역을 포함할 수 있고, 상기 US 영역은 US1 내지 US12 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함할 수 있다.
상기 "TRS(Terminal Repeat of Short region) 영역"은 약 4 kb의 크기를 가질 수 있다.
상기 재조합 HSV-1의 게놈은 서열번호 4의 뉴클레오티드 서열을 포함할 수 있다.
상기 재조합 HSV-1은 암살상바이러스(oncolytic virus)인 것일 수 있다. 용어 "암살상바이러스"는 "암용해바이러스", "항암 바이러스"와 상호교환적으로 사용된다. 상기 암살상바이러스는 암세포 또는 종양세포를 특이적으로 사멸시킴으로써 암세포의 항원을 노출시켜 면역 세포를 활성화시킬 수 있다. 따라서, 암살상바이러스는 그 자체로 항암 용도로 사용할 수 있으며, 다른 항암제와 병용하여 항암 효과를 증진시킬 수도 있다. 또한, 암살상바이러스 벡터에 다양한 치료 유전자를 삽입하여 항암 효과를 증진시킬 수 있다.
상기 유전자 서열들은 실질적인 동일성(substantial identity) 또는 실질적인 유사성(substantial similarity)을 나타내는 유전자 서열도 포함하는 것으로 해석된다. 상기의 실질적인 동일성은, 상기한 본 발명의 서열과 임의의 다른 서열을 최대한 대응되도록 정렬하고, 당업계에서 통상적으로 이용되는 알고리즘을 이용하여 정렬된 서열을 분석한 경우에, 최소 80%의 상동성, 보다 바람직하게는 90%의 상동성, 가장 바람직하게는 95%의 상동성을 나타내는 서열을 의미한다. 상기의 실질적인 유사성은, 하나 이상의 염기의 결손 또는 삽입과 같은 유전자 서열의 변화가 재조합 바이러스 벡터와의 상동성 재조합을 최소화하는 본 발명의 목적에 영향을 미치지 않는 변화를 총칭한다.
다른 양상은 상기 일 양상에 따른 재조합 HSV-1의 게놈 뉴클레오티드 서열을 포함하는 재조합 HSV-1 벡터를 제공한다.
구체적으로, 단순 헤르페스 바이러스 1형(HSV-1)의 게놈 뉴클레오티드 서열을 포함하는 재조합 HSV-1 벡터에 있어서, 상기 HSV-1의 게놈 뉴클레오티드 서열은 ICP6 이 결실되고, UL(Unique Long) 영역과 US(Unique short) 영역 사이의 뉴클레오티드 서열이 결실된 것인 재조합 HSV-1 벡터를 제공한다.
용어 "바이러스 벡터"는 외래 또는 이종의 유전 정보를 숙주에 전달할 수 있는 바이러스-유래 벡터를 의미한다.
상기 HSV-1, 재조합 HSV-1, ICP6, IR 영역, 및 결실은 상술한 바와 같다.
일 구체예에서, 상기 벡터는 TRL 영역; UL1 내지 UL38 및 UL40 내지 UL56 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 UL 영역; US1 내지 US12 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 US 영역; 및 TRS 영역으로 이루어진 군으로부터 선택되는 HSV-1의 하나 이상의 게놈 영역의 뉴클레오티드 서열을 포함할 수 있다. 다른 구체예에서, 상기 벡터는 TRL 영역; UL1 내지 UL38 및 UL40 내지 UL56 유전자의 뉴클레오티드 서열을 포함하는 UL 영역; US1 내지 US12 유전자의 뉴클레오티드 서열을 포함하는 US 영역; 및 TRS 영역을 모두 포함할 수 있다.
상기 재조합 HSV-1 벡터는 외래 유전자의 뉴클레오티드 서열을 추가적으로 포함할 수 있다. 일 구체예에서, 외래 유전자의 뉴클레오티드 서열은 결실된 ICP6 또는 IR 영역에 삽입될 수 있다. 다른 구체예에서, 삽입할 외래 유전자가 하나를 초과하는 경우, 각 외래 유전자의 뉴클레오티드 서열은 ICP6 및 IR 영역에 각각 삽입될 수 있으나, 이에 한정되지 않는다. 상기 벡터에 의해 운반될 수 있는 외래 유전자는 어떠한 뉴클레오티드 서열도 가능하다. 예를 들어, 상기 벡터에 의해 운반될 수 있는 외래 유전자는 항암 효과를 가지는 유전자일 수 있으나, 이에 한정되지 않는다.
상기 재조합 HSV-1 벡터는 순서대로 TRL 영역, UL 영역, US 영역 및 TRS 영역의 뉴클레오티드 서열을 포함할 수 있으며, ICP6 및 IR 영역이 결실된 것을 특징으로 한다. 일 구체예에서, 상기 재조합 HSV-1 벡터는 도 1C의 유전자 지도를 갖는다. ICP6 및 IR 영역의 뉴클레오티드 서열이 결실된 HSV-1의 게놈 뉴클레오티드 서열을 포함하는 상기 일 양상에 따른 재조합 HSV-1 벡터는 "ΔICP6ΔIR HSV-1 벡터"로 명명하였다.
상기 재조합 HSV-1 벡터는 바이러스 벡터에 통상적으로 포함되는 구성을 추가적으로 포함할 수 있다. 예를 들어, 상기 재조합 HSV-1 벡터는 외래 유전자에 작동 가능하게 연결된 프로모터를 포함할 수 있다. 상기 프로모터의 종류는 당해 기술분야에 공지된 것이라면 어느 것이든 사용할 수 있으며, 그 종류를 한정하지 않는다.
다른 양상은 상기 일 양상에 따른 재조합 HSV-1을 제조하는 방법을 제공한다.
구체적으로, 상기 방법은 ICP6 및 IR 영역이 결실된 HSV-1의 게놈 뉴클레오티드 서열을 포함하는 재조합 HSV-1 벡터를 제조하는 단계; 및 상기 벡터를 세포에 형질감염시켜 재조합 HSV-1를 수득하는 단계를 포함한다.
상기 재조합 HSV-1 벡터는 상술한 바와 같다.
상기 벡터를 세포에 형질감염시키는 방법은 당업계에 공지된 다양한 방법을 통하여 수행할 수 있다. 예를 들어, 미세 주입법(Capecchi, M.R., Cell, 22:479(1980); 및 Harland와 Weintraub, J. Cell Biol. 101:1094-1099(1985)), 칼슘 포스페이트 침전법(Graham, F.L. et al., Virology, 52:456(1973); 및 Chen과 Okayama, Mol. Cell. Biol. 7:2745-2752(1987)), 전기 천공법(Neumann, E. et al., EMBO J., 1:841(1982); 및 Tur-Kaspa et al., Mol. Cell Biol., 6:716-718(1986)), 리포좀-매개 형질감염법(Wong, T.K. et al., Gene, 10:87(1980); Nicolau 및 Sene, Biochim. Biophys. Acta, 721:185-190(1982); 및 Nicolau et al., Methods Enzymol., 149:157-176(1987)), DEAE-덱스트란 처리법 (Gopal, Mol. Cell Biol., 5:1188-1190(1985)), 및 유전자 밤바드먼트(Yang et al., Proc. Natl. Acad. Sci., 87:9568-9572(1990)) 방법에 의해 벡터를 세포에 형질감염시킬 수 있다.
다른 양상은 상기 재조합 HSV-1 또는 재조합 HSV-1 벡터를 포함하는 약학적 조성물을 제공한다.
상기 재조합 HSV-1 및 재조합 HSV-1 벡터는 상술한 바와 같다.
상기 약학적 조성물은 항암용 약학적 조성물일 수 있다.
상기 "암(cancer)"은 세포가 정상적인 성장 한계를 무시하고 분열 및 성장하는 공격적(aggressive) 특성, 주위 조직에 침투하는 침투적(invasive) 특성 및 체내외 다른 부위로 퍼지는 전이적(metastatic) 특성을 갖는 세포에 의한 질병을 총칭한다. 상기 암은 악성 종양(malignant tumor) 혹은 종양(tumor)과 동일한 의미로 사용되며, 고체 종양 및 혈액 종양(blood born tumor)을 포함할 수 있다. 상기 암은 그 종류를 한정하지 않는다.
상기 약학적 조성물은 기존의 암 치료 물질(예: 항암제)과 병용되어 암의 치료 효능을 향상시킬 수 있다. 상기 항암제는 대사길항제, 알킬화제, 토포아이소머라제 길항제, 미세소관 길항제, 항암 항생제, 식물유래 알칼로이드, 항체 항암제 또는 분자표적 항암제일 수 있고, 보다 구체적으로, 탁솔, 나이트로젠 머스타드, 이마티닙, 옥살리플라틴, 리툭시맙, 엘로티닙, 트라스투주맙, 제피티닙, 보르테조밉, 수니티닙, 카보플라틴, 소라페닙, 베바시주맙, 시스플라틴, 세툭시맙, 비스쿰알붐, 아스파라기나제, 트레티노인, 하이드록시카바마이드, 다사티닙, 에스트라머스틴, 겜투주맵오조가마이신, 이브리투모맙튜세탄, 헵타플라틴, 메칠아미노레불린산, 암사크린, 알렘투주맙, 프로카르바진, 알프로스타딜, 질산홀뮴 키토산, 젬시타빈, 독시플루리딘, 페메트렉세드, 테가푸르, 카페시타빈, 기메라실, 오테라실, 아자시티딘, 메토트렉세이트, 우라실, 시타라빈, 플루오로우라실, 플루다라빈, 에노시타빈, 데시타빈, 머캅토푸린, 티오구아닌, 클라드리빈, 카르모퍼, 랄티트렉세드, 도세탁셀, 파클리탁셀, 이리노테칸, 벨로테칸, 토포테칸, 비노렐빈, 에토포시드, 빈크리스틴, 빈블라스틴, 테니포시드, 독소루비신, 이다루비신, 에피루비신, 미톡산트론, 미토마이신, 블레오마이신, 다우노루비신, 닥티노마이신, 피라루비신, 아클라루비신, 페플로마이신, 테모졸로마이드, 부설판, 이포스파미드, 사이클로포스파미드, 멜파란, 알트레트민, 다카바진, 치오테파, 니무스틴, 클로람부실, 미토락톨, 로무스틴 및 카르무스틴일, 이매티닙, 게피티닙, 에르토티닙, 트리스투주맙, 로실레티닙, 네시투무맙, 에버롤리무스, 라무시루맙, 다코미티닙, 포레티닙, 팸브롤리주맙, 이필리무맙, 니볼루맙, 다브라페닙, 벨리파립, 세리티닙, 카무스틴, 시클로포스파미드, 이포스파마이드, 익사베필론, 멜팔란, 메르캅토푸린, 미토산트론, 또는 티에스원일일 수 있으나, 이에 한정되지 않는다.
상기 조성물은 면역 관문 억제제(Immune checkpoint inhibitor)와 동시에, 별도로, 또는 순차적으로 병용 투여될 수 있다. 상기 "면역 관문"은 면역세포 표면에서 면역 반응의 자극 또는 억제 신호를 유발하는데 관여하는 단백질을 총칭하며, 암세포는 이러한 면역 관문을 통해 면역반응의 자극 및 이에 따른 암세포의 억제가 제대로 진행되지 않도록 조작하여 면역체계의 감시망을 회피하게 되며, 즉, 항종양 면역반응을 무력화시킨다. 상기 면역 관문 억제제는 PD-1(programmed cell death-1), PD-L1(programmed cell deathligand 1), PD-L2(programmed cell death-ligand 2), CD27(cluster of differentiation 27), CD28(cluster of differentiation 28), CD70(cluster of differentiation 70), CD80(cluster of differentiation 80; B7-1로도 알려짐), CD86(cluster of differentiation 86; B7-2로도 알려짐), CD137(cluster of differentiation 137), CD276(cluster of differentiation 276), KIRs(killer-cell immunoglobulin-like receptors), LAG3(lymphocyte-activation gene 3), TNFRSF4(tumor necrosis factor receptor superfamily, member 4; CD134로도 알려짐), GITR(glucocorticoid-induced TNFR-related protein), GITRL(glucocorticoid-induced TNFR-related protein ligand), 4-1BBL(4-1BB ligand), 및 CTLA-4(cytolytic T lymphocyte associated antign-4) 길항제 중 하나 이상을 포함할 수 있으나, 이에 한정되지 않는다.
상기 약학적 조성물은 약학적으로 허용가능한 담체 또는 희석제를 더 포함할 수 있다. 약학적으로 허용가능한 담체 또는 희석제는 당업계에 알려진 것일 수 있다. 상기 담체 또는 희석제는 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물(예를 들면, 식염수 및 멸균수), 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘, 미네랄 오일, 링거액, 완충제, 말토덱스트린 용액, 글리세롤, 에탄올, 덱스트란, 알부민, 또는 이들의 임의의 조합일 수 있다. 상기 약학적 조성물은 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 또는 보존제를 더 포함할 수 있다.
상기 약학적 조성물은 당업자에게 알려진 방법에 따라, 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 용매 중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수 있고, 분산제 또는 안정화제를 추가적으로 포함할 수 있다. 상기 수성 용매는 생리식염수 또는 PBS를 포함하는 것일 수 있다. 일 구체예에 따른 상기 약학적 조성물은 경구 또는 비경구 투여 형태, 바람직하게는 비경구 투여 형태로 제제화될 수 있다. 근육내, 복강내, 피하 및 정맥내 투여 형태의 경우, 통상적으로 활성 성분의 멸균 용액을 제조하고, 용액의 pH를 적합하게 조절할 수 있는 완충제를 포함할 수 있으며, 정맥내 투여의 경우 제제에 등장성이 부여되도록 등장화제를 포함할 수 있다.
상기 약학적 조성물의 투여량(유효량)은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성별, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있고, 당업자라면 이러한 요인들을 고려하여 투여량을 적절히 조절할 수 있다. 가능한 투여 경로에는 비경구 (예를 들어, 피하, 근육내, 동맥내, 복강내, 경막내, 또는 정맥내), 국소 (경피 포함), 및 주사, 또는 이식성 장치 또는 물질의 삽입을 포함할 수 있다. 일 구체예에 따른 치료의 대상동물로서는, 인간 및 그 밖의 목적으로 하는 포유동물을 예로 들 수 있고, 구체적으로는 인간, 원숭이, 마우스, 래트, 토끼, 양, 소, 개, 말, 돼지 등이 포함된다.
다른 양상은 개체에 상기 재조합 HSV-1 또는 재조합 HSV-1 벡터, 또는 상기 재조합 HSV-1 또는 재조합 HSV-1 벡터를 포함하는 약학적 조성물의 유효량을 투여하는 단계를 포함하는 암세포 또는 종양세포 생존능을 저해하는 방법을 제공한다. 상기 방법은 암 치료 방법일 수 있다.
용어 "치료"는 질환, 장애 또는 병태, 또는 그의 하나 이상의 증상의 경감, 진행 억제 또는 예방을 지칭하거나, 그를 포함하며, "유효성분" 또는 "약제학적 유효량"은 질환, 장애 또는 병태, 또는 그의 하나 이상의 증상의 경감, 진행 억제 또는 예방에 충분한 본원에서 제공되는 발명을 실시하는 과정에서 이용되는 조성물의 임의의 양을 의미할 수 있다.
용어, "투여하는", "도입하는", 및 "이식하는"은 상호교환적으로 사용되고 일 구체예에 따른 조성물의 원하는 부위로의 적어도 부분적 국소화를 초래하는 방법 또는 경로에 의한 개체내로의 일 구체예에 따른 조성물의 배치를 의미할 수 있다. 일 구체예에 따른 조성물의 유효성분을 생존하는 개체 내에서 원하는 위치로 전달하는 임의의 적절한 경로에 의해 투여될 수 있다. 개체 투여 후 세포의 생존 기간은 짧으면 수 시간, 예를 들면 24시간 내지 수일 내지 길면 수년일 수 있다.
일 양상에 따른 재조합 HSV-1은 ICP6 및 IR 영역이 동시에 결실됨으로써 비교적 큰 크기의 외래 유전자를 삽입하거나 다양한 외래 유전자를 동시에 삽입할 수 있어 유전자 조작이 용이하다. 또한, 안전하면서도 암세포 살상 효과가 우수한 항암 바이러스로서 암 치료 분야에 다양하게 활용될 수 있다.
도 1A는 야생형 HSV-1의 게놈 모식도이다.
도 1B는 ICP6가 결실된(ΔICP6) HSV-1 게놈 모식도이다.
도 1C는 ICP6 및 IR 영역이 결실된(ΔICP6ΔIR) HSV-1 게놈 모식도이다.
도 2는 rpsL-neo 유전자와 UL56-rpsL-neo 프라이머 및 UsIR-rpsL-neo 프라이머의 위치를 나타낸 모식도이다.
도 3은 ΔICP6-ΔIR-rpsL-neo의 모식도이다.
도 4는 UL55 S 프라이머와 UsIR-rpsL neo AS 프라이머로 PCR을 수행하여 rpsL-neo의 삽입 여부를 확인한 PCR 수행 결과이다. 음성대조군으로 HSV-1 WT를 사용하고, 양성대조군으로 ΔICP6-rpsL-neo를 사용하였다.
도 5는 rpsL neo S 프라이머 및 rpsL neo AS 프라이머로 PCR을 수행하여 rpsL-neo의 삽입 여부를 확인한 PCR 수행 결과이다. 음성대조군으로 HSV-1 WT를 사용하고, 양성대조군으로 ΔICP6-rpsL-neo를 사용하였다.
도 6은 당단백질 C를 검출하는 gC S 프라이머 및 gC AS 프라이머로 PCR을 수행하여 rpsL-neo의 삽입 여부를 확인한 PCR 수행 결과이다. 음성대조군으로 HSV-1 WT를 사용하고, 양성대조군으로 ΔICP6-rpsL-neo를 사용하였다.
도 7은 UL55 S 프라이머 및 ΔIR AS 프라이머로 PCR을 수행하여 ΔICP6ΔIR 바이러스에서 IR가 잘 제거되었는지 확인한 PCR 수행 결과이다. 양성대조군으로 ΔIR 바이러스를 사용하였다.
도 8은 rpsL-neo S 프라이머 및 rpsL-neo AS 프라이머로 PCR을 수행하여 ICP6ΔIR 바이러스에서 외래 유전자 rpsL-neo가 잘 제거되었는지 확인한 PCR 수행 결과이다. 대조군으로 ΔICP6-ΔIR-rpsL-neo를 사용하였다.
도 9는 UL55 S 프라이머 및 rpsL-neo S AS 프라이머로 PCR을 수행하여 ICP6ΔIR 바이러스에서 IR 및 rpsL-neo가 잘 제거되었는지 확인한 PCR 수행 결과이다. 대조군으로 ΔICP6-ΔIR-rpsL-neo를 사용하였다.
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.
실시예 1: ICP6 IR 영역이 결실된 재조합 HSV -1( ΔICP6ΔIR HSV - 1)의 제작
도 1A는 야생형 HSV-1의 게놈 모식도이다. HSV-1 게놈은 크게 UL(Unique Long) 영역과 US(Unique short) 영역으로 나뉜다. UL 영역은 하나의 복제원점과 TR(Terminal repeat)과 IR(Internal repeat)으로 구성된 a 및 b가 5'에 존재하고, 역방향의 a 및 b가 3'에 존재한다. US 영역은 두 개의 복제원점과 역방향의 c 서열이 5'에 존재하고, 뒤쪽에 정방향의 c가 반복되며, 3' 끝에는 a 서열이 한번 더 반복된다.
먼저, 야생형의 HSV-1 WT 바이러스 게놈 서열에서 ICP6 일부 영역이 결손된 ΔICP6 HSV-1 바이러스를 제작하였다. 야생형 HSV-1 게놈 서열에서 86,364부터 89,777 번째 뉴클레오티드는 ICP6 유전자를 코딩하는 서열이다. 이 유전자 중 일부 영역인 86,901 내지 89,578 번째 뉴클레오티드를 당업계에 공지된 방법으로 결손시키고, 이를 ΔICP6 HSV-1 바이러스로 명명하였다.
도 1B는 ICP6가 결실된(ΔICP6) HSV-1 게놈 모식도이다.
다음으로, 상기 ΔICP6 HSV-1 바이러스를 주형으로 하여, ICP6 및 IR 영역이 결손된 ΔICP6ΔIR 바이러스를 제작하였다. 야생형 HSV-1 게놈 서열에서 116,141 내지 116,846 번째 뉴클레오티드는 UL56 서열이며, IR 영역은 크게 b'(117,080 내지 125,845), a'(125,846 내지 126,240), c'(126,241 내지 132,463)으로 구성되어 있다. 이 영역에서 UL56 유전자의 일부 영역에서부터 IR 영역의 일부 영역까지에 해당하는 116,200 내지 131,261 번째 뉴클레오티드를 당업계에 공지된 방법으로 결손시켰다. 이를 ΔICP6ΔIR HSV-1 바이러스로 명명하였다. 도 1C는 ICP6 및 IR 영역이 결실된(ΔICP6ΔIR) HSV-1 게놈 모식도이다.
실시예 2: 외래 유전자 rpsL -neo가 삽입된 ΔICP6 - ΔIR - rpsL -neo의 제작
ICP6 유전자와 IR 유전자가 동시에 소실된 상기 실시예 1의 ΔICP6ΔIR HSV-1에 외래 유전자인 rpsL-neo 유전자 1319 bp를 삽입하여 바이러스를 제작하고, 외래 유전자 삽입 여부를 검증하였다.
구체적으로, 하기 표 1과 같이 UL56과 rpsL-neo에 상보적인 서열을 갖는 UL56-rpsL-neo 프라이머와 UsIR과 rpsL-neo에 상보적인 서열을 갖는 UsIR-rpsL-neo 프라이머를 제작하였다. rpsL-neo 유전자 200ng을 주형으로 10pmol의 UL56-rpsL-neo 프라이머 및 UsIR-rpsL-neo 프라이머 및 2X green master mix(thermo scientific)반응 효소를 사용하여 PCR을 수행하였다. PCR 산물을 상기 실시예 1의 ΔICP6 토탈벡터와 함께 DH10b 대장균에 형질전환시켜 상동재조합(homologous recombination)을 유도하여 rpsL-neo를 발현하는 ΔICP6-ΔIR-rpsL-neo를 제작하였다.
도 2는 rpsL-neo 유전자와 UL56-rpsL-neo 프라이머 및 UsIR-rpsL-neo 프라이머의 위치를 나타낸 모식도이다.
도 3은 ΔICP6-ΔIR-rpsL-neo의 모식도이다.
프라이머 명칭 서열번호 서열
UL56-rpsL-neo 5 5’-acaggaataccagaataatgaccaccacaatcgcgaccaccccaaataca GGCCTGGTGATGATGG
CGGGATCG-3’

(밑줄: UL56에 상보적 서열, 볼드체: rpsL-neo에 상보적 서열)
UsIR-rpsL-neo 6 5’-cccgaggacgccccgatcgtccacacggagcgcggctgccgacacggatc TCAGAAGAACTCGTCAAGAAGGCG-3’

(볼드체: rpsL-neo에 상보적 서열, 밑줄: UsIR에 상보적 서열)
상기 상동재조합의 생성 여부를 검증하기 위하여 하기 표 2의 PCR 프라이머를 사용하여 PCR을 수행하였다. 각각 PCR의 조건은 다음과 같다. 200ng을 주형으로 10 pmol의 UL55 S 프라이머 및 UsIR-rpsL neo AS 프라이머에 2X green master mix(thermo scientific)반응 효소를 첨가한 후 PCR 기계(Bio-rad)에 변성(denature) 95℃ 30초, 어닐링(annealing) 58℃ 30초, 신장(extend) 72℃ 2분의 조건으로 PCR을 수행하였다. rpsL-neo 및 당단백질 C를 확인하기 위해서는 상기와 동일한 혼합물 비율에 변성 95℃ 30초, 어닐링 58℃ 30초, 신장 72℃ 30초의 조건으로 PCR을 수행하였다.
프라이머 명칭 서열번호 서열(5' → 3')
UL55 S 7 ACGCGTCGACtaaaaacaaaacatttcaaacaaatcgcccca
UsIR-rpsL neo AS 8 cccgaggacgccccgatcgtccacacggagcgcggctgccgacacggatcTCAGAAGAACTCGTCAAGAAGGCG
rpsL neo S 9 CGGCATCGCCCTAAAATTCGGCGTCCTC
rpsL neo AS 10 AAGAACCGGGCGCCCCTGCGCTGACAGC
gC S 11 CAGATCCGATGCCGGTTTCGGAATTCCACCCG
gC AS 12 CGGGTTAAACACCTGGCGGTCGTCCTCGAAC
ICP6 R-rpsL-neo S 13 GTTCCTGTCGCGACACACGGCGCCGCTCTGCGGTATTCGGGGGGGAGGGGGGCCTGGTGATGATGGCGGGATCG
ICP6 R-rpsL-neo AS 14 AGGGTCCCGTCCGCCTTCTCCGTGACATACAGGGTCATGGATTGGCTATGTCAGAAGAACTCGTCAAGAAGGCG
도 4는 UL55 S 프라이머와 UsIR-rpsL neo AS 프라이머로 PCR을 수행하여 rpsL-neo의 삽입 여부를 확인한 PCR 수행 결과이다. 음성대조군으로 HSV-1 WT를 사용하고, 양성대조군으로 ΔICP6-rpsL-neo를 사용하였다. ΔICP6-rpsL-neo는 200ng을 주형으로 10 pmol의 ICP6 R-rpsL-neo S 프라이머 및 ICP6 R-rpsL-neo AS primer 프라이머와 2X green master mix (thermo scientific) 반응 효소를 첨가한 후 PCR 기계(Bio-rad)에 변성 95℃ 30초, 어닐링 58℃ 30초, 신장 72℃ 1분 30초의 조건으로 PCR을 수행하였다. rpsL-neo의 PCR 산물을 야생형 HSV-1 토탈벡터와 함께 DH10b 대장균에 형질전환(transformation)시켜 상동재조합(Homologous recombination)을 유도하여 ΔICP6-rpsL-neo를 제작하였다.그 결과, 제작된 ΔICP6-ΔIR-rpsL-neo에서 양성대조군과 동일한 2300 bp의 밴드를 확인하였으므로, 상동재조합이 성공적으로 이루어졌음을 확인하였다.
도 5는 rpsL neo S 프라이머 및 rpsL neo AS 프라이머로 PCR을 수행하여 rpsL-neo의 삽입 여부를 확인한 PCR 수행 결과이다. 음성대조군으로 HSV-1 WT를 사용하고, 양성대조군으로 ΔICP6-rpsL-neo를 사용하였다. 그 결과, 제작된 ΔICP6-ΔIR-rpsL-neo에서 양성대조군과 동일한 534 bp의 밴드를 확인하였으므로, 상동재조합이 성공적으로 이루어졌음을 확인하였다.
도 6은 당단백질 C를 검출하는 gC S 프라이머 및 gC AS 프라이머로 PCR을 수행하여 rpsL-neo의 삽입 여부를 확인한 PCR 수행 결과이다. 음성대조군으로 HSV-1 WT를 사용하고, 양성대조군으로 ΔICP6-rpsL-neo를 사용하였다. 그 결과, 제작된 ΔICP6-ΔIR-rpsL-neo에서 양성대조군과 동일한 512 bp의 밴드를 확인하였으므로, 상동재조합이 성공적으로 이루어졌음을 확인하였다.
따라서, ΔICP6ΔIR 바이러스에 외래 유전자인 rpsL-neo 유전자가 성공적으로 삽입되었음을 확인하였다.
실시예 3: ΔICP6ΔIR 바이러스의 제작
상기 실시예 2에서 제작된 ΔICP6-ΔIR-rpsL-neo에서 외래 유전자 rpsL-neo를 제거하여 ΔICP6ΔIR 바이러스를 제작하였다.
구체적으로, 하기 표 3의 프라이머를 제작한 후, 서냉복원법(primer annealing)을 수행하여 상보적 서열이 결합한 2가닥의 올리고머를 제작하였다. 제작한 올리고머를 상기 실시예 2의 ΔICP6-ΔIR-rpsL-neo 토탈벡터와 함께 DH10b 대장균에 형질전환시켜 상동재조합을 유도하여 dICP6-dIR을 제작하였다.
프라이머 명칭 서열번호 서열(5' → 3')
ΔIR S 15 ACAGGAATACCAGAATAATGACCACCACAATCGCGACCACCCCAAATACAGATCCGTGTCGGCAGCCGCGCTCCGTGTGGACGATCGGGGCGTCCTCG
ΔIR AS 16 CGAGGACGCCCCGATCGTCCACACGGAGCGCGGCTGCCGACACGGATCTGTATTTGGGGTGGTCGCGATTGTGGTGGTCATTATTCTGGTATTCCTGT
상기 외래 유전자가 제거된 ΔICP6ΔIR 바이러스가 성공적으로 제작되었는지 확인하기 위하여 상기 기재한 PCR 프라이머를 사용하여 PCR을 수행하였다. 200ng을 주형으로 10 pmol의 UL55 S 프라이머 및 ΔIR AS 프라이머에 2X green master mix(thermo scientific) 반응 효소를 첨가한 후 PCR 기계(Bio-rad)에 변성 95℃ 30초, 어닐링 58℃ 30초, 신장 72℃ 1분의 조건으로 PCR을 수행하였다. rpsL-neo를 확인하기 위해서는 상기와 동일한 혼합물 비율에 신장 95℃ 30초, 어닐링 58℃ 30초, 신장 72℃ 30초의 조건으로 PCR을 수행하였다. 도 7은 UL55 S 프라이머 및 ΔIR AS 프라이머로 PCR을 수행하여 ΔICP6ΔIR 바이러스에서 IR가 잘 제거되었는지 확인한 PCR 수행 결과이다. 양성대조군으로 ΔIR 바이러스를 사용하였다.
ΔIR 바이러스는 200ng을 주형으로 10 pmol의 UL56-rpsL-neo 프라이머 및 UsIR-rpsL-neo 프라이머에 2X green master mix(thermo scientific) 반응 효소를 첨가한 후 PCR 기계(Bio-rad)에 변성 95℃ 30초, 어닐링 58℃ 30초, 신장 72℃ 1분의 조건으로 PCR을 수행하였다. rpsL-neo의 PCR 산물을 야생형 HSV-1 토탈벡터와 함께 DH10b 대장균에 형질전환(transformation)시켜 상동재조합(Homologous recombination)을 유도하여 ΔIR-rpsL-neo 바이러스를 제작하였다. 이후 프라이머 ΔIR S과 ΔIR AS를 서냉복원법(primer annealing)수행한 후 ΔIR-rpsL-neo 토탈벡터와 함께 DH10b 대장균에 형질전환(transformation)시켜 상동재조합(Homologous recombination)을 유도하여 ΔIR 바이러스를 제작하였다.
그 결과, 제작된 ΔICP6ΔIR 바이러스에서 양성대조군과 동일한 1 kb 크기의 밴드를 확인하였으므로, IR이 성공적으로 제거되었음을 확인하였다.
도 8은 rpsL-neo S 프라이머 및 rpsL-neo AS 프라이머로 PCR을 수행하여 ICP6ΔIR 바이러스에서 외래 유전자 rpsL-neo가 잘 제거되었는지 확인한 PCR 수행 결과이다. 대조군으로 상기 실시예 2에서 제작된 ΔICP6-ΔIR-rpsL-neo를 사용하였다. 그 결과, 대조군인 ΔICP6-ΔIR-rpsL-neo는 약 500 bp의 밴드를 보이는 것과 달리, ΔICP6ΔIR 바이러스는 밴드가 생성되지 않았으므로, 외래 유전자 rpsL-neo가 성공적으로 제거되었음을 확인하였다.
도 9는 UL55 S 프라이머 및 rpsL-neo S AS 프라이머로 PCR을 수행하여 ICP6ΔIR 바이러스에서 IR 및 rpsL-neo가 잘 제거되었는지 확인한 PCR 수행 결과이다. 대조군으로 상기 실시예 2에서 제작된 ΔICP6-ΔIR-rpsL-neo를 사용하였다. 그 결과, 대조군인 ΔICP6-ΔIR-rpsL-neo는 약 1700 bp의 밴드를 생성한 것과 달리, ΔICP6ΔIR 바이러스는 밴드가 생성되지 않았으므로, IR 및 외래 유전자가 성공적으로 제거되었음을 확인하였다.
따라서, 외래 유전자가 제거된 ΔICP6ΔIR 바이러스가 성공적으로 제작되었음을 확인하였다.
SEQUENCE LISTING <110> SUNGKWANG MEDICAL FOUNDATION <120> Recombinant herpes simplex virus and method for manufacturing the same <130> PN122407 <160> 16 <170> PatentIn version 3.2 <210> 1 <211> 2678 <212> DNA <213> deleted ICP6 <400> 1 gatcccgtcg gccccgcgga gttcgtctcg gacgaccggt cgtccgattc cgactcggat 60 gactcggagg acaccgactc ggagacgctg tcacacgcct cctcggacgt gtccggcggg 120 gccacgtacg acgacgccct tgactccgat tcgtcatcgg atgactccct gcagatagat 180 ggccccgtgt gtcgcccgtg gagcaatgac accgcgcccc tggatgtttg ccccgggacc 240 cccggcccgg gcgccgacgc cggtggtccc tcagcggtag acccacacgc accgacgcca 300 ggggccggcg ctggtcttgc ggccgatccc gccgtggccc gggacgacgc ggaggggctt 360 tcggaccccc ggccacgtct gggaacgggc acggcctacc ccgtccccct ggaactcacg 420 cccgagaacg cggaggccgt ggcgcgcttt ctgggagatg ccgtgaaccg cgaacccgcg 480 ctcatgctgg agtacttttg ccggtgcgcc cgcgaggaaa ccaagcgtgt cccccccagg 540 acattctgca gcccccctcg cctcacggag gacgactttg ggcttctcaa ctacgcgctc 600 gtggagatgc agcgcctgtg tctggacgtt cctccggtcc tgccgaacgc atacatgccc 660 tattatctca gggagtatgt gacgcggctg gtcaacgggt tcaagccgct ggtgagccgg 720 tccgctcgcc tttaccgcat cctgggggtt ctggtgcacc tgcggatccg gacccgggag 780 gcctcctttg aggagtggct gcgatccaag gaagtggccc tggactttgg cctgacggaa 840 aggcttcgcg agcacgaagc ccagctggtg atcctggccc aggctctgga ccattacgac 900 tgtctgatcc acagcacacc gcacacgctg gtcgagcggg ggctgcaatc ggccctgaag 960 tatgaggagt tttacctaaa gcgctttggc gggcactaca tggagtccgt cttccagatg 1020 tacacccgca tcgccggctt tttggcctgc cgggccacgc gcggcatgcg ccacatcgcc 1080 ctggggcgag aggggtcgtg gtgggaaatg ttcaagttct ttttccaccg cctctacgac 1140 caccagatcg taccgtcgac ccccgccatg ctgaacctgg ggacccgcaa ctactacacc 1200 tccagctgct acctggtaaa cccccaggcc accacaaaca aggcgaccct gcgggccatc 1260 accagcaacg tcagcgccat cctcgcccgc aacgggggca tcgggctatg cgtgcaggcg 1320 tttaacgact ccggccccgg gaccgctagc gtcatacccg ccctcaaggt cctcgactcg 1380 ctggtggcgg cgcacaacaa agagagcgcg cgtccaaccg gcgcgtgcgt gtacctggag 1440 ccgtggcaca ccgacgtgcg ggccgtgctc cggatgaagg gggtcctcgc cggcgaagag 1500 gcccagcgct gcgacaatat cttcagcgcc ctctggatgc cagacctgtt tttcaagcgc 1560 ctgattcgcc acctggacgg cgagaagaac gtcacatgga ccctgttcga ccgggacacc 1620 agcatgtcgc tcgccgactt tcacggggag gagttcgaga agctctacca gcacctcgag 1680 gtcatggggt tcggcgagca gatacccatc caggagctgg cctatggcat tgtgcgcagt 1740 gcggccacga ccgggagccc cttcgtcatg ttcaaagacg cggtgaaccg ccactacatc 1800 tacgacaccc agggggcggc catcgccggc tccaacctct gcaccgagat cgtccatccg 1860 gcctccaagc gatccagtgg ggtctgcaat ctgggaagcg tgaatctggc ccgatgcgtc 1920 tccaggcaga cgtttgactt tgggcggctc cgcgacgccg tgcaggcgtg cgtgctgatg 1980 gtgaacatca tgatcgacag cacgctacaa cccacgcccc agtgcacccg cggcaacgac 2040 aacctgcggt ccatgggaat cggcatgcag ggcctgcaca cggcctgcct gaagctgggg 2100 ctggatctgg agtctgtcga atttcaggac ctgaacaaac acatcgccga ggtgatgctg 2160 ctgtcggcga tgaagaccag caacgcgctg tgcgttcgcg gggcccgtcc cttcaaccac 2220 tttaagcgca gcatgtatcg cgccggccgc tttcactggg agcgctttcc ggacgcccgg 2280 ccgcggtacg agggcgagtg ggagatgcta cgccagagca tgatgaaaca cggcctgcgc 2340 aacagccagt ttgtcgcgct gatgcccacc gccgcctcgg cgcagatctc ggacgtcagc 2400 gagggctttg cccccctgtt caccaacctg ttcagcaagg tgacccggga cggcgagacg 2460 ctgcgcccca acacgctcct gctaaaggaa ctggaacgca cgtttagcgg gaagcgcctc 2520 ctggaggtga tggacagtct cgacgccaag cagtggtccg tggcgcaggc gctcccgtgc 2580 ctggagccca cccaccccct ccggcgattc aagaccgcgt ttgactacga ccagaagttg 2640 ctgatcgacc tgtgtgcgga ccgcgccccc tacgtcga 2678 <210> 2 <211> 14182 <212> DNA <213> deleted IR <400> 2 cccctctccc cccctctccc ctctcccccc ctctcccctc tccccccctc tcccctctcc 60 ccccctctcc cctctccccc cctctcccct ctccccccct ctcccctctc cccccctctc 120 ccctctcccc ccctctcccc tctccccccc tctcccctct ccccccctct cccctgctct 180 ttccccgtga cacccgacgc tggggggcgt ggctgccggg aggggccgcg tatgggcggg 240 cctactcggt ctcccgcccc cccgaaccgc cccgccggct ttgcccccct ttgatcccct 300 gctaccccca ccccgtgctc gtggtgcggg gtggggggat gtgggcgggg gtgcgcggga 360 ggtgtcggtg gtgggggtgg tggtggtggt ggtagtagga atggtggtgg gggggagggc 420 gctggttggt caaaaaaggg agggacgggg gccggcagac cgacggcgac aacgctcccc 480 ggcggccggg tcgcggctct tacgagcggc ccggcccgcg ctcccacccc ccgggccgtg 540 tccttgcttt ccccccgtct ccccccccgc cttctcctcc tcctcctcgt ttttccaaac 600 cccgcccacc cggcccggcc cggcccggcc cggccaccgc cgcccaccca cccacctcgg 660 gatacccagc cccggtcccc cgttccccgg gggccgttat ctccagcgcc ccgtccggcg 720 cgccgccccc cgccgctaaa ccccatcccg cccccgggac cccacatata agcccccagc 780 cacacgcaag aacagacacg cagaacggct gtgtttattt taaataaacc gatgtcggaa 840 taaacaaaca caaacacccg cgacgggggg acggagggga cggagggagg ggggtgacgg 900 gggacggaaa cagacacaaa aaacaaccac aaaaaacaac cacccaccga cacccccacc 960 ccagtctcct cgccttctcc cacccacccc acgcccccac tgagcccggt cgatcgacga 1020 gcacccccgc ccacgccccc gcccctgccc cggcgacccc cggcccgcac gatcccgaca 1080 acaataacaa ccccaacgga aagcggcggg gtgttggggg aggcgaggaa caaccgaggg 1140 gaacggggga tggaaggacg ggaagtggaa gtcctgatac ccatcctaca cccccctgcc 1200 ttccaccctc cggccccccg cgagtccacc cgccggccgg ctaccgagac cgaacacggc 1260 ggccaccgcc gccgccgccg ccgacaccgc agagccggcg cgcgcacaca caagcggcag 1320 aggcagaaag gccccgagtc attgtttatg tggccgcggg ccagcagacg gcccgcgaca 1380 cccccccccg cccgtgtggg tatccggccc cccgccccgc gccggtccat taagggcgcg 1440 cgtgcccgcg agatatcaat ccgttaagtg ctctgcagac aggggcaccg cgcccggaaa 1500 tccattaggc cgcagacgag gaaaataaaa ttacatcacc tacccatgtg gtgctgtggc 1560 ctgtttttgc tgcgtcatct gagcctttat aaaagcgggg gcgcggccgt gccgatcgcc 1620 ggtggtgcga aagactttcc gggcgcgtcc gggtgccgcg gctctccggg cccccctgca 1680 gccggggcgg ccaaggggcg tcggcgacat cctcccccta agcgccggcc ggccgctggt 1740 ctgttttttc gttttccccg tttcgggggt ggtgggggtt gcggtttctg tttctttaac 1800 ccgtctgggg tgtttttcgt tccgtcgccg gaatgtttcg ttcgtctgtc ccctcacggg 1860 gcgaaggccg cgtacggccc gggacgaggg gcccccgacc gcggcggtcc gggccccgtc 1920 cggacccgct cgccggcacg cgacgcgaaa aaggcccccc ggaggctttt ccgggttccc 1980 ggcccggggc ctgagatgaa cactcggggt taccgccaac ggccggcccc cgtggcggcc 2040 cggcccgggg ccccggcgga cccaaggggc cccggcccgg ggccccacaa cggcccggcg 2100 catgcgctgt ggtttttttt tcctcggtgt tctgccgggc tccgtcgcct ttcctgttct 2160 cgcttctccc cccccccctt cacccccagt accctcctcc ctcccttcct cccccgttat 2220 cccactcgtc gagggcgccc cggtgtcgtt caacaaagac gccgcgtttc caggtaggtt 2280 agacacctgc ttctccccaa tagagggggg gggacccaaa cgacaggggg cgccccagag 2340 gctaaggtcg gccacgccac tcgcgggtgg gctcgtgtta cagcacacca gcccgttatt 2400 ttccccccct cccaccctta gttagactct gttacttacc cgtccgacca ccaactgccc 2460 ccttatctaa gggccggctg gaagaccgcc agggggtcgg ccggtgtcgc tgtaaccccc 2520 cacgccaatg acccacgtac tccaagaagg catgtgtccc accccgcctg tgtttttgtg 2580 cctggctctc tatgcttggg tcttactgcc tggggggggg gagtgcgggg gagggggggg 2640 gtgtggaagg aaatgcacgg cgcgtgtgta ccccccccta aagttgttcc taaagcgagg 2700 atatggagga gtggcgggtg ccgggggacc ggggtgatct ctggcacgcg ggggtgggaa 2760 gggtcggggg agggggggat ggggtaccgg cccacctggc cggcgcgggt gcgcgtgcct 2820 ttgcacacca accccacgtc ccccggcggt ctctaagaaa caccgccccc cctccttcat 2880 accaccgagc atgcctgggt gtgggttggt aaccaacacg cccatcccct cgtctcctgt 2940 gattctctgg ctgcaccgca ttcttgtttt ctaactatgt tcctgtttct gtctcccccc 3000 ccacccctcc gccccacccc ccaacaccca cgtctgtggt gtggccgacc cccttttggg 3060 cgccccgtcc cgccccgcta cccctcccat cctttgttgc cctatagtgt agttaacccc 3120 cccccccgcc ctttgtggcg gccagaggcc aggtcagtcc gggcgggcag gcgctcgcgg 3180 aaacttaaca cccacaccca acccactgtg gttctggctc catgccagtg gcaggatgct 3240 ttcggggatc ggtggtcagg cagcccgggc cgcggctctg tggttaacac cagagcctgc 3300 ccaacatggc acccccactc ccacgcaccc ccactcccac gcacccccac tcccacgcac 3360 ccccactccc acgcaccccc actcccacgc acccccactc ccacgcaccc ccactcccac 3420 gcacccccac tcccacgcac ccccactccc acgcaccccc gcgatacatc caacacagac 3480 agggaaaaga tacaaaagta aacctttatt tcccaacaga cagcaaaaat cccctgagtt 3540 ttttttatta gggccaacac aaaagacccg ctggtgtgtg gtgcccgtgt ctttcacttt 3600 ccacctcccc gacacggatt ggctggtgta gtgggcgcgg ccagagacca cccagcgccc 3660 gacccccccc tccccacaaa cacgggggcg tcccttattg ttttccctcg tcccgggtcg 3720 acgccccctg ctccccggac cacgggtgcc gagaccgcag gctgcggaag tccagggcgc 3780 ccactagggt gccctggtcg aacagcatgt tccccacggg ggtcatccag aggctgttcc 3840 actccgacgc gggggccgtc gggtactcgg ggggcgtcac gtggttaccc gcggtctcgg 3900 ggagcagggt gcggcggctc cagccgggga ccgcggcccg cagccgggtc gccatgtttc 3960 ccgtctggtc caccaggacc acgtacgccc cgatgttccc cgtctccatg tccaggatgg 4020 gcaggcagtc ccccgtgatc gtcttgttca cgtaaggcga cagggcgacc acgctagaga 4080 cccccgagat gggcaggtag cgcgtgaggc cgcccgcggg gacggccccg gaagtctccg 4140 cgtggcgcgt cttccgggca cacttcctcg gcccccgcgg cccagaagca gcgcgggggc 4200 cgagggaggt ttcctcttgt ctccctccca gggcaccgac ggccccgccc gaggaggcgg 4260 aagcggagga ggacgcggcc ccggtggcgg aagaggtggc ccccgcggga gtcggggccg 4320 aggaggaaga ggcggaggag gaagaggcgg aggccgccga ggacgtcagg ggggtcccgg 4380 gccctccctg gccgcgcccc cccggccctg agtcggaggg ggggtgcgtc gccgccctct 4440 tggcccctgc cggcgcgagg gggggacgcg tggactgggg ggaggggttt tcctggcccg 4500 acccgcgcct cttcctcgga cgcaccgccg cctcctgctc gacagaggcg gcggagggga 4560 gcgggggggc gccggagggg gcggcgccgg agggggcggc gccgcgggag ggcccgtgtc 4620 caccctccac gcccggcccc cccgagccgc gcgccaccgt cgcacgcgcc cggcacagac 4680 tctgttcttg gttcgcggcc tgagccaggg acgagtgcga ctggggcaca cggcgcgcgt 4740 ccgcggggcg ggcggccggc tccgccccgg gggccggggc gcgggggccg ggccccggag 4800 gcggcgcccg cacacacggg gccacggccg cgcgggggcg cgcggggccc gacgcggccg 4860 cggacgcggg gggaccgggg cggggggcgg agcctggcat gggcgccgcg gggggcctgt 4920 ggggagaggc cgggggggag tcgctgatca ctatggggtc tctgttgttt gcaagggggg 4980 cgggtctgtt gacaaggggg cccgtccggc ccctcggccg ccccgcctcc gcttcaacaa 5040 ccccaacccc cccggagggg ccagacgccc cccgcggcac cgcggctcgc gactggcggg 5100 agccgccgcc gccgctgctg ttggtggtgg tgttagtgtt actgctgccg tgtggcccga 5160 tgggcgccga ggggggcgct gtccgagccg cggccggctg gggggctgcg tgagacgccc 5220 cgcccgtcac ggggggcgcg gcggcgcctc tgcgtggggg ggcgcggggc gtccggcggg 5280 gggcgggcgg tacgtagtct gctgcaagag acaacggggg gcgcgatcag gttacgcccc 5340 ctccccggcc cgccctttcc tcgcccgccc gcccgcctat tcctccctcc cccccccctc 5400 ctcctcctcc cccagggtcc tcgccgcccc cccgcctcac cgtcgtccag gtcgtcgtca 5460 tcctcgtccg tggtgggctc agggtgggtg ggcgacaggg ccctcaccgt gtgccccccc 5520 agggtcaggt accgcggggc gaaccgctga ttgcccgtcc agataaagtc cacggccgtg 5580 cccgccctga cggcctcctc ggcctccatg cgggtctggg ggtcgttcac gatcgggatg 5640 gtgctgaacg acccgctggg cgtcacgccc actatcaggt acaccagctt ggcgttgcac 5700 agcgggcagg tgttgcgcaa ttgcatccag gttttcatgc acgggatgca gaagcggtgc 5760 atgcacggga aggtgtcgca gcgcaggtgg ggcgcgatct catccgtgca cacggcgcac 5820 acgtcgccct cgtcgctccc cccgtcctct cgaggggggg cgcccccgca actgccgggg 5880 tcttcctcgc ggggggggct cccccccgag accgcccccc catccacgcc ctgcggcccc 5940 agcagccccg tctcgaacag ttccgtgtcc gtgctgtccg cctcggaggc ggagtcgtcg 6000 tcatggtggt cggcgtcccc ccgccccccc acttcggtct ccgcctccga gtcgctgctg 6060 tccggcaggt ctcggtcgca gggaaacacc cagacatccg gggcgggctg aggggaaaaa 6120 agggggggcg ggtaagaatg gggggatttc ccgcgtcaat cagcgcccac gagttccccc 6180 tccccccccg cctcacaaag tcctgccccc ctgctggcct cggaagaggg gggagaaagg 6240 ggtctgcaac caaaggtggt ctgggtccgt cctttggatc ccgacccctc ttcttccctc 6300 ttctcccgcc ctccagacgc accggagtcg ggggtcccac ggcgtccccc aaatatggcg 6360 ggcggctcct ccccaccccc ctagatgcgt gtgagtaagg gggccctgcg tatgagtcag 6420 tggggaccac gccccctaac acggcgaccc cggtccctgt gtgtttgttg tgggggcgtg 6480 tctctgtgta tgagtcaggg gggtcccacg gcgaccccgg gccctgcgtc tgagtcaaag 6540 gggccatgtg taggtgttgg gggtctgtat atataaagtc agggggtcac atggcgaccc 6600 ctaacagggc gaccccggtc cctgtatata tagggtcagg gggttccgcg ccccctaaca 6660 tggcgccccc ggtccctgta tatatagtgt cacggggttc cacgccccct aacatggcgc 6720 cccaacatgg cgcccggctc ccgtgtatga gtgggggtcc cccaacatgg cggccggttc 6780 cagtgtaagg gtcgggggtc ccccaacatg gcgcccccca acatggcgcc ccccaacatg 6840 gcgccccaga catggcgccc ggcccctcac ctcgcgctgg gggcggccct caggccggcg 6900 ggtactcgct ccggggcggg gctccatggg ggtcgtatgc ggctggaggg tcgctgacgg 6960 agggtccctg ggggtcgcaa cgtaggcggg gcttctgtgg tgatgcggag agggggcggc 7020 ccgagtctgc ctggctgctg cgtctcgctc cgagtgccga ggtgcaaatg cgaccagacc 7080 gtcgggccag ggctaactta taccccacgc ctttcccctc cccaaagggg cggcagtgac 7140 gattccccca atggccgcgc gtcccagggg aggcaggccc accgcggggc ggccccgtcc 7200 ccggggacca acccggcgcc cccaaagaat atcattagca tgcacggccc ggcccccgat 7260 ttgggggacc aacccggtgt cccccaaaga accccattag catgcccctc ccgccgacgc 7320 aacaggggct tggcctgcgt cggtgccccg gggcttcccg ccttcccgaa gaaactcatt 7380 accatacccg gaaccccagg ggaccaatgc gggttcattg agcgacccgc gggccaatgc 7440 gcgaggggcc gtgtgttccg ccaaaaaagc aattaacata acccggaacc ccaggggagt 7500 ggttacgcgc ggcgcgggag gcggggaata ccggggttgc ccattaaggg ccgcgggaat 7560 tgccggaagc gggaagggcg gccggggccg cccattaatg agtttctaat taccataccg 7620 ggaagcggaa caaggcctct gcaagttttt aattaccata ccgggaagtg ggcggcccgg 7680 cccactgggc gggagttacc gcccagtggg ccgggccccg acgactcggc ggacgctggt 7740 tggccgggcc ccgccgcgct ggcggccgcc gattggccag tcccgccctc cgagggcggg 7800 cccgcctcgg gggcgggccg gctccaagcg tatatatgcg cggctcctgc catcgtctct 7860 ccggagagcg gcttggtgcg gagctcccgg gagctccgcg gaagacccag gccgcctcgg 7920 gtgtaacgtt agaccgagtt cgccgggccg gctccgcggg ccagggcccg ggcacgggcc 7980 tcgggcccca ggcacggccc gatgaccgcc tcggcctccg ccacccggcg ccggaaccga 8040 gcccggtcgg cccgctcgcg ggcccacgag ccgcggcgcg ccaggcgggc ggccgaggcc 8100 cagaccacca ggtggcgcac ccggacgtgg ggcgagaagc gcacccgcgt gggggtcgcg 8160 ggggtcgcgg gggtcgcggg gggcttcggc gccccctccc cgcccgcgcg tcgcaggcgc 8220 aggcgcgcca ggtgctctgc ggtgacgcgc aggcggaggg cgaggcgcgg cggaaggcgg 8280 aaggggcgtg agggggggtg ggaggggtta gccccgcccc ccgggcccgc gccgggcggt 8340 ggggaccggg ggcggggggc ggcggcggtg ggccgggcct ctggcgccgg ctcgggcggg 8400 gggctgtccg gccagtcgtc gtcgtcgtcg tcggacgcgg actcgggaac gtggagccac 8460 tggcgcagca gcagcgaaca agaaggcggg ggcccactgg cggggggcgg cggcggggcg 8520 gccgcgggcg cgctcctgac cacgggttcc gagttgggcg tggaggttac ctgggactgt 8580 gcggttggga ccgcgcccgt gggcccgggc ggccgggggc ggcgggggcc gcgatggcgg 8640 cggcgggcca tggagacaga gagcgtgccg gggtggtaga gtttgacagg caagcatgtg 8700 cgtgcagagg cgagtagtgc ttgcctgtct aactcgctag tctcggccgc ggggggcccg 8760 ggctgcccgc cgcccgcctt taaagggccg cgcgcgaccc ccggggggtg tgttttgggg 8820 ggggcccgtt tccggggtct ggccgctcct cccccgctcc tccccccgct cctccccccg 8880 ctcctccccc cgctcctccc cccgctcctc cccccgctcc tccccccgct cctccccccg 8940 ctcctccccc cgctcctccc cccgctcctc cccccgctcc tccccccgct cctccccccg 9000 ctcctccccc cgctcctccc cccgctcctc cccccgctcc tcccccgctc ctcccccgct 9060 cccgcggccc cgccccccac gcccgccgcg cgcgcgcacg ccgcccggac cgccgcccgc 9120 cttttttgcg cgcgcgcgcg cccgcggggg gcccgggctg ccacaggtaa aacaacacca 9180 acaaagcacg gcgcaatccg cacgtcacac gtcacgtcat ccaccacacc tgcccaacaa 9240 cacaactcac agcgacaact caccgcgcaa caactcctgt tcctcatcca cacgtcaccg 9300 cgcacctccc gctcctccag acgtaccccg gcgcaacaca ccgctcctgc tacacaccac 9360 cgcccctccc cagccccagc cctccccagc cccagccctc cccggcccca gccctccccg 9420 gccccagccc tccccggccc cagccctccc cggccccagc cctccccggc cccagccctc 9480 cccagcccca gccctcccca gccgcgtccc gcgctccctc gggggggttc gggcatctct 9540 acctcagtgc cgccaatctc aggtcagaga tccaaaccct ccgggggcgc ccgcgcacca 9600 ccaccgcccc tcgccccctc ccgcccctcg ccccctcccg cccctcgccc cctcccgccc 9660 ctcgccccct cccgcccctc gccccctccc gcccctcgcc ccctcccgcc cctcgccccc 9720 tcccgcccct cgccccctcc cgcccctcgc cccctcccgc ccctcgcccc ctcccgcccc 9780 tcgccccctc ccgcccctcg ccccctcccg cccctcgccc cctcccgccc ctcgccccct 9840 cccgcccctc gccccctccc gcccctcgcc ccctcccgcc cctcgccccc tcccgcccct 9900 cgccccctcc cgcccctcgc cccctcccgc ccctcgaata aacaacgcta ctgcaaaact 9960 taatcaggtc gttgccgttt attgcgtctt cgggtttcac aagcgccccg ccccgtcccg 10020 gcccgttaca gcaccccgtc cccctcgaac gcgccgccgt cgtcttcgtc ccaggcgcct 10080 tcccagtcca caacgtcccg tcgcgggggc gtggccaagc ccgcctccgc ccccagcacc 10140 tccacggccc ccgccgccgc cagcacggtg ccgctgcggc ccgtggccga ggcccagcga 10200 atcccgggcg gcgccggcgg cagggccccc gggccgtcgt cgtcgtcgcc gcgcagcacc 10260 agcggggggg cgtcgtcgtc gggctccagc agggcgcggg cgcaaaagtc cctccgcggc 10320 ccgcgccacc gggccgggcc ggcgcgcacc gcctcgcgcc ccagcgccac gtacacgggc 10380 cgcagcggcg cgcccaggcc ccagcgcgcg caggcgcggt gcgagtgggc ctcctcctcg 10440 cagaagtccg gcgcgccggg cgccatggcg tcggtggtcc ccgaggccgc cgcccggccg 10500 tccagcgccg gcagcacggc ccggcggtac tcgcgcgggg acatgggcac cggcgtgtcc 10560 gggccgaagc gcgtgcgcac gcggtagcgc acgttgccgc cgcggcacag gcgcagcggc 10620 ggcgcgtcgg ggtacaggcg cgcgtgcgcg gcctccacgc gcgcgaagac ccccgggccg 10680 aacacgcggc ccgaggccag caccgtgcgg cgcaggtccc gcgccgccgg ccagcgcacg 10740 gcgcactgca cggcgggcag caggtcgcac gccaggtagg cgtgctgccg cgacaccgcg 10800 ggcccgtcgg cgggccagtc gcaggcgcgc acggtgttga ccacgatgag ccgccggtcg 10860 ccggcgctgg cgagcagccc cagaaactcc acggccccgg cgaaggccag gtcccgcgtg 10920 gacagcagca gcacgccctg cgcgcccagc gccgacacgt cgggggcgcc ggtccagttg 10980 cccgcccagg cggccgtgtc cggcccgcac agccggttgg ccagggccgc cagcaggcag 11040 gacagcccgc cgcgctcggc ggaccactcc ggcggccccc ccgaggcccc gccgccggcc 11100 aggtcctcgc ccggcagcgg cgagtacagc accaccacgc gcacgtcctc ggggtcgggg 11160 atctggcgca tccaggccgc catgcggcgc agcgggcccg aggcgcgcag ggggccaaag 11220 aggcggcccc cggcggcccc gtgggggtgg gggttctcgt cgtcgtcgcc gccgcacgcg 11280 gcctgggcgg cgggggcggg cccggcgcac cgcgcggcga tcgaggccag ggcccgcggg 11340 tcaaacatga gggccggtcg ccaggggacg gggaacagcg ggtggtccgt gagctcggcc 11400 acggcgcgcg gggagcagta ggcctccagg gcggcggccg cgggcgccgc cgtgtggctg 11460 ggcccccggg gctgccgccg ccagccgccc agggggtcgg ggccctcggc gggccggcgc 11520 gacagcgcca cggggcgcgg gcgggcctgc gccgcggcgc cccgggccgc cgcgggctgg 11580 gcgggggtgg gctcgggccc cgggggcgtg gaggggggcg cggggagggg ggcgcgggcg 11640 tccgagccgg gggcgtccgc gccgctcttc ttcgtcttcg ggggtcgcgg gccgccgcct 11700 ccgggcggcc gggccgggcc gggactcttg cgcttgcgcc cctcccgcgg cgcggcggag 11760 gcggcggcgg ccgccagcgc gtcggcggcg tccggtgcgc tggccgccgc cgccagcagg 11820 gggcggaggc tctggttctc aaacagcagg tccgcggcgg cggcggccgc ggagctcggc 11880 aggcgcgggt cccgcggcag cgcggggccc agggccccgg cgaccaggct cacggcgcgc 11940 acggcggcca cggcggcctc gctgccgccg gccacgcgca ggtccccgcg caggcgcatg 12000 agcaccagcg cgtcgcgcac gaaccgcagc tcgcgcagcc acgcgcgcag gcggggcgcg 12060 tcggcgtgcg gcggcggcgg ggaagcgggg cccgcgggtc cctccggccg cggggggctg 12120 gcgggccggg ccccggccag ccccgggacg gccgccaggt cgccgtcgaa gccctcggcc 12180 agcgcctcca ggatcccgcg gcaggcggcc aggcactcga cggccacgcg gccggcctgg 12240 gcgcggcgcc cggcgtcggc gtcggcgtgg cgggcggcgt cggggtcgtc gccccccacg 12300 ggggaggcgg gcgcggcgga cagccgcccc agggcggcga ggatccccgc ggcgccgtac 12360 ccggcgggca ccgcgcgctc gcccggtgcg gcggcggcga cggcggcgac cccctcgtca 12420 tctgcgccgg cgccggggct ccccgcggcc cccgtcagcg ccgcgttctc gcgcgccaac 12480 aggggcgcgt aggcgcggcg caggctggtc agcaggaagc ccttctgcgc gcggtcgtat 12540 cggcggctca tggccacggc ggccgccgcg tgcgccaggc cccagccgaa gcggccggcc 12600 gccatggcgt agcccaggtg gggcacggcc cgcgccacgc tgccggtgat gaaggagctg 12660 ctgttgcgcg cggcgcccga gatccggaag caggcctggt ccagcgccac gtccccgggg 12720 accacgcgcg ggttctggag ccaccccatg gcctccgcgt ccggggtgta cagcagccgc 12780 gtgatcaggg cgtactgctg cgcggcgtcg cccagctcgg gcgcccacac ggccgccggg 12840 gcgcccgagg cctcgaaccg gcgtcgcgcc tcctccgcct cgggcgcccc ccagaggccc 12900 gggcggctgt cgcccaggcc gccgtacagc acccgccccg ggggcggggg cccggcgccg 12960 ggccacggct ccccgctgac gtacccgtcg cgatagcgcg cgtagaaggc gccggaggcc 13020 gcgtcggcgt ccagctcgac ccgccggggc tgcccggccg tgaagcggcc cgtggcgtcg 13080 cggccggcca ccgccgcgcg ggcccggcgg cgctcgatgc ggcccgcgga ggccgcgggg 13140 gtcctcgccg ccgcccgggg cttgggcgcg gcctcggaga gggggggtgg cccgggcggg 13200 ggcggcgtcc gcccgggggc ttccggcgcc gcgctcgacg gaccccgccc gacggcccgc 13260 gcctcgcgtg cgtggtcggc cgcgtcgttg ccgtcgtcgt cctcgtcctc gtcggacgac 13320 gaggacgaag aggatgcgga cgacgaggac gaggacccgg agtccgacga ggtcgatgac 13380 gccgatggcc gccgccggcc gtgacgacgt ctccgcggcg gctgggccgg cgggcgcggc 13440 gacaggcggt ccgtggggtc cggatacgcg ccgcgtagcg gggcctcccg ttcgcggccc 13500 cgggccgggg cccggtcgcc ggcggcgtcg gctgcgtcgt cgtactcgtc cccgtcatcg 13560 tcgtcggcta gaaaggcggg ggtccggggc ggcgaggccg cggggtcggg cgtcgggatc 13620 gtccggacgg cctcctctac catggaggcc agcagagcca gctgtcgcga cgagacggcg 13680 tccccggcgt cctcgccggc gtcggtgccc gccgcggggg ccctcccgtc ccgccgggcg 13740 tcgtcgaggt cgtgggggtg gtcggggtcg tggtcggggt cgtccccgcc ctcctccgtc 13800 tccgcgcccc acccgagggc cccccgctcg tcgcggtctg ggctcggggt gggcggcggc 13860 ccgtcggtgg ggcccgggga gccggggcgc tgcttgttct ccgacgccat cgccgatgcg 13920 gggcgatcct ccggggatac ggctgcgacg gcggacgtag cacggtaggt cacctacgga 13980 ctctcgatgg ggggaggggg cgagacccac ggaccccgac gacccccgcc gtcgacgcgg 14040 aactagcgcg gaccggtcga tgcttgggtg gggaaaaagg acagggacgg ccgatccccc 14100 tcccgcgctt cgtccgcgta tcggcgtccc ggcgcggcga gcgtctgacg gtctgtctct 14160 ggcggtcccg cgtcgggtcg tg 14182 <210> 3 <211> 647 <212> DNA <213> deleted UL56 <400> 3 gcatggcgcc acaccacgcc acaacagccc tgtcgccggt atggggcatg atcagacgag 60 ccgcgcgccg cgcgttgggc cctgtacagc tcgcgcgaat tgaccctagg aggccgccac 120 gcgcccgagt tttgcgttcg tcgctggtcg tcgggcgcca aagccccgga cggctgttcg 180 gtcgaacgaa cggccacgac agtggcatag gttggggggt ggtccgacat agcctcggcg 240 tacgtcggga ggcccgacaa gaggtccctt gtgatgtcgg gtggggccac aagcctggtt 300 tccggaagaa acaggggggt tgccaataac ccgccagggc caaaactccg gcgctgcgca 360 cgtcgttcgg cgcggcgccg ggcgcgccga gcggctcgct gggcggcttg gcgtgagcgg 420 ccccgctccg acgcctcgcc ctctccggag gaggttggcg gaattggcac ggacgacagg 480 ggcccagcag agtacggtgg aggtgggtcc gtgggggtgt ccagatcaat aacgacaaac 540 ggcccctcgt tcctaccaga caagctatcg taggggggcg ggggatcagc aaacgcgttc 600 cccgcgctcc atagacccgc gtcgggttgc gccgcctccg aagccat 647 <210> 4 <211> 134271 <212> DNA <213> dIR-dICP6 recombinant HSV-1 <400> 4 gcagcccggg ccccccgcgg gcgcgcgcgc gcgcaaaaaa ggcgggcggc ggtccgggcg 60 gcgtgcgcgc gcgcggcggg cgtggggggc ggggccgcgg gagcggggga ggagcggggg 120 aggagcgggg ggaggagcgg ggggaggagc ggggggagga gcggggggag gagcgggggg 180 aggagcgggg ggaggagcgg ggggaggagc ggggggagga gcggggggag gagcgggggg 240 aggagcgggg ggaggagcgg ggggaggagc ggggggagga gcggggggag gagcgggggg 300 aggagcgggg gaggagcggc cagaccccgg aaacgggccc cccccaaaac acaccccccg 360 ggggtcgcgc gcggcccttt aaaggcgggc ggcgggcagc ccgggccccc cgcggccgag 420 actagcgagt tagacaggca agcactactc gcctctgcac gcacatgctt gcctgtcaaa 480 ctctaccacc ccggcacgct ctctgtctcc atggcccgcc gccgccatcg cggcccccgc 540 cgcccccggc cgcccgggcc cacgggcgcg gtcccaaccg cacagtccca ggtaacctcc 600 acgcccaact cggaacccgt ggtcaggagc gcgcccgcgg ccgccccgcc gccgcccccc 660 gccagtgggc ccccgccttc ttgttcgctg ctgctgcgcc agtggctcca cgttcccgag 720 tccgcgtccg acgacgacga cgacgactgg ccggacagcc ccccgcccga gccggcgcca 780 gaggcccggc ccaccgccgc cgccccccgc ccccggtccc caccgcccgg cgcgggcccg 840 gggggcgggg ctaacccctc ccaccccccc tcacgcccct tccgccttcc gccgcgcctc 900 gccctccgcc tgcgcgtcac cgcagagcac ctggcgcgcc tgcgcctgcg acgcgcgggc 960 ggggaggggg cgccgaagcc ccccgcgacc cccgcgaccc ccgcgacccc cacgcgggtg 1020 cgcttctcgc cccacgtccg ggtgcgccac ctggtggtct gggcctcggc cgcccgcctg 1080 gcgcgccgcg gctcgtgggc ccgcgagcgg gccgaccggg ctcggttccg gcgccgggtg 1140 gcggaggccg aggcggtcat cgggccgtgc ctggggcccg aggcccgtgc ccgggccctg 1200 gcccgcggag ccggcccggc gaactcggtc taacgttaca cccgaggcgg cctgggtctt 1260 ccgcggagct cccgggagct ccgcaccaag ccgctctccg gagagacgat ggcaggagcc 1320 gcgcatatat acgcttggag ccggcccgcc cccgaggcgg gcccgccctc ggagggcggg 1380 actggccaat cggcggccgc cagcgcggcg gggcccggcc aaccagcgtc cgccgagtcg 1440 tcggggcccg gcccactggg cggtaactcc cgcccagtgg gccgggccgc ccacttcccg 1500 gtatggtaat taaaaacttg cagaggcctt gttccgcttc ccggtatggt aattagaaac 1560 tcattaatgg gcggccccgg ccgcccttcc cgcttccggc aattcccgcg gcccttaatg 1620 ggcaaccccg gtattccccg cctcccgcgc cgcgcgtaac cactcccctg gggttccggg 1680 ttatgttaat tgcttttttg gcggaacaca cggcccctcg cgcattggcc cgcgggtcgc 1740 tcaatgaacc cgcattggtc ccctggggtt ccgggtatgg taatgagttt cttcgggaag 1800 gcgggaagcc ccggggcacc gacgcaggcc aagcccctgt tgcgtcggcg ggaggggcat 1860 gctaatgggg ttctttgggg gacaccgggt tggtccccca aatcgggggc cgggccgtgc 1920 atgctaatga tattctttgg gggcgccggg ttggtccccg gggacggggc cgccccgcgg 1980 tgggcctgcc tcccctggga cgcgcggcca ttgggggaat cgtcactgcc gcccctttgg 2040 ggaggggaaa ggcgtggggt ataagttagc cctggcccga cggtctggtc gcatttgcac 2100 ctcggcactc ggagcgagac gcagcagcca ggcagactcg ggccgccccc tctccgcatc 2160 accacagaag ccccgcctac gttgcgaccc ccagggaccc tccgtcagcg accctccagc 2220 cgcatacgac ccccatggag ccccgccccg gagcgagtac ccgccggcct gagggccgcc 2280 cccagcgcga ggtgaggggc cgggcgccat gtctggggcg ccatgttggg gggcgccatg 2340 ttggggggcg ccatgttggg ggacccccga cccttacact ggaaccggcc gccatgttgg 2400 gggaccccca ctcatacacg ggagccgggc gccatgttgg ggcgccatgt tagggggcgt 2460 ggaaccccgt gacactatat atacagggac cgggggcgcc atgttagggg gcgcggaacc 2520 ccctgaccct atatatacag ggaccggggt cgccctgtta ggggtcgcca tgtgaccccc 2580 tgactttata tatacagacc cccaacacct acacatggcc cctttgactc agacgcaggg 2640 cccggggtcg ccgtgggacc cccctgactc atacacagag acacgccccc acaacaaaca 2700 cacagggacc ggggtcgccg tgttaggggg cgtggtcccc actgactcat acgcagggcc 2760 cccttactca cacgcatcta ggggggtggg gaggagccgc ccgccatatt tgggggacgc 2820 cgtgggaccc ccgactccgg tgcgtctgga gggcgggaga agagggaaga agaggggtcg 2880 ggatccaaag gacggaccca gaccaccttt ggttgcagac ccctttctcc cccctcttcc 2940 gaggccagca ggggggcagg actttgtgag gcgggggggg agggggaact cgtgggcgct 3000 gattgacgcg ggaaatcccc ccattcttac ccgccccccc ttttttcccc tcagcccgcc 3060 ccggatgtct gggtgtttcc ctgcgaccga gacctgccgg acagcagcga ctcggaggcg 3120 gagaccgaag tgggggggcg gggggacgcc gaccaccatg acgacgactc cgcctccgag 3180 gcggacagca cggacacgga actgttcgag acggggctgc tggggccgca gggcgtggat 3240 gggggggcgg tctcgggggg gagccccccc cgcgaggaag accccggcag ttgcgggggc 3300 gccccccctc gagaggacgg ggggagcgac gagggcgacg tgtgcgccgt gtgcacggat 3360 gagatcgcgc cccacctgcg ctgcgacacc ttcccgtgca tgcaccgctt ctgcatcccg 3420 tgcatgaaaa cctggatgca attgcgcaac acctgcccgc tgtgcaacgc caagctggtg 3480 tacctgatag tgggcgtgac gcccagcggg tcgttcagca ccatcccgat cgtgaacgac 3540 ccccagaccc gcatggaggc cgaggaggcc gtcagggcgg gcacggccgt ggactttatc 3600 tggacgggca atcagcggtt cgccccgcgg tacctgaccc tgggggggca cacggtgagg 3660 gccctgtcgc ccacccaccc tgagcccacc acggacgagg atgacgacga cctggacgac 3720 ggtgaggcgg gggggcggcg aggaccctgg gggaggagga ggaggggggg gggagggagg 3780 aataggcggg cgggcgggcg aggaaagggc gggccgggga gggggcgtaa cctgatcgcg 3840 ccccccgttg tctcttgcag cagactacgt accgcccgcc ccccgccgga cgccccgcgc 3900 ccccccacgc agaggcgccg ccgcgccccc cgtgacgggc ggggcgtctc acgcagcccc 3960 ccagccggcc gcggctcgga cagcgccccc ctcggcgccc atcgggccac acggcagcag 4020 taacactaac accaccacca acagcagcgg cggcggcggc tcccgccagt cgcgagccgc 4080 ggtgccgcgg ggggcgtctg gcccctccgg gggggttggg gttgttgaag cggaggcggg 4140 gcggccgagg ggccggacgg gcccccttgt caacagaccc gccccccttg caaacaacag 4200 agaccccata gtgatcagcg actccccccc ggcctctccc cacaggcccc ccgcggcgcc 4260 catgccaggc tccgcccccc gccccggtcc ccccgcgtcc gcggccgcgt cgggccccgc 4320 gcgcccccgc gcggccgtgg ccccgtgtgt gcgggcgccg cctccggggc ccggcccccg 4380 cgccccggcc cccggggcgg agccggccgc ccgccccgcg gacgcgcgcc gtgtgcccca 4440 gtcgcactcg tccctggctc aggccgcgaa ccaagaacag agtctgtgcc gggcgcgtgc 4500 gacggtggcg cgcggctcgg gggggccggg cgtggagggt ggacacgggc cctcccgcgg 4560 cgccgccccc tccggcgccg ccccctccgg cgcccccccg ctcccctccg ccgcctctgt 4620 cgagcaggag gcggcggtgc gtccgaggaa gaggcgcggg tcgggccagg aaaacccctc 4680 cccccagtcc acgcgtcccc ccctcgcgcc ggcaggggcc aagagggcgg cgacgcaccc 4740 cccctccgac tcagggccgg gggggcgcgg ccagggaggg cccgggaccc ccctgacgtc 4800 ctcggcggcc tccgcctctt cctcctccgc ctcttcctcc tcggccccga ctcccgcggg 4860 ggccacctct tccgccaccg gggccgcgtc ctcctccgct tccgcctcct cgggcggggc 4920 cgtcggtgcc ctgggaggga gacaagagga aacctccctc ggcccccgcg ctgcttctgg 4980 gccgcggggg ccgaggaagt gtgcccggaa gacgcgccac gcggagactt ccggggccgt 5040 ccccgcgggc ggcctcacgc gctacctgcc catctcgggg gtctctagcg tggtcgccct 5100 gtcgccttac gtgaacaaga cgatcacggg ggactgcctg cccatcctgg acatggagac 5160 ggggaacatc ggggcgtacg tggtcctggt ggaccagacg ggaaacatgg cgacccggct 5220 gcgggccgcg gtccccggct ggagccgccg caccctgctc cccgagaccg cgggtaacca 5280 cgtgacgccc cccgagtacc cgacggcccc cgcgtcggag tggaacagcc tctggatgac 5340 ccccgtgggg aacatgctgt tcgaccaggg caccctagtg ggcgccctgg acttccgcag 5400 cctgcggtct cggcacccgt ggtccgggga gcagggggcg tcgacccggg acgagggaaa 5460 acaataaggg acgcccccgt gtttgtgggg aggggggggt cgggcgctgg gtggtctctg 5520 gccgcgccca ctacaccagc caatccgtgt cggggaggtg gaaagtgaaa gacacgggca 5580 ccacacacca gcgggtcttt tgtgttggcc ctaataaaaa aaactcaggg gatttttgct 5640 gtctgttggg aaataaaggt ttacttttgt atcttttccc tgtctgtgtt ggatgtatcg 5700 cgggggtgcg tgggagtggg ggtgcgtggg agtgggggtg cgtgggagtg ggggtgcgtg 5760 ggagtggggg tgcgtgggag tgggggtgcg tgggagtggg ggtgcgtggg agtgggggtg 5820 cgtgggagtg ggggtgcgtg ggagtggggg tgccatgttg ggcaggctct ggtgttaacc 5880 acagagccgc ggcccgggct gcctgaccac cgatccccga aagcatcctg ccactggcat 5940 ggagccagaa ccacagtggg ttgggtgtgg gtgttaagtt tccgcgagcg cctgcccgcc 6000 cggactgacc tggcctctgg ccgccacaaa gggcgggggg gggggttaac tacactatag 6060 ggcaacaaag gatgggaggg gtagcggggc gggacggggc gcccaaaagg gggtcggcca 6120 caccacagac gtgggtgttg gggggtgggg cggaggggtg gggggggaga cagaaacagg 6180 aacatagtta gaaaacaaga atgcggtgca gccagagaat cacaggagac gaggggatgg 6240 gcgtgttggt taccaaccca cacccaggca tgctcggtgg tatgaaggag ggggggcggt 6300 gtttcttaga gaccgccggg ggacgtgggg ttggtgtgca aaggcacgcg cacccgcgcc 6360 ggccaggtgg gccggtaccc catccccccc tcccccgacc cttcccaccc ccgcgtgcca 6420 gagatcaccc cggtcccccg gcacccgcca ctcctccata tcctcgcttt aggaacaact 6480 ttaggggggg gtacacacgc gccgtgcatt tccttccaca ccccccccct cccccgcact 6540 cccccccccc aggcagtaag acccaagcat agagagccag gcacaaaaac acaggcgggg 6600 tgggacacat gccttcttgg agtacgtggg tcattggcgt ggggggttac agcgacaccg 6660 gccgaccccc tggcggtctt ccagccggcc cttagataag ggggcagttg gtggtcggac 6720 gggtaagtaa cagagtctaa ctaagggtgg gaggggggga aaataacggg ctggtgtgct 6780 gtaacacgag cccacccgcg agtggcgtgg ccgaccttag cctctggggc gccccctgtc 6840 gtttgggtcc ccccccctct attggggaga agcaggtgtc taacctacct ggaaacgcgg 6900 cgtctttgtt gaacgacacc ggggcgccct cgacgagtgg gataacgggg gaggaaggga 6960 gggaggaggg tactgggggt gaaggggggg ggggagaagc gagaacagga aaggcgacgg 7020 agcccggcag aacaccgagg aaaaaaaaac cacagcgcat gcgccgggcc gttgtggggc 7080 cccgggccgg ggccccttgg gtccgccggg gccccgggcc gggccgccac gggggccggc 7140 cgttggcggt aaccccgagt gttcatctca ggccccgggc cgggaacccg gaaaagcctc 7200 cggggggcct ttttcgcgtc gcgtgccggc gagcgggtcc ggacggggcc cggaccgccg 7260 cggtcggggg cccctcgtcc cgggccgtac gcggccttcg ccccgtgagg ggacagacga 7320 acgaaacatt ccggcgacgg aacgaaaaac accccagacg ggttaaagaa acagaaaccg 7380 caacccccac cacccccgaa acggggaaaa cgaaaaaaca gaccagcggc cggccggcgc 7440 ttagggggag gatgtcgccg acgccccttg gccgccccgg ctgcaggggg gcccggagag 7500 ccgcggcacc cggacgcgcc cggaaagtct ttcgcaccac cggcgatcgg cacggccgcg 7560 cccccgcttt tataaaggct cagatgacgc agcaaaaaca ggccacagca ccacatgggt 7620 aggtgatgta attttatttt cctcgtctgc ggcctaatgg atttccgggc gcggtgcccc 7680 tgtctgcaga gcacttaacg gattgatatc tcgcgggcac gcgcgccctt aatggaccgg 7740 cgcggggcgg ggggccggat acccacacgg gcgggggggg gtgtcgcggg ccgtctgctg 7800 gcccgcggcc acataaacaa tgactcgggg cctttctgcc tctgccgctt gtgtgtgcgc 7860 gcgccggctc tgcggtgtcg gcggcggcgg cggcggtggc cgccgtgttc ggtctcggta 7920 gccggccggc gggtggactc gcggggggcc ggagggtgga aggcaggggg gtgtaggatg 7980 ggtatcagga cttccacttc ccgtccttcc atcccccgtt cccctcggtt gttcctcgcc 8040 tcccccaaca ccccgccgct ttccgttggg gttgttattg ttgtcgggat cgtgcgggcc 8100 gggggtcgcc ggggcagggg cgggggcgtg ggcgggggtg ctcgtcgatc gaccgggctc 8160 agtgggggcg tggggtgggt gggagaaggc gaggagactg gggtgggggt gtcggtgggt 8220 ggttgttttt tgtggttgtt ttttgtgtct gtttccgtcc cccgtcaccc ccctccctcc 8280 gtcccctccg tccccccgtc gcgggtgttt gtgtttgttt attccgacat cggtttattt 8340 aaaataaaca cagccgttct gcgtgtctgt tcttgcgtgt ggctgggggc ttatatgtgg 8400 ggtcccgggg gcgggatggg gtttagcggc ggggggcggc gcgccggacg gggcgctgga 8460 gataacggcc cccggggaac gggggaccgg ggctgggtat cccgaggtgg gtgggtgggc 8520 ggcggtggcc gggccgggcc gggccgggcc gggtgggcgg ggtttggaaa aacgaggagg 8580 aggaggagaa ggcggggggg gagacggggg gaaagcaagg acacggcccg gggggtggga 8640 gcgcgggccg ggccgctcgt aagagccgcg acccggccgc cggggagcgt tgtcgccgtc 8700 ggtctgccgg cccccgtccc tccctttttt gaccaaccag cgccctcccc cccaccacca 8760 ttcctactac caccaccacc accaccccca ccaccgacac ctcccgcgca cccccgccca 8820 catcccccca ccccgcacca cgagcacggg gtgggggtag caggggatca aaggggggca 8880 aagccggcgg ggcggttcgg gggggcggga gaccgagtag gcccgcccat acgcggcccc 8940 tcccggcagc cacgcccccc agcgtcgggt gtcacgggga aagagcaggg gagagggggg 9000 gagaggggag agggggggag aggggagagg gggggagagg ggagaggggg ggagagggga 9060 gaggggggga gaggggagag ggggggagag gggagagggg gggagagggg agaggggggg 9120 agaggggaga gggggggaga ggggagaggg ggggagaggg ggtatataaa ccaacgaaaa 9180 gcgcgggaac ggggatacgg ggcttgtgtg gcacgacgtc gtggttgtgt tactgggcaa 9240 acacttgggg actgtaggtt tctgtgggtg ccgaccctag gcgctatggg gattttgggt 9300 tgggtcgggc ttattgccgt tggggttttg tgtgtgcggg ggggcttgtc ttcaaccgaa 9360 tatgttattc ggagtcgggt ggctcgagag gtgggggata tattaaaggt gccttgtgtg 9420 ccgctcccgt ctgacgatct tgattggcgt tacgagaccc cctcggctat aaactatgct 9480 ttgatagacg gtatattttt gcgttatcac tgtcccggat tggacacggt cttgtgggat 9540 aggcatgccc agaaggcata ttgggttaac ccctttttat ttgtggcggg ttttctggag 9600 gacttgagtc accccgcgtt tcctgccaac acccaggaaa cagaaacgcg cttggccctt 9660 tataaagaga tacgccaggc gctggacagt cgcaagcagg ccgccagcca cacacctgtg 9720 aaggctgggt gtgtgaactt tgactattcg cgcacccgcc gctgtgtagg gcgacaggat 9780 ttgggaccta ccaacggaac gtctggacgg accccggttc tgccgccgga cgatgaagcg 9840 ggcctgcaac cgaagcccct caccacgccg ccgcccatca tcgccacgtc ggaccccacc 9900 ccgcgacggg acgccgccac aaaaagcaga cgccgacgac cccactcccg gcgcctctaa 9960 cgatgcctcg acggaaaccc gtccgggttc ggggggcgaa ccggccgcct gtcgctcgtc 10020 agggccggcg ggcgctcctc gccgccctag aggctgtccc gctggtgtga cgttttcctc 10080 gtccgcgccc cccgaccctc ccatggattt aacaaacggg ggggtgtcgc ctgcggcgac 10140 ctcggcgcct ctggactgga ccacgtttcg gcgtgtgttt ctgatcgacg acgcgtggcg 10200 gcccctgatg gagcctgagc tggcgaaccc cttaaccgcc cacctcctgg ccgaatataa 10260 tcgtcggtgc cagaccgaag aggtgctgcc gccgcgggag gatgtgtttt cgtggactcg 10320 ttattgcacc cccgacgagg tgcgcgtggt tatcatcggc caggacccat atcaccaccc 10380 cggccaggcg cacggacttg cgtttagcgt gcgcgcgaac gtgccgcctc ccccgagtct 10440 tcggaatgtc ttggtggccg tcaagaactg ttatcccgag gcacggatga gcggccacgg 10500 ttgcctggaa aagtgggcgc gggacggcgt cctgttacta aacacgaccc tgaccgtcaa 10560 gcgcggggcg gcggcgtccc actctagaat cggttgggac cgcttcgtgg gcggagttat 10620 ccgccggttg gccgcgcgcc gccccggcct ggtgtttatg ctctggggcg cacacgccca 10680 gaatgccatc aggccggacc ctcgggtcca ttgcgtcctc aagttttcgc acccgtcgcc 10740 cctctccaag gttccgttcg gaacctgcca gcatttcctc gtggcgaacc gatacctcga 10800 gacccggtcg atttcaccca tcgactggtc ggtttgaaag gcatcgacgt ccggggtttt 10860 tgtcggtggg ggcttttggg tatttccgat gaataaagac ggttaatggt taaacctctg 10920 gtctcatacg ggtcggtgat gtcgggcgtc gggggagagg gagttccctc tgcgcttgcg 10980 attctagcct cgtggggctg gacgttcgac acgccaaacc acgagtcggg gatatcgcca 11040 gatacgactc ccgcagattc cattcggggg gccgctgtgg cctcacctaa ccaaccttta 11100 cacgggggcc cggaacggga ggccacagcg ccgtctttct ccccaacgcg cgcggatgac 11160 ggcccgccct gtaccgacgg gccctacgtg acgtttgata ccctgtttat ggtgtcgtcg 11220 atcgacgaat tagggcgtcg ccagctcacg gacaccatcc gcaaggacct gcggttgtcg 11280 ctggccaagt ttagcattgc gtgcaccaag acctcctcgt tttcgggaaa cgccccgcgc 11340 caccacagac gcggggcgtt ccagcgcggc acgcgggcgc cgcgcagcaa caaaagcctc 11400 cagatgtttg tgttgtgcaa acgcgcccac gccgctcgag tgcgagagca gcttcgggtc 11460 gttattcagt cccgcaagcc gcgcaagtat tacacgcgat cttcggacgg gcggctctgc 11520 cccgccgtcc ccgtgttcgt ccacgagttc gtctcgtccg agccaatgcg cctccaccga 11580 gataacgtca tgctggcctc gggggccgag taaccgcccc ccccccatgc caccctcact 11640 gcccgtcgcg cgtgtttgat gttaataaat aacacataaa tttggctggt tgtttgttgt 11700 ctttaatgga ccgcccgcaa gggggggggg gcgtttcagt gtcgggtgac gagcgcgatc 11760 cggccgggat cctaggaccc caaaagtttg tctgcgtatt ccagggtggg gctcagttga 11820 atctcccgca gcacctctac cagcaggtcc gcggtgggct ggagaaactc ggccgtcccg 11880 gggcaggcgg ttgtcggggg tggaggcgcg gcgcccaccc cgtgtgccgc gcctggcgtc 11940 tcctctgggg gcgacccgta aatggttgca gtgatgtaaa tggtgtccgc ggtccagacc 12000 acggtcaaaa tgccggccgt ggcgctccgg gcgctttcgc cgcgcgagga gctgacccag 12060 gagtcgaacg gatacgcgta catatgggcg tcccacccgc gttcgagctt ctggttgctg 12120 tcccggccta taaagcggta ggcacaaaat tcggcgcgac agtcgataat caccaacagc 12180 ccaatggggg tgtgctggat aacaacgcct ccgcgcggca ggcggtcctg gcgctcccgg 12240 ccccgtacca tgatcgcgcg ggtgccgtac tcaaaaacat gcaccacctg cgcggcgtcg 12300 ggcagtgcgc tggtcagcga ggccctggcg tggcataggc tatacgcgat ggtcgtctgt 12360 ggattggaca tctcgcggtg ggtagtgagt cccccgggcc gggttcggtg gaactgtaag 12420 gggacggcgg gttaatagac aatgaccacg ttcggatcgc gcagagccga tagtatgtgc 12480 tcactaatga cgtcatcgcg ctcgtggcgc tcccggagcg gatttaagtt catgcgaagg 12540 aattcggagg aggtggtgcg ggacatggcc acgtacgcgc tgttgaggcg caggttgccg 12600 ggcgtaaagc agatggcgac cttgtccagg ctaaggccct gggagcgcgt gatggtcatg 12660 gcaagcttgg agctgatgcc gtagtcggcg tttatggcca tggccagctc cgtagagtca 12720 atggactcga caaactcgct gatgttggtg ttgacgacgg acatgaagcc gtgttggtcc 12780 cgcaagacca cgtaaggcag gggggcctct tccagtaact cggccacgtt ggccgtcgcg 12840 tgccgcctcc gcagctcgtc cgcaaaggca aacacccgtg tgtacgtgta tcccatgagc 12900 gtataattgt ccgtctgcag ggcgacggac atcagccccc cgcgcggcga gccggtcagc 12960 atctcgcagc cccggaagat aacgttgtcc acgtacgtgc taaagggggc gacttcaaat 13020 gcctccccga agagctcttg gaggattcgg aatctcccga ggaaggcccg cttcagcagc 13080 gcaaactggg tgtgaacggc ggcggtggtc tccggttccc cgggggtgta gtggcagtaa 13140 aacacgtcga gctgttgttc gtccagcccc gcgaaaataa cgtcgaggtc gtcgtcggga 13200 aaatcgtccg ggcccccgtc ccgcggcccc agttgcttaa aatcaaacgc acgctcgccg 13260 ggggcgcctg cgtcggccat taccgacgcc tgcgtcggca cccccgaaga tttggggcgc 13320 agagacagaa tctccgccgt tagttctccc atgcgggcgt acgcgagggt cctctgggtc 13380 gcatccaggc ccgggcgctg cagaaagttg taaaaggaga taagcccgct aaatatgagc 13440 cgcgacagga acctgtaggc aaactccacc gaagtctccc cctgagtctt tacaaagctg 13500 tcgtcacgca acactgcctc gaaggcccgg aacgtcccac taaacccaaa aaccagtttt 13560 cgcaggcgcg cggtcaccgc gatctggctg ttgaggacgt aagtgacgtc gttgcgggcc 13620 acgaccagct gctgtttgct gtgcacctcg cagcgcatgt gccccgcgtc ctggtcctgg 13680 ctctgcgagt agttggtgat gcggctggcg ttggccgtga gccacttttc aatagtcagg 13740 ccgggctggt gtgtcagccg tcggtattcg tcaaactcct tgaccgacac gaacgtaagc 13800 acggggaggg tgaacacgac gaactccccc tcacgggtca ccttcaggta ggcgtggagc 13860 ttggccatgt acgcgctcac ctctttgtgg gaggagaaca gccgcgtcca gccggggagg 13920 ttggcggggt tggtgatgta gttttccggg acgacgaagc gatccacgaa ctgcatgtgc 13980 tcctcggtga tgggcaggcc gtactccagc accttcatga ggttaccgaa ctcgtgctcg 14040 acgcaccgtt tgttgttaat aaaaatggcc cagctatacg agaggcgggc gtactcgcgc 14100 agcgtgcggt tgcagatgag gtacgtgagc acgttctcgc tctggcggac ggaacaccgc 14160 agtttctggt gctcgaaggt cgactccagg gacgccgtct gcgtcggcga gcccacacac 14220 accaacacgg gccgcaggcg ggccgcgtac tggggggtgt ggtacagggc gttaatcatc 14280 caccagcaat acaccacggc cgtgaggagg tgacgcccaa ggagcccggc ctcgtcgatg 14340 acgatcacgt tgctgcgggt aaaggccggc agcgccccgt gggtggccgg ggccaaccgc 14400 gtcagggcgc cctcggccaa ccccagggtc cgttccaggg cggccagggc gcgaaactcg 14460 ttccgcaact cctcgccccc ggaggcggcc agggcgcgct tcgtgaggtc caaaatcacc 14520 tcccagtagt acgtcagatc tcgtcgctgc aggtcctcca gcgaggcggg gttgctggtc 14580 agggtgtacg ggtactgtcc cagttgggcc tggacgtgat tcccgcgaaa cccaaattca 14640 tgaaagatgg tgttgatggg tcggctgaga aaggcgcccg agagtttggc gtacatgttt 14700 tgggccgcaa tgcgcgtggc gcccgtcacc acacagtcca agacctcgtt gattgtctgc 14760 acgcacgtgc tctttccgga gccagcgttg ccggtgataa gatacaccgc gaacggaaac 14820 tccctgaggg gcaggcctgc gggggactct aaggccgcca cgtcccggaa ccactgcaga 14880 cggggcactt gcgctccgtc gagctgttgt tgcgagagct ctcggatgcg cttaaggatt 14940 ggctgcaccc cgtgcataga cgtaaaattt aaaaaggcct cggccctccc tggaacggct 15000 ggtcggtccc cgggttgctg aaggtgcggc gggccgggtt tctgtccgtc tagctggcgc 15060 tccccgccgg ccgccgccat gaccgcacca cgctcgtggg cccccactac gcgtgcgcgg 15120 ggggacacgg aagcgctgtg ctcccccgag gacggctggg taaaggttca ccccaccccc 15180 ggtacgatgc tgttccgtga gattctccac gggcagctgg ggtataccga gggccagggg 15240 gtgtacaacg tcgtccggtc cagcgaggcg accacccggc agctgcaggc ggcgatcttt 15300 cacgcgctcc tcaacgccac cacttaccgg gacctcgagg cggactggct cggccacgtg 15360 gcggcccgcg gtctgcagcc ccaacggctg gttcgccggt acaggaacgc ccgggaggcg 15420 gatatcgccg gggtggccga gcgggtgttc gacacgtggc ggaacacgct taggacgacg 15480 ctgctggact ttgcccacgg gttggtcgcc tgctttgcgc cgggcggccc gagcggcccg 15540 tcaagcttcc ccaaatatat cgactggctg acgtgcctgg ggctggtccc catattacgc 15600 aagcgacaag aagggggtgt gacgcagggt ctgagggcgt ttctcaagca gcacccgctg 15660 acccgccagc tggccacggt cgcggaggcc gcggagcgcg ccggccccgg gttttttgag 15720 ctggcgctgg ccttcgactc cacgcgcgtg gcggactacg accgcgtgta tatctactac 15780 aaccaccgcc ggggcgactg gctcgtgcga gaccccatca gcgggcagcg cggagaatgt 15840 ctggtgctgt ggcccccctt gtggaccggg gaccgtctgg tcttcgattc gcccgtccag 15900 cggctgtttc ccgagatcgt cgcgtgtcac tccctccggg aacacgcgca cgtctgccgg 15960 ctgcgcaata ccgcgtccgt caaggtgctg ctggggcgca agagcgacag cgagcgcggg 16020 gtggccggtg ccgcgcgggt cgttaacaag gtgttggggg aggacgacga gaccaaggcc 16080 gggtcggccg cctcgcgcct cgtgcggctt atcatcaaca tgaagggcat gcgccacgta 16140 ggcgacatta acgacaccgt gcgtgcctac ctcgacgagg ccggggggca cctgatagac 16200 gccccggccg tcgacggtac cctccctgga ttcggcaagg gcggaaacag ccgcgggtct 16260 gcgggccagg accagggggg gcgggcgccg cagcttcgcc aggccttccg cacggccgtg 16320 gttaacaaca tcaacggcgt gttggagggc tatataaata acctgtttgg aaccatcgag 16380 cgcctgcgcg agaccaacgc gggcctggcg acccaattgc aggagcgcga ccgcgagctc 16440 cggcgcgcaa cagcgggggc cctggagcgc cagcagcgcg cggccgacct ggcggccgag 16500 tccgtgaccg gtggatgcgg cagccgccct gcgggggcgg acctgctccg ggccgactat 16560 gacattatcg acgtcagcaa gtccatggac gacgacacgt acgtcgccaa cagctttcag 16620 cacccgtaca tcccttcgta cgcccaggac ctggagcgcc tgtcgcgcct ctgggagcac 16680 gagctggtgc gctgttttaa aattctgtgt caccgcaaca accagggcca agagacgtcg 16740 atctcgtact ccagcggggc gatcgccgca ttcgtcgccc cctactttga gtcagtgctt 16800 cgggcccccc gggtaggcgc gcccatcacg ggctccgatg tcatcctggg ggaggaggag 16860 ttatgggatg cggtgtttaa gaaaacccgc ctgcaaacgt acctgacaga catcgcggcc 16920 ctgttcgtcg cggacgtcca gcacgcagcg ctgcccccgc ccccctcccc ggtcggcgcc 16980 gatttccggc ccggcgcgtc cccgcggggc cggtccagat cgcggtcgcc cggaagaact 17040 gcgccaggcg cgccggacca gggcgggggc atcgggcacc gggatggccg ccgcgacggc 17100 cgacgatgag gggtcggccg ccaccatcct caagcaggcc atcgccgggg accgcagcct 17160 ggtcgaggcg gccgaggcga ttagccagca gacgctgctc cgcctggcct gcgaggtgcg 17220 ccaggtcggc gaccgccagc cgcggtttac cgccaccagc atcgcgcgcg tcgacgtcgc 17280 gcctgggtgc cggttgcggt tcgttctgga cgggagtccc gaggacgcct atgtgacgtc 17340 ggaggattac tttaagcgct gctgcggcca gtccagttat cgcggcttcg cggtggcggt 17400 cctgacggcc aacgaggacc acgtgcacag cctggccgtg ccccccctcg ttctgctgca 17460 ccggttctcc ctgttcaacc ccagggacct cctggacttt gagcttgcct gtctgctgat 17520 gtacctggag aactgccccc gaagccacgc caccccgtcg acctttgcca aggttctggc 17580 gtggctcggg gtcgcgggtc gccgcacgtc cccattcgaa cgcgttcgct gccttttcct 17640 ccgcagttgc cactgggtcc taaacacact catgttcatg gtgcacgtaa aaccgttcga 17700 cgacgagttc gtcctgcccc actggtacat ggcccggtac ctgctggcca acaacccgcc 17760 ccccgttctc tcggccctgt tctgtgccac cccgacgagc tcctcattcc ggctgccggg 17820 gccgcccccc cgctccgact gcgtggccta taaccccgcc gggatcatgg ggagctgctg 17880 ggcgtcggag gaggtgcgcg cgcctctggt ctattggtgg ctttcggaga ccccaaaacg 17940 acagacgtcg tcgctgtttt atcagttttg ttgaatttta ggaaataaac ccggttttgt 18000 ttctgtggcc tcccgacgga tgcgcgtgtc cttcctccgt cttggtgggt gggtgtctgt 18060 gtatcgcgtc ccatctgtgc ggagaggggg ggcatgtcgg cacgtattcg gacagactca 18120 agcacacacg ggggagcgct cttgtctcag ggcaatgttt ttattggtca aactcaggca 18180 aacagaaacg acatcttgtc gtcaaaggga tacacaaact tccccccctc tccccatact 18240 cccgccagca ccccggtaaa caccaactca atctcgcgca ggatttcgcg caggtgatga 18300 gcgcagtcca cgggggggag cacaaggggc cgcgggtata gatcgacggg gacgccgacc 18360 gactccccgc ctccgggaca gacacgcacg acgcgccgcc agtagtgctc tgcgtccagc 18420 aaggcgccgc cgcggaaggc agtggggggc aaggggtcgc tagcctcaaa gggggacacc 18480 cgaacgctcc agtactccgc gtccaaccgt ttattaaacg cgtccacgat aaggcggtcg 18540 caggcgtcct ccataaggcc ccgggccgtg agtgcgtcct cctccggcac gcctgccgtt 18600 gtcaggccca ggacccgtcg cagcgtgtcg cgtacgaccc cggccgccgt ggtgtacgcg 18660 ggcccgcgga gaggaaatcc cccaagatgg tcagtgttgt cgcgggagtt ccagaaccac 18720 actcccgcct ggttccaggc gactgcgtgg gtgtagacgc cctcgagggc caggcacagt 18780 gggtgccgca gccggaggcc gttggcccta agcacggctc ccacggccgt ctcgatggcc 18840 cgccgggcgt cctcgatcac cccggaagcc gcatccgcgt cttgggggtc cacgttaaag 18900 acaccccaga acgcaccccc atcgcccccg cagaccgcga acttcaccga gctggccgtc 18960 tcctcgatct gcaggcagac ggcggccatt accccaccca ggagctgccg cagcgcaggg 19020 caggcgtcgc acgtgtccgg gaccaggcgc tccaagacgg ccccggccca gggctctgag 19080 ggagcggcca ccaccagcgc gtccagtctt gctaggcccg tccggccgtg ggggtccgcc 19140 agcccgctcc ccccgaggtc ggccagggcc gccaggagct gggcgcgaag tccggggaag 19200 caaaaccgcg ccgtccagac gggcccgacg gccgcgggcg ggtctaacag ttggatgatt 19260 ttagtggcgg gatgccaccg cgccaccgcc tcccgcaccg cgggcaggag gcatccggct 19320 gccgccgagg ccacgccggg ccaggctcgc ggggggagga cgaccctggc ccccaccgcg 19380 ggccaggccc ccaggagcgc ggcgtaagcg gccgcggccc cgcgcaccag gtcccgtgcc 19440 gactcggccg tggccggcac ggtgaacgtg ggccaacccg gaaaccccag gacggcaaag 19500 tacgggacgg gtcccccccg gacctcaaac tcgggcccca gaaaggcaaa gacgggggcc 19560 agggccccgg gggcggcgtg gaccgtggta tgccactgcc ggaaaagggc gacgagcgcc 19620 ggcgcggaga acttctcgcc ggcgcttaca aagtagtcgt aatcgcgggg cagcagcacc 19680 cgtgccgtga ctcgttgcgg gtgcccgcgt ggccgcaggc ccacctcgca cacctcgacc 19740 aggtccccga acgcgccctc cttcttgatc ggcggaaacg caagagtctg gtattcgcgc 19800 gcaaatagcg cggttccggt ggtgatgtta acggtcagcg aagcggcgga cgcgcactgg 19860 ggggtgtcgc gaatggccgc caggcgcgcc cacgccagcc gcgcgtcggg atgctcggca 19920 acgcgcgccg ccagggccat agggtcgatg tcaatgttgg cctccgcgac caggagagcg 19980 gcgcgagggg cggcgggcgg gccccacgac gctctctcaa ctttcaccac cagtcccgtg 20040 cgtgggtccg agccgatacg cagcggggcg aacagggcca ccggcccggt ctggcgctcc 20100 agggccgcca ggacgcacgc gtacagcgcc cgccacagag tcgggttctc caggggctcc 20160 agcggggagg cggccggcgt cgtcgcggcg cgggcggccg ccacgacggc ctggacggag 20220 acgtccgcgg agccgtagaa atcccgcagc tccgtcgcgg tgacggagac ctccgcaaag 20280 cgcgcgcgac cctcccctgc ggcgttgcga catacaaaat acaccagggc gtggaagtac 20340 tcgcgagcgc gggggggcag ccataccgcg taaagggtaa tggcgctgac gctctcctcc 20400 acccacacga tatctgcggt gtccatcgca cggcccctaa ggatcacggg cggtctgtgg 20460 gtcccatgct gccgtgcctg gccgggcccg gtgggtcgcg gaaaccggtg acgggggggg 20520 ggcggttttt ggggttgggg tgggggtggg aaacggcccg ggtccggggg ccaacttggc 20580 ccctcggtgc gttccggcaa cagcgccgcc ggtccgcgga cgaccacgta ccgaacgagt 20640 gcggtcccga gacttatagg gtgctaaagt tcaccgcccc ctgcatcatg ggccaggcct 20700 cggtggggag ctccgacagc gccgcctcca ggatgatgtc agcgttgggg ttggcgctgg 20760 atgagtgcgt gcgcaaacag cgcccccacg caggcacgcg tagcttgaag cgcgcgcccg 20820 caaactcccg cttgtgggcc ataagcaggg cgtacagctg cctgtgggtc cggcaggcgc 20880 tgtggtcgat gtggtgggcg tccaacaacc ccacgattgt ctgtttggtg aggtttttaa 20940 cgcgccccgc cccgggaaac gtctgcgtgc ttttggccat ctgcacgcca aacagttcgc 21000 cccagattat cttgaacagc gccaccgcgt ggtccgtctc gctaacggac ccgcgcgggg 21060 gacagccgct tagggcgtcg gcgacgcgct tgacggcttc ctccgagagc agaagtccgt 21120 cggttacgtt acagtggccc agttcgaaca ccagctgcat gtagcggtcg tagtgggggg 21180 tcagtaggtc cagcacgtca tcggggccga aggtcctccc agatcccccg gccgccgagt 21240 cccaatgcag gcgcgcggcc atggtgctgc acaggcacaa cagctcccag acgggggtta 21300 cgttcagggt ggggggcagg gccacgagct ccagctctcc ggtgacgttg atcgtgggga 21360 tgacgcccgt ggcgtagtgg tcatagatcc gccgaaatat ggcgctgctg cgggtggcca 21420 tgggaacgcg gagacaggcc tccagcaacg ccaggtaaat aaaccgcgtg cgtcccatca 21480 ggctgttgag gttgcgcatg agcgcgacaa tttccgccgg cgcgacatcg gaccggaggt 21540 atttttcgac gaaaagaccc acctcctccg tctcggcggc ctgggccggc agcgacgcct 21600 cgggatcccg gcaccgcagc tcccgtagat cgcgctgggc cctgagggcg tcgaaatgta 21660 cgccccgcaa aaacagacag aagtcctttg gggtcagggt atcgtcgtgt ccccagaagc 21720 gcacgcgtat gcagtttagg gtcagcagca tgtgaaggat gttaaggctg tccgagagac 21780 acgccagcgt gcatctctca aagtagtgtt tgtaacggaa tttgttgtag atgcgcgacc 21840 cccgccccag cgacgtgtcg catgccgacg cgtcacagcg ccccttgaac cggcgacaca 21900 gcaggtttgt gacctgggag aactgcgcgg gccactggcc gcaggaactg accacgtgat 21960 taaggagcat gggcgtaaag acgggctccg agcgcgcccc ggagccgtcc atgtaaatca 22020 gtagctcccc cttgcggagg gtgcgcaccc gtcccaggga ctggtacacg gacaccatgt 22080 ccggtccgta gttcatgggt tttacgtagg cgaacatgcc atcaaagtgc aggggatcga 22140 agctgaggcc cacggttacg accgtcgtgt atataaccac gcggtattgg ccccacgtgg 22200 tcacgtcccc gaggggggtg agcgagtgaa gcaacagcac gcggtccgta aactgacggc 22260 agaaccgggc cacgatctcc gcgaaggaga ccgtcgacga aaaaatgcag atgttatcgc 22320 ccccgccaag gcgcgcttcc agctccccaa agaacgtggc cccccgggcg tccggagagg 22380 cgtccggaga cgggccgctc ggcggcccgg gcgggcgcag ggcagcctgc aggagctcgg 22440 tccccagacg cgggagaaac aggcaccggc gcgccgaaaa cccgggcatg gcgtactcgc 22500 cgaccaccac atgcacgttt ttttcgcccc ggagaccgca caggaagtcc accaactgcg 22560 cgttggcggt tgcgtccatg gcgatgatcc gaggacaggt gcgcagcagg cgtagcatta 22620 acgcatccac gcggcccagt tgctgcatcg ttggcgaata gagctggccc agcgtcgaca 22680 taacctcgtc cagaacgagg acgtcgtagt tgttcagaag gttggggccc acgcgatgaa 22740 ggctttccac ctggacgata agtcggtgga aggggcggtc gttcataatg taattggtgg 22800 atgagaagta ggtgacaaag tcgaccaggc ctgactcagc gaaccgcgtc gccagggtct 22860 gggtaaaact ccgacgacag gagacgacga gcacactcgt gtccggagag tggatcgctt 22920 cccgcagcca gcggatcagc gcggtagttt ttcccgaccc cattggcgcg cggaccacag 22980 tcacgcacct ggccgtcggg gcgctcgcgt tggggaaggt gacgggtccg tgctgctgcc 23040 gctcgatcgt tgttttcggg tgaacccggg gcacccattc ggccaaatcc cccccgtaca 23100 acatccgcgc tagcgatacg ctcgacgtgt actgttcgca ctcgtcgtcc ccaatgggac 23160 gcccggcccc cagaggatct cccgactccg cgccccccac gaaaggcatg accggggcgc 23220 ggacggcgtg gtgggtctgg tgtgtgcagg tggcgacgtt tgtggtctct gcggtctgcg 23280 tcacggggct cctcgtcctg gcctctgtgt tccgggcacg gtttccctgc ttttacgcca 23340 cggcgagctc ttatgccggg gtgaactcca cggccgaggt gcgcgggggt gtagccgtgc 23400 ccctcaggtt ggacacgcag agccttgtgg gcacttatgt aatcacggcc gtgttgttgt 23460 tggccgcggc cgtgtatgcc gtggtcggcg ccgtgacctc ccgctacgac cgcgccctgg 23520 acgcgggccg ccgtctggct gcggcccgca tggccatgcc gcacgccacg ctgatcgccg 23580 gaaacgtctg ctcttggttg ctgcagatca ccgtcctgtt gctggcccat cgcaccagcc 23640 agctggccca cctggtttac gtcctgcact ttgcgtgtct ggtgtatttt gcggcccatt 23700 tttgcaccag gggggtcctg agcgggacgt atctgcgtca ggtgcacggc ctgatggagc 23760 cggccccgac tcatcatcgc gtcgttggcc cggctcgagc cgtgctgaca aacgccttgc 23820 tgttgggcgt cttcctgtgc acggccgacg ccgcggtatc cctgaatacc atcgccgcgt 23880 tcaactttaa tttttcggcc ccgggcatgc tcatatgcct gaccgtgctg ttcgcccttc 23940 tcgtcgtatc gctgttgttg gtggtcgagg gggtgttgtg tcactacgtg cgcgtgttgg 24000 tgggccccca cctgggggcc gtggccgcca cgggcatcgt cggcctggca tgcgagcact 24060 attacaccaa cggctactac gttgtggaga cgcagtggcc gggggcccag acgggagtcc 24120 gcgtcgccct cgccctggtc gccgcctttg ccctcggcat ggccgtgctc cgctgcaccc 24180 gcgcctatct gtatcacagg cggcaccaca ccaaattttt tatgcgcatg cgcgacacgc 24240 gacaccgcgc acattccgcc ctcaagcgcg tacgcagttc catgcgcgga tcgcgagacg 24300 gccgccacag gcccgcaccc ggcagcccgc ccgggattcc cgaatatgcg gaagacccct 24360 acgcgatctc atacggcggc cagctcgacc ggtacggaga ttccgacggg gagccgattt 24420 acgacgaggt ggcggacgac caaaccgacg tattgtacgc caagatacaa cacccgcggc 24480 acctgcccga cgacgagccc atctatgaca ccgttggggg gtacgacccc gagcccgccg 24540 aggaccccgt gtacagcacc gtccgccgtt ggtagctgtt tggttccgtt ttaataaacc 24600 gtttgtgttt aacccgaccg tggtgtatgt ctggtgtgtg gcgtccgatc ccgttactat 24660 caccgttccc cccaaacccc ggcgattgtg ggttttttta aaaacgacac gcgtgcgacc 24720 gtatacagaa cattgttgtt ttttattcgc tatcggacat ggggggtgga aactgggtgg 24780 cggggcaggc gcctccgggg gttcgccggt gagtgtggcg cgagggggga tccgacgaac 24840 gcaggcgctg tctccccggg gcccgcgtaa ccccgcgcat atccgggggc acgtagaaat 24900 taccttcctc ttcggactcg atatccacga cgtcaaagtc gtgggcggtc agcgagacga 24960 cctccccgtc gtcggtgatg aggacgttgt ttcggcagca gcagggccgg gtcccggaga 25020 acgagaggcc catagctcgg cgagcgtgtc gtcgaacgcc aggcggctgc ttcgctgtat 25080 ggccttatag atctccggat cgatgcggac gggggtaatg atcagggcga tcggaacggc 25140 ctggttcggg agaatggacg ccttgctggg tcctgcggcc ccgagagccc cggcgccgtc 25200 ctccaggcgg aacgttacgc cctcctccgc gctagtgcgg tgcctgccga taaacgtcac 25260 cagatgcggg tggggggggc agtcggggaa gtggctgtcg agcacgtagc cctgcaccaa 25320 gatctgctta aagttcgggt gacgggggtt cgcgaagacg ggctcgcggc gtaccagatc 25380 cccggagctc caggacacgg gggagatggt gtggcgtccg aggtcggggg cgccaaacag 25440 aagcacctcc gagacaacgc cgctatttaa ctccaccaag gcccgatccg cggcggagca 25500 ccgccttttt tcgcccgagg cgtgggcctc tgaccaggcc tggtcttgcg tgacgagagc 25560 ctcctccggg ccggggacgc gcccgggcgc gaagtatcgc acgctgggct tcgggatcga 25620 ccggataaat gcccggaacg cctccgggga ccggtgtgcc atcaagtcct cgtacgcgga 25680 ggccgtgggg tcgctggggt ccatggggtc gaaagcgtac ttggcccggc atttgacctc 25740 gtaaaaggcc aggggggtct tggggactgg ggccaagtag ccgtgaatgt cccgaggaca 25800 gacgagaata tccagggacg ccccgaccat ccccgtgtga ccgtccatga ggaccccaca 25860 cgtatgcacg ttctcttcgg cgaggtcgcc gggttcgtgg aagataaagc gccgcgtgtc 25920 ggcgccggcc tcgccgccgt cgtccgcgcg gcccacgcag tagcgaaaca gcaggcttcg 25980 ggccgtcggc tcgttcaccc gcccgaacat caccgccgaa gactgtacat ccggccgcag 26040 gctggcgttg tgcttcagcc actggggcga gaaacacgga ccctgggggc cccagcggag 26100 ggtggatgcg gtcgtgaggc cccgccggag cagggcccat agctggcagt cggcctggtt 26160 ttgcgtggcc gcctcgtaaa accccatgag gggccggggc gccacggcgt ccgcggcggc 26220 cgggggcccg cggcgcgtca ggcgccatag gtgccggccg agtccgcggt ccaccatacc 26280 cgcctcctcg aggaccacgg ccagggaaca cagataatcc aggcgggccc agaggggacc 26340 gatggccaga ggggcgcgga cgccgcgcag caacccgcgc aggtggcgct cgaacgtctc 26400 ggctagtata tgggagggca gcgcgttggg gatcaccgac gccgaccaca tagagtcaag 26460 gtccggggag tcgggatcgg cgtccgggtc gcgggcgtgg gtgcccccag gagatagcgg 26520 aatgtctggg gtcggaggcc ctgaggcgtc agaaagtgcc ggcgacgcgg cccggggctt 26580 ttcgtctgcg gtgtcggtgg cgtgctgatc acgtgggggg ttaacgggcg aatgggagct 26640 cgggtccaca gctgacgtcg tctggggtgg ggggggcagg ggacggaagg tggttgttag 26700 cggaagactg ttagggcggg ggcgcttggg ggggctgtcg gggccacgag gggtgtcctc 26760 ggccagggcc caggaacgct tagtcacggt gcgtcccggc ggacatgctg ggcctcccgt 26820 ggactccatt tccgagacga cgtgggggga gcggtggttg agcgcgccgc cgggtgaacg 26880 ctgattctca cgacagcgcg tgccgcgcgc acgggttggt gtgacacagg cgggacacca 26940 gcaccaggag aggcttaagc tcgggaggca gcgccaccga cgacagtatc gccttgtgtg 27000 tgtgctggta atttatacac cgatccgtaa acgcgcgccg aatcttggga ttgcggaggt 27060 ggcgccggat gccctctggg acgtcatacg ccaggccgtg ggtgttggtc tcggccgagt 27120 tgacaaacag ggctgggtgc agcacgcggc gataggcgag cagggccagg gcgaagtcca 27180 gcgacagctg gttgttgaaa tactggtaac cgggaaaccg ggtcacgggt acgcccaggc 27240 tcggggcgac gtacacgcta accaccaact ccagcagcgt ctggccaagg gcgtacaggt 27300 caaccgctaa cccgacgtcg tgcttcaggc ggtggttggt aaattcggcc cgttcgttgt 27360 taaggtattt caccaacagc tccgggggct ggttataccc gtgacccacc agggtgtgaa 27420 agttggctgt ggttagggcg gtgggcatgc caaacatccg gggggacttg aggtccggct 27480 cctggaggca aaactgcccc cgggcgatcg tggagttgga gttgagggtg acgaggctaa 27540 agtcggcgag gacggcccgc cggagcgaga cggcgtccga ccgcagcatg acgaggatgt 27600 tggcgcactt gatatccagg tggctgatcc cgcaggtggt gtttaaaaac acaacggcgc 27660 gggccagctc cgtgaagcac tggtggaggg ccgtcgagac cgaggggttt gttgtgcgca 27720 gggacgccag ttggccgata tacttaccga ggtccatgtc gtacgcgggg aacactatct 27780 gtcgttgttg cagcgagaac ccgaggggcg cgatgaagcc gcggatgttg tgggtgcggc 27840 cggcgcgtag agcgcactcc ccgaccaaca gggtcgcgat gagctcaacg gcaaaccact 27900 ccttttcctt tatggtctta acggcaagct tatgttcgcg aatcagttgg acgtcgccgt 27960 atcccccaga ccccccgaag cttcgggccc cggggatctc gagggtcgtg tagtgtaggg 28020 cggggttgat ggcgaacacg gggctgcata gcttgcggat gcgcgtgagg gtaaggatgt 28080 gcgaggggga cgaggggggt gcggttaacg ccgcctggga tctgcgcagg ggcgggcggt 28140 tcagtttggc cgccgtaccg ggcgtctcgg gggacgcgcg gcgatgagac gagcggctca 28200 ttcgccatcg ggatagtccc gcgcgaagcc gctcgcggag gccggatcgg tggcgggacc 28260 cgtgggagga gcgggagccg gcggcgtcct ggagagaggg gccgctgggg cgcccggagg 28320 ccccgtgtgg gttggagtgt atgtaggatg cgagccaatc cttgaaggac tgttggcgtg 28380 caccttgggg gctgaggtta gctgccacat gaccagcagg tcgctgtctg cgggactcat 28440 ccatccttcg gccaggtcgc cgtcttccca cagagaagcg ttggtcgctg cttcctcgag 28500 ttgctcctcc tggtccgcaa gacgatcgtc cacggcgtcc aggcgctcac caagcgccgg 28560 atcgaggtac cgtcggtgtg cggttagaaa gtcacgacgc gccgcttgct cctccacgcg 28620 aattttaaca caggtcgcgc gctgtcgcat catctctaag cgcgcgcggg actttagccg 28680 cgcctccaat tccaagtggg ccgcctttgc agccataaag gcgccaacaa accgaggatc 28740 ttgggtgctg acgccctccc ggtgcagctg cagggtctgg tccttgtaaa tctcggctcg 28800 gaggtgcgtc tcggccaggc gtcggcgcag ggccgcgtgg gcggcatctc ggtccattcc 28860 gccaccctgc gggcgacccg gggggtgctc tgatagtctc gcgtgcccaa ggcccgtgat 28920 cggggtactt cgccgccgcg acccgccacc cggtgtgcgc gatgtttggt cagcagctgg 28980 cgtccgacgt ccagcagtac ctggagcgcc tcgagaaaca gaggcaactt aaggtgggcg 29040 cggacgaggc gtcggcgggc ctcacaatgg gcggcgatgc cctacgagtg ccctttttag 29100 atttcgcgac cgcgaccccc aagcgccacc agaccgtggt cccgggcgtc gggacgctcc 29160 acgactgctg cgagcactcg ccgctcttct cggccgtggc gcggcggctg ctgtttaata 29220 gcctggtgcc ggcgcaacta aaggggcgtg atttcggggg cgaccacacg gccaagctgg 29280 aattcctggc ccccgagttg gtacgggcgg tggcgcgact gcggtttaag gagtgcgcgc 29340 cggcggacgt ggtgcctcag cgtaacgcct actatagcgt tctgaacacg tttcaggccc 29400 tccaccgctc cgaagccttt cgccagctgg tgcactttgt gcgggacttt gcccagctgc 29460 ttaaaacctc cttccgggcc tccagcctca cggagaccac gggcccccca aaaaaacggg 29520 ccaaggtgga cgtggccacc cacggccgga cgtacggcac gctggagctg ttccaaaaaa 29580 tgatccttat gcacgccacc tactttctgg ccgccgtgct cctcggggac cacgcggagc 29640 aggtcaacac gttcctgcgt ctcgtgtttg agatccccct gtttagcgac gcggccgtgc 29700 gccacttccg ccagcgcgcc accgtgtttc tcgtcccccg gcgccacggc aagacctggt 29760 ttctagtgcc cctcatcgcg ctgtcgctgg cctcctttcg ggggatcaag atcggctaca 29820 cggcgcacat ccgcaaggcg accgagccgg tgtttgagga gatcgacgcc tgcctgcggg 29880 gctggttcgg ttcggcccga gtggaccacg ttaaagggga aaccatctcc ttctcgtttc 29940 cggacgggtc gcgcagtacc atcgtgtttg cctccagcca caacacaaac gtaagtcctc 30000 ttttctttcg catggctctc ccaaggggcc ccgggtcgac ccgacccaca cccacccacc 30060 cacccacata cacacacaac cagacgcggg aggaaagtct gccccgtggg cactgatttt 30120 tattcgggat cgcttgagga ggcccgggca acggcccggg caacggtggg gcaactcgta 30180 gcaaataggc gactgatgta cgaagagaag acacacaggc gccacccggc gctggtcggg 30240 gggatgttgt ccgcgccgca ccgtcccccg acgacctctt gcagacggtc cgtgatgcaa 30300 ggacggcggg gggcctgcag cagggtgacc gtatccacgg gatggccaaa gagaagcgga 30360 cacaggctag catccccctg gaccgccagg gtacactggg ccatcttggc ccacagacac 30420 ggggcgacgc agggacagga ctccgttacg acggaggaga gccacagtgc gttggcggaa 30480 tcgatgtggg gcggcggggc gcaggactcg cagccccccg ggtggttggt gatcctggcc 30540 aggagccatc ccagatggcg ggccctgctt cccggtggac agagcgaccc caggtcgctg 30600 tccatggccc agcagtagat ctggccgctg gggaggtgcc accaggcccc cgggcccaag 30660 gcgcaacacg cgcccggctc cgggggggtc ttcgcgggga ccagatacgc gccatccagc 30720 tcgccgacca ctggctcctc cgcgagctgt tcggtggttg ggtcgggggt ttcctccggg 30780 ggggtggccg cccgtatgcg ggcgaacgtg agggtgcaca ggagcggggt cagggggtgc 30840 gtcacgctcc ggaggtggac gatcgcgcag tagcggcgct cgcggttaaa gaaaaagagg 30900 gcaaagaagg tgttcggggg caaccgcagc gccttggggc gcgtcagata cagaaaaatc 30960 tcgcagaaga gggcgcgccc ggggtctggg ttaggaaggg ccacctgaca cagaggctcg 31020 gtgaggaccg ttagacaccg aaagatcttg agccgctcgt ccgcccgaac gacgcgccac 31080 acaaagacgg agttgacaat gcgcgcgata gagtcgacgt ccgtccccag gtcgtcgact 31140 ctgtcgcgcg tgccgcgagc tccggcccgg gaatccggcc ggggcaaggt ccccggggga 31200 ccaggcggcg ccaggggccg ccggggtccc agctgcgcca tgccgggggc ggggggaggg 31260 caaaccccag aggcgggggc caacggcgcg gggaggagtg ggtgggcgag gtggccgggg 31320 gaaggcgccc gctagcgaga acggccgttc ccggacgaca ccttgcgaca aaacctaagg 31380 acagcggccc gcgcgacggg gtccgagagg ctaaggtagg ccgcgatgtt aatggtgaac 31440 gcaaagccgc cgggaaagac aactatgcca cagaggcggc gattaaaccc caggcagagg 31500 taggcgtagc tttccccggg caggtattgc tcgcagaccc tgcgtggggc tgtggagggg 31560 acggcctcca tgaagcgaca tttactctgc tcgcgtttac tgacgtcacc atccatcgcc 31620 acggcgattg gacgattgtt aagccgcagc gtgtctccgc ttgtgctgta gtagtcaaaa 31680 acgtaatggc cgtcggagtc ggcaaagcgg gccgggaggt cgtcgccgag cgggacgacc 31740 cgccgccccc gaccgccccg tccccccagg tgtgccagga cggccagggc atacgcggtg 31800 tgaaaaaagg cgtcgggggc ggtcccctcg acggcgcgca tcaggttctc gaggagaatg 31860 gggaagcgcc tggtcacctc ccccagccac gcgcgttggt cggggccaaa gtcatagcgc 31920 aggcgctgtg agattcgagg gccgccctga agcgcggccc ggatggcctg gcccagggcc 31980 cggaggcacg ccagatgtat gcgcgcagta aaggcgacct cggcggcgat gtcaaagggc 32040 ggcaggacgg ggcgcgggtg gcgcaggggc acctcgagcg cgggaaagcg gagcagcagc 32100 tccgcctgcc cagcgggaga cagctggtgg gggcgcacga cgcgttctgc ggcgcaggcc 32160 tcggtcaggg ccgtggccag cgccgaggac agcagcggag ggcgggcgcg tcgcccgccc 32220 cacgccacgg agttctcgta ggagacgacg acgaagcgct gcttggttcc gtagtggtgg 32280 cgcaggacca cggagataga acgacggctc cacagccagt ccggccggtc gccgccggcc 32340 agggcttccc atccgcgatc caaccactcg accagcgacc gcggctttgc ggtaccaggg 32400 gtcagggtta gaacgtcgtt caggatgtcc tcgcccccgg gcccgtgggg cactggggcc 32460 acaaagcggc ccccgcctgg gggctccaga cccgccaaca ccgcatctgc gtcagccgcc 32520 cccatggcgc ccccgctgac ggcctggtga accagggcgc cctggcggag ccccgatgca 32580 acgccacagg ccgcacgccc ggtccgagcg cggaccgggt ggcggcgggt gacgtcctgc 32640 actgcccgct gaaccaacgc gaggatctcc tcgttctcct gcgcgatgga cacgtcctgg 32700 gccgcggtcg tgtcgccgcc gggggccgtc agctgctcct ccggggagat gggggggtcg 32760 gacgccccga cgatgggcgg gtctgcgggc gcccccgcgt ggggccgggc caagggctgc 32820 ggacgcgggg acgcgctttc ccccagaccc atggacaggt gggccgcagc ctccttcgcg 32880 gccggcgggg cggcggcgcc aagcagagcg acgtagcggc acaaatgccg acagacgcgc 32940 atgatgcgcg tgctgtcggc cgcgtagcgc gtgttggggg ggacgagctc gtcgtaacta 33000 aacagaatca cgcgggcaca gctcgccccc gagccccacg caaggcgcag cgccgccacg 33060 gcgtacgggt catagacgcc ctgtgcgtca cacaccacgg gcaaggagac gaacaacccc 33120 ccggcgctgg acgcacgcgg aaggaggcca gggtgtgccg gcacgacggg ggccagaagc 33180 tcccccaccg catccgcggg cacgtaggcg gcaaacgccg tgcaccacgg ggtacagtcg 33240 ccggtggcat gagcccgagt ctggatttcg acctggaagt ttgcggccgt cccgagtccg 33300 gggcggccgc gcatcagggc ggccagaggg attcccgcgg ccgccaggca ctcgctggat 33360 atgatgacgt gaaccaaaga cgagggccga cccgggacgt ggccgagatc gtactggacc 33420 tcgttggcca agtgcgcgtt catggttcgg gggtgggtgt gggtgtgtag gcgatgcggg 33480 tcccccgagt ccgcgggaag ggcgcgggtt tggcgcgcgt atgcgtattc gccaacggag 33540 gcgtgcgtgc ttatgcgcgg cgcgtttctt ctgtctccag ggaatccgag gccaggactt 33600 taacctgctc tttgtcgacg aggccaactt tattcgcccg gatgcggtcc agacgattat 33660 gggctttctc aaccaggcca actgcaagat tatcttcgtg tcgtccacca acaccgggaa 33720 ggccagtacg agctttttgt acaacctccg cggggccgcc gacgagcttc tcaacgtggt 33780 gacctatata tgcgatgatc acatgccgcg ggtggtgacg cacacaaacg ccacggcctg 33840 ttcttgttat atcctcaaca agcccgtttt catcacgatg gacggggcgg ttcgccggac 33900 cgccgatttg tttctggccg attccttcat gcaggagatc atcgggggcc aggccaggga 33960 gaccggcgac gaccggcccg ttctgaccaa gtctgcgggg gagcggtttc tgttgtaccg 34020 cccctcgacc accaccaaca gcggcctcat ggcccccgat ttgtacgtgt acgtggatcc 34080 cgcgttcacg gccaacaccc gagcctccgg gaccggcgtc gctgtcgtcg ggcggtaccg 34140 cgacgattat atcatcttcg ccctggagca cttttttctc cgcgcgctca cgggctcggc 34200 ccccgccgac atcgcccgct gcgtcgtcca cagtctgacg caggtcctgg ccctgcatcc 34260 cggggcgttt cgcggcgtcc gggtggcggt cgagggaaat agcagccagg actcggccgt 34320 cgccatcgcc acgcacgtgc acacagagat gcaccgccta ctggcctcgg agggggccga 34380 cgcgggctcg ggccccgagc ttctcttcta ccactgcgag cctcccggga gcgcggtgct 34440 gtaccccttt ttcctgctca acaaacagaa gacgcccgcc tttgaacact ttattaaaaa 34500 gtttaactcc gggggcgtca tggcctccca ggagatcgtt tccgcgacgg tgcgcctgca 34560 gaccgacccg gtcgagtatc tgctcgagca gctgaataac ctcaccgaaa ccgtctcccc 34620 caacacggac gtccgtacgt attccggaaa acggaacggc gcctcggatg accttatggt 34680 cgccgtcatt atggccatct accttgcggc ccaggccgga cctccgcaca cattcgctcc 34740 catcacacgc gtttcgtgag cgcccaataa acacacccag gtatgctacg cacgaccacg 34800 gtgtcgcctg ttaagggggg gggaaggggg tgttggcggg aagcgtggga acacggggga 34860 ttctctcacg accggcacca gtaccacccc cctgtgaaca cagaaacccc aacccaaatc 34920 ccataaacat acgacacaca ggcatatttt ggaatttctt aggtttttat ttatttaggt 34980 atgctggggt ttctccctgg atgcccaccc ccaccccccc ccgtgggtct agccgggcct 35040 tagggatagc gtataacggg ggccatgtct ccggaccgca caacggccgc gccgtcaaag 35100 gtgcacaccc gaaccacggg agccagggcc aaggtgtctc ctagttggcc cgcgtgggtc 35160 agccaggcga cgagcgcctc gtagagcggc agccttcgct ctccatcctg catcagggcc 35220 ggggcttcgg ggtgaatgag ctgggcggcc tcccgcgtga cactctgcat ctgcaggaga 35280 gcgttcacgt acccgtcctg ggcacttagc gcaaagagcc gggggattag cgtaaggatg 35340 atggtggttc cctccgtgat cgagtaaacc atgttaagga ccagcgatcg cagctcggcg 35400 tttacggggc cgagttgttg gacgtccgcc agcagcgaga ggcgactccc gttgtagtac 35460 agcacgttga ggtctggcag ccctccgggg tttctggggc tggggttcag gtcccggatg 35520 cccctggcca cgagccgcgc cacgatttcg cgcgccaggg gcgatggaag cggaacggga 35580 aaccgcaacg tgaggtccag cgaatccagg cgcacgtccg tcgcttggcc ctcgaacacg 35640 ggcgggacga ggctgatggg gtccccgtta cagagatcta cgggggaggt gttgcgaagg 35700 ttaacggtgc cggcgtgggt gaggcccacg tccagggggc aggcgacgat tcgcgtggga 35760 agcacccggg tgatgaccgc ggggaagcgc cttcggtacg ccagcaacag ccccaacgtg 35820 tcgggactga cgcctccgga gacgaaggat tcgtgcgcca cgtcggccag cgtcagttgc 35880 cggcggatgg tcggcaggaa taccacccgc ccttcgcagc gctgcagcgc cgccgcatcg 35940 gggcgcgaga tgcccgaggg tatcgcgatg tcagtttcaa agccgtccgc cagcatggcg 36000 ccgatccacg cggcagggag tgcagtggtg gttcgggtgg cgggaggagc gcggtggggg 36060 tcagcggcgt agcagagacg ggcgaccaac ctcgcatagg acggggggtg ggtcttaggg 36120 ggttgggagg cgacagggac cccagagcat gcgcggggag gtctgtcggg cccagacgca 36180 ccgagagcga atccgtccat ggagtcccgg cctgggtttt atggggcccg gccctcggaa 36240 tcgcggcttg tcggcgggga caaagggggc ggggctaggg ggcttgcgga aacagaagac 36300 gtgtgggata aaagaatcgc actaccccaa ggaagggcgg ggcggtttat tacagagcca 36360 gtcccttgag cggggatgcg tcatagacga gatactgcgc gaagtgggtc tcccgcgcgt 36420 gggcttcccc gttgcgggcg ctgcggagga gggcggggtc gctggcgcag gtgagcgggt 36480 aggcctcctg aaacaggcca cacgggtcct ccacgagttc gcggcacccc ggggggcgct 36540 taaactgtac gtcgctggcg gcggtggccg tggacaccgc cgaacccgtc tccacgatca 36600 ggcgctccag gcagcgatgt ttggcggcga tgtcggccga cgtaaagaac ttaaagcagg 36660 ggctgagcac cggcgaggcc ccgttgaggt ggtaggcccc gttatagagc aggtccccgt 36720 acgaaaatcg ctgcgacgcc cacgggttgg ccgtggccgc gaaggcccgg gacgggtcgc 36780 tctggccgtg gtcgtacatg agggcggtga catccccctc cttgtccccc gcgtaaacgc 36840 ccccggcggc gcgtccccgg gggttgcagg gccggcggaa gtagttgacg tcggtcgaca 36900 cgggggtggc gataaactca cacacggcgt cctggccgtg gtccatccct gcgcgccgcg 36960 gcacctgggc gcacccgaac acggggacgg gctgggccgg ccccaggcgg tttcccgcca 37020 cgaccgcgtt ccgcaggtac acggctgccg cgttgtccag tagaggggga gccccgcggc 37080 ccaggtaaaa gttttgggga aggttgccca tgtcggtgac ggggttgcgg acggttgccg 37140 tggccacgac ggcggtgtag cccacgccca ggtccacgtt cccgcgcggc tgggtgagcg 37200 tgaagtttac ccccccgcca gtttcatgcc gggccacctg gagctggccc aggaagtacg 37260 cctccgacgc gcgctccgag aacagcacgt tctcagtcac aaagcggtcc tgtcggacga 37320 cggtgaaccc aaacccggga tggaggcccg tcttgagctg atgatgcaag gccacgggac 37380 tgatcttgaa gtaccccgcc atgagcgcgt aggtcagcgc gttctccccg gccgcgctct 37440 cgcggacgtg ctgcacgacg ggctgtcgga tcgacgaaaa gtagttggcc cccagagccg 37500 gggggaccag ggggacctgc cgcgacaggt cgcgcagggc cggggggaaa ttgggcgcgt 37560 tcgccacgtg gtcggccccg gcgaacagcg cgtggacggg gagggggtaa aaatagtcgc 37620 cattttggat ggtatggtcc agatgctggg gggccatcag caggattccg gcgtgcaacg 37680 ccccgtcgaa tatgcgcatg ttggtggtgg acgcggtgtt ggcgcccgcg tcgggcgccg 37740 ccgagcagag cagcgccgtt gtgcgttcgg ccatgttgtg ggccagcacc tgcagcgtga 37800 gcatggcggg cccgtccact accacgcgcc cgttgtgaaa catggcgttg accgtgttgg 37860 ccaccagatt ggccgggtgc agggggtgcg cggggtccgt cacggggtcg ctggggcaat 37920 cctcgccggg ggtgatctcc gggaccacca tgttctgcag ggtggcgtat acgcggtcga 37980 agcgaacccc cgcggtgcag cagcggcccc gcgagaaggc gggcaccatc acgtagtagt 38040 aaatcttgtg gtgcacggtc cagtccgccc cccggtgcgg ccggtcgtcc gcggcgtccg 38100 cggctcgggc ctgggtgttg tgcagcagct ggccgtcgtt gcggttgaag tccgcggtcg 38160 ccacgttaca cgccgctgcg tacacggggt cgtggccccc cgcgctaacc cggcagtcgc 38220 gatggcggtc cagggccgcg cgccgcatca gggcgtcgca gtcccacacg aggggtggca 38280 gcagcgccgg gtctcgcatt aggtgattca gttcggcttg cgcctgcccg cccagttccg 38340 ggccggtcag ggtaaagtca tcaaccagct gggccagggc ctcgacgtgc gccaccaggt 38400 cccggtacac ggccatgcac tcctcgggaa ggtctccccc gaggtaggtc acgacgtacg 38460 agaccagcga gtagtcgttc acgaacgccg cgcaccgcgt gttgttccag tagctggtga 38520 tgcactggac cacgagccgg gccagggcgc agaagacgtg ctcgctgccg tgtatggcgg 38580 cctgcagcag gtaaaacacc gccgggtagt tgcggtcttc gaacgccccg cgaacggcgg 38640 cgatggtggc gggggccatg gcgtggcgtc ccacccccag ctccaggccc cgggcgtccc 38700 ggaacgccgc cggacatagc gccaggggca agttgccgtt caccacgcgc caggtggcct 38760 ggatctcccc cgggccggcc gggggaacgt ccccccccgg cagctccacg tcggccaccc 38820 ccacgaagaa gtcgaacgcg gggtgcagct caagagccag gttggcgttg tcgggctgca 38880 taaactgctc cggggtcatc tggccttccg cgacccatcg gacccgcccg tgggccaggc 38940 gctgccccca ggcgttcaaa aacagctgct gcatgtctgc ggcggggccg gccggggccg 39000 ccacgtacgc cccgtacgga ttggcggctt cgacggggtc gcggttaagg cccccgaccg 39060 ccgcgtcaac gttcatcagc gaagggtggc acacggtccc gatcgcgtgt tccagagaca 39120 ggcgcagcac ctggcggtcc ttcccccaaa aaaacagctg gcggggcggg aaggcgcggg 39180 gatccgggtg gccgggggcg gggactaggt ccccggcgtg cgcggcaaac cgttccatga 39240 ccggattgaa caggcccagg ggcaggacga acgtcaggtc catggcgccc accagggggt 39300 agggaacgtt ggtggcggcg tagatgcgct tctccagggc ctccaaaaag atcagcttct 39360 cgccgatgga caccagatcc gcgcgcacgc gcgtcgtctg gggggcgctc tcgagctcgt 39420 ccagcgtctg ccggttcagg tcgagctgct cctcctgcat ctccagcagg tggcggccca 39480 cgtcgtccag acttcgcacg gccttgccca tcacgagcgc cgtgaccagg ttggccccgt 39540 tcaggaccat ctcgccgtac gtcaccggca cgtcggcttc ggtgtcctcc actttcagga 39600 aggactgcag gaggcgctgt ttgatcgggg cggtggtgac gagcaccccg tcgaccggac 39660 gcccgcgcgt gtcggcatgc gtcagacggg gcacggccac ggagggctgc gtggccgtgg 39720 tgaggtccac gagccaggcc tcgacggcct cccggcggtg gcccgccttg cccaggaaaa 39780 agctcgtctc gcagaagctt cgctttagct cggcgaccag ggtcgcccgg gccaccctgg 39840 tggccaggcg gccgttgtcc aggtatcgtt gcatcggcaa caacaaagcc aggggcggcg 39900 ccttttccag cagcacgtgc agcatctggt cggccgtgcc gcgctcaaac gccccgagga 39960 cggcctggac gttgcgagcg agctgttgga tggcgcgcaa ctggcgatgc gcgctgatac 40020 ccgtcccgtc cagggcctcc cccgtgagca gggcgatggc ctcggtggcc aggctgaagg 40080 cggcgttcag ggcccggcgg tcgataatct tggtcatgta attgtgtgtg ggttgctcga 40140 tggggtgcgg gccgtcgcgg gcaatcagcg gctggtggac ctcgaactgt acgcgcccct 40200 cgttcatgta ggccagctcc ggaaacttgg tacacacgca cgccaccgac aacccgagct 40260 ccagaaagcg cacgagcgac agggtgttgc aatacgaccc caacagggcg tcgaactcga 40320 cgtcatacag gctgtttgca tcggagcgca cgcgggaaaa aaaatcgaac aggcgtcgat 40380 gcgacgccac ctcgatcgtg ctaaggaggg acccggtcgg caccatggcc gcggcatacc 40440 ggtatcccgg agggtcgcgg ttgggagcgg ccatggggtc gcgtggagat cggctgtctc 40500 tagcgatatt ggcccgggga ggctaagatc caccccaacg cccggccacc cgtgtacgtg 40560 cccgacggcc caaggtccac cgaaagacac gacgggcccg gacccaaaaa ggcgggggat 40620 gctgtgtgag aggccgggtg tcggtcgggg gggaaaggca ccgggagaag gctgcggcct 40680 cgttccagga gaacccagtg tccccaacag acccggggac gtgggatccc aggccttata 40740 tacccccccc gccccacccc cgttagaacg cgacgggtgc attcaagatg gccctggtcc 40800 aaaagcgtgc caggaagaaa ttggcagagg cggcaaagct gtccgccgcc gccacccaca 40860 tcgaggcccc ggccgcgcag gctatcccca gggcccgtgt gcgcagggga tcggtgggcg 40920 gcagcatttg gttggtggcg ataaagtgga aaagcccgtc cggactgaag gtctcgtggg 40980 cggcggcgaa caaggcacac agggccgtgc ctcccaaaaa cacggacatc ccccaaaaca 41040 cgggcgccga caacggcaga cgatccctct tgatgttaac gtacaggagg agcgcccgca 41100 ccgcccacgt aacgtagtag ccgacgatgg cggccaggat acaggccggc gccaccaccc 41160 ttccggtcag cccgtaatac atgcccgctg ccaccatctc caacggcttc aggaccaaaa 41220 acgaccaaag gaacagaatc acgcgctttg aaaagaccgg ctgggtatgg ggcggaagac 41280 gcgagtatgc cgaactgaca aaaaagtcag aggtgccgta cgaggacaat gaaaactgtt 41340 cctccagtgg cagttctccc tcctcccccc caaaggcggc ctcgtcgacc agatctcgat 41400 ccaccagagg aaggtcatcc cgcatggtca tggggtgtgc ggtggaggtg gggagaccga 41460 aaccgcaaag ggtcgcttac gtcagcagga tcccgagatc aaagacaccc gggttcttgc 41520 acaaacacca cccgggttgc atccgcggag gcgagtgttt tgataaggcc gttccgcgcc 41580 ttgatataac ctttgatgtt gaccacaaaa cccggaattt acgcctacgc cccaatgccc 41640 acgcaagatg aggtaggtaa cccccccccc gtgggtgtga cgttgcgttt agttcattgg 41700 aggccaaggg gaaaatgggg tggggaggaa acggaaaacc cagtaggccg tgttgggaac 41760 acgcccgggg ttgtcctcaa aaggcagggt ccatactacg gaagccgtcg ttgtattcga 41820 gacctgcctg tgcgacgcac gtcggggttg cctgtgtccg gttcggcccc accgcgtgcg 41880 gcacgcacga ggacgagtcc gcgtgcttta ttggcgttcc aagcgttgcc ctccagtttc 41940 tgttgtcggt gttcccccat acccacgccc acatccaccg tagggggcct ctgggccgtg 42000 tcacgtcgcc gcccgcgatg gagcttagct acgccaccac catgcactac cgggacgttg 42060 tgttttacgt cacaacggac cgaaaccggg cctactttgt gtgcgggggg tgtgtttatt 42120 ccgtggggcg gccgtgtgcc tcgcagcccg gggagattgc caagtttggt ctggtcgttc 42180 gagggacagg cccagacgac cgcgtggtcg ccaactatgt acgaagcgag ctccgacaac 42240 gcggcctgca ggacgtgcgt cccattgggg aggacgaggt gtttctggac agcgtgtgtc 42300 ttctaaaccc gaacgtgagc tccgagctgg atgtgattaa cacgaacgac gtggaagtgc 42360 tggacgaatg tctggccgag tactgcacct cgctgcgaac cagcccgggt gtgctaatat 42420 ccgggctgcg cgtgcgggcg caggacagaa tcatcgagtt gtttgaacac ccaacgatag 42480 tcaacgtttc ctcgcacttt gtgtataccc cgtccccata cgtgttcgcc ctggcccagg 42540 cgcacctccc ccggctcccg agctcgctgg aggccctggt gagcggcctg tttgacggca 42600 tccccgcccc acgccagcca cttgacgccc acaacccgcg cacggatgtg gttatcacgg 42660 gccgccgcgc cccacgaccc atcgccgggt cgggggcggg gtcggggggc gcgggcgcca 42720 agcgggccac cgtcagcgag ttcgtgcaag tcaaacacat tgaccgcgtg ggccccgctg 42780 gcgtttcgcc ggcgcctccg ccaaacaaca ccgactcaag ttccctggtg cccggggccc 42840 aggattccgc cccgcccggc cccacgctaa gggagctgtg gtgggtgttt tatgccgcag 42900 accgggcgct ggaggagccc cgcgccgact ctggcctcac ccgcgaggag gtacgtgccg 42960 tacgtgggtt ccgggagcag gcgtggaaac tgtttggctc cgcgggggcc ccgcgggcgt 43020 ttatcggggc cgcgttgggc ctgagccccc tccaaaagct agccgtttac tactatatca 43080 tccaccgaga gaggcgcctg tcccccttcc ccgcgctagt ccggctcgta ggccggtaca 43140 cacagcgcca cggcctgtac gtccctcggc ccgacgaccc agtcttggcc gatgccatca 43200 acgggctgtt tcgcgacgcg ctggcggccg gaaccacagc cgagcagctc ctcatgttcg 43260 accttctccc cccaaaggac gtgccggtgg gaagcgacgt gcaggccgac agcaccgctc 43320 tgctgcgctt tatagaatcg caacgtctcg ccgtccccgg gggggtgatc tcccccgagc 43380 acgtcgcgta ccttggtgcg ttcctgagcg tgctgtacgc tggccgcggg cgcatgtccg 43440 cagccacgca caccgcgcgg ctgacagggg tgacctccct ggtgctagcg gtgggtgacg 43500 tggaccgtct ttccgcgttt gaccgcggag cggcgggcgc ggccagccgc acgcgggccg 43560 ccgggtacct ggatgtgctt cttaccgttc gtctcgctcg ctcccaacac ggacagtctg 43620 tgtaacagac cccaataaac gtatgtcgct accacaccct tgtgtgtcaa tggacgcctc 43680 tccggggggg aagggaaaac aaagaggggc tgggggagcg gcaccaccgg ggcctgaaca 43740 aacaaaccac agacacggtt acagtttatt cggtcgggcg gagaaacggc cgaagccacg 43800 ccccctttat tcgcgtctcc aaaaaaacgg gacacttgtc cggagaacct ttaggatgcc 43860 agccagggcg gcggtaatca taaccacgcc cagcgcagag gcggccagaa acccgggcgc 43920 aattgcggcc acgggctgcg tgtcaaaggc tagcaaatga atgacggttc cgtttggaaa 43980 tagcaacaag gccgtggacg gcacgtcgct cgaaaacacg cttggggcgc cctccgtcgg 44040 cccggcggcg atttgctgct gtgtgttgtc cgtatccacc agcaacacag acatgacctc 44100 cccggccggg gtgtagcgca taaacacggc ccccacgagc cccaggtcgc gctggttttg 44160 ggtgcgcacc agccgcttgg actcgatatc ccgggtggag ccttcgcatg tcgcggtgag 44220 gtaggttagg aacagtgggc gtcggacgtc gacgccggtg agcttgtagc cgatcccccg 44280 gggcagaggg gagtgggtga cgacgtagct ggcgttgtgg gtgatgggta ccaggatccg 44340 tggctcgacg ttggcagact gccccccgca ccgatgtgag gcctcaggga cgaaggcgcg 44400 gatcagggcg ttgtagtgtg cccagcgcgt cagggtcgag gcgaggccgt gggtctgctg 44460 ggccaggact tcgaccgggg tctcggatcg ggtggcttga gccagcgcgt ccaggataaa 44520 cacgctctcg tctagatcaa agcgcaggga ggccgcgcat ggcgaaaagt ggtccggaag 44580 ccaaaagagg gttttctggt ggtcggcccg ggccagcgcg gtccggaggt cggcgttggt 44640 cgctgcggcg acgtcggacg tacacagggc cgaggctatc agaaggctcc ggcgggcgcg 44700 ttcccgctgc accgccgagg ggacgcccgc caagaacggc tgccggagga cagccgaggc 44760 gtaaaatagc gcccggtgga cgaccggggt ggtcagcacg cggcccccta gaaactcggc 44820 atacagggcg tcgatgagat gggctgcgct gggcgccact gcgtcgtacg ccgaggggct 44880 atccagcacg aaggccagct gatagcccag cgcgtgtaat gccaagctct gttcgcgctc 44940 cagaatctcg gccaccaggt gctggagccg agcctctagc tgcaggcggg ccgtgggatc 45000 caagactgac acattaaaaa acacagaatc cgcggcacag cccgcggccc cgcgggcggc 45060 caacccggca agcgcgcgcg agtgggccaa aaagcctagc aggtcggaga ggcagaccgc 45120 gccgtttgcg tgggcggcgt tcacgaaagc aaaacccgac gtcgcgagca gccccgttag 45180 gcgccagaag agagggggac gcgggccctg ctcggcgccc gcgtcccccg agaaaaactc 45240 cgcgtatgcc cgcgacagga actgggcgta gttcgtgccc tcctccgggt agccgcccac 45300 gcggcggagg gcgtccagcg cggagccgtt gtcggcccgc gtcagggacc ctaggacaaa 45360 gacccgatac cgggggccgc ccgggggccc gggaagagcc cccggggggt tttcgtccgc 45420 ggggtccccg acccgatcta gcgtctggcc cgcggggacc accatcactt ccaccggagg 45480 gctgtcgtgc atggatatca cgagccccat gaattcccgc ccgtagcgcg cgcgcaccag 45540 cgcggcatcg cacccgagca ccagctcccc cgtcgtccag atgcccacgg gccacgtcga 45600 ggccgacggg gagaaataca cgtacctacc tggggatctc aacaggcccc gggtggccaa 45660 ccaggtcgtg gacgcgttgt gcaggtgcgt gatgtccagc tccgtcgtcg ggtgccgccg 45720 ggccccaacc ggcggtcggg ggggcggtgt atcacgcggc ccgctcgggt ggctcgccgt 45780 cgccacgttg tctccccgcg ggaacgtcag ggcctcgggg tcagggacgg ccgaaaacgt 45840 tacccaggcc cgggaacgca gcaacacgga ggcggttgga ttgtgcaaga gacccttaag 45900 gggggcgacc gcggggggag gctgggcggt cggctcgacc gtgatggggg cgggcaggct 45960 cgcgttcggg ggccggccga gcaggtaggt cttcgagatg taaagcagct ggccggggtc 46020 ccgcggaaac tcggccgtgg tgaccaatac aaaacaaaag cgctcctcgt accagcgaag 46080 aaggggcaga gatgccgtag tcaggtttag ttcgtccggc ggcgccagaa atccgcgcgg 46140 tggtttttgg gggtcggggg tgtttggcag ccacagacgc ccggtgttcg tgtcgcgcca 46200 gtacatgcgg tccatgccca ggccatccaa aaaccatggg tctgtctgct cagtccagtc 46260 gtggacctga ccccacgcaa cgcccaaaag aataaccccc acgaaccata aaccattccc 46320 catgggggac cccgtcccta acccacgggg cccgtggcta tggcagggct tgccgccccg 46380 acgttggctg cgagccctgg gccttcaccc gaacttgggg gttggggtgg ggaaaaggaa 46440 gaaacgcggg cgtattggcc ccaatggggt ctcggtgggg tatcgacaga gtgccagccc 46500 tgggaccgaa ccccgcgttt atgaacaaac gacccaacac ccgtgcgttt tattctgtct 46560 ttttatttcc gtcatagcgc gggttccttc cggtattgtc tccttccgtg tttcagttag 46620 cctcccccat ctcccgggca aacgtgcgcg ccaggtcgca gatcgtcggt atggagcctg 46680 gggtggtgac gtgggtctgg accatcccgg aggtaagttg cagcagggcg tcccggcagc 46740 cggcgggcga ttggtcgtaa tccaggataa agacgtgcat gggacggagg cgtttggcca 46800 agacgtccaa ggcccaggca aacacgttat acaggtcgcc gttgggggcc agcaactcgg 46860 gggcccgaaa cagggtaaat aacgtgtccc cgatatgggg tcgtgggccc gcgttgctct 46920 ggggctcggc accctggggc ggcacggccg tccccgaaag ctgtccccaa tcctcccgcc 46980 acgacccgcc gccctgcaga taccgcaccg tattggcaag cagcccgtaa acgcggcgaa 47040 tcgcggccaa catagccagg tcaagccgct cgccggggcg ctggcgtttg gccaggcggt 47100 cgatgtgtct gtcctccgga agggccccca acacgatgtt tgtgccgggc aaggtcggcg 47160 ggatgagggc cacgaacgcc agcacggcct ggggggtcat gctgcccata aggtatcgcg 47220 cggccgggta gcacaggagg gcggcgatgg gatggcggtc gaagatgagg gtgagggccg 47280 ggggcggggc atgtgagctc ccagcctccc ccccgatatg aggagccaga acggcgtcgg 47340 tcacggcata aggcatgccc attgttatct gggcgcttgt cattaccacc gccgcgtccc 47400 cggccgatat ctcaccctgg tcgaggcggt gttgtgtggt gtagatgttc gcgattgtct 47460 cggaagcccc cagcacctgc cagtaagtca tcggctcggg tacgtagacg atatcgtcgc 47520 gcgaacccag ggccaccagc agttgcgtgg tggtggtttt ccccatcccg tgaggaccgt 47580 ctatataaac ccgcagtagc gtgggcattt tctgctccag gcggacttcc gtggcttctt 47640 gctgccggcg agggcgcaac gccgtacgtc ggttgctatg gccgcgagaa cgcgcagcct 47700 ggtcgaacgc agacgcgtgt tgatggcagg ggtacgaagc catacgcgct tctacaaggc 47760 gcttgccaaa gaggtgcggg agtttcacgc caccaagatc tgcggcacgc tgttgacgct 47820 gttaagcggg tcgctgcagg gtcgctcggt gttcgaggcc acacgcgtca ccttaatatg 47880 cgaagtggac ctgggaccgc gccgccccga ctgcatctgc gtgttcgaat tcgccaatga 47940 caagacgctg ggcggggttt gtgtcatcat agaactaaag acatgcaaat atatttcttc 48000 cggggacacc gccagcaaac gcgagcaacg ggccacgggg atgaagcagc tgcgccactc 48060 cctgaagctc ctgcagtccc tcgcgcctcc gggtgacaag atagtgtacc tgtgccccgt 48120 cctggtgttt gtcgcccaac ggacgctccg cgtcagccgc gtgacccggc tcgtcccgca 48180 gaaggtctcc ggtaatatca ccgcagtcgt gcggatgctc cagagcctgt ccacgtatac 48240 ggtccccatg gagcctagga cccagcgagc ccgtcgccgc cgcggcggcg ctgcccgggg 48300 gtctgcgagc agaccgaaaa ggtcacactc tggggcgcgc gacccgcccg agccagcggc 48360 ccgccaggta ccacccgccg accaaacccc cgcctccacg gagggcgggg gggtgcttaa 48420 gaggatcgcg gcgctcttct gcgtgcccgt ggccaccaag accaaacccc gagctgcctc 48480 cgaatgagag tgtttcgttc cttccccctc cccccgcgtc agacaaaccc taaccaccgc 48540 ttaagcggcc cccgcgaggt ccgaagactc atttggatcc ggcgggagcc acctgacaac 48600 agcccccggg tttccccacg ccagacgccg gtccgctgtg ccatcgctcc ccttcatccc 48660 acccccatct tgtccccaaa taaaacaagg tctggtagtt aggacaacga ccgcagttct 48720 cgtgtgttat tgtcgctctc cgcctctcgc agatggaccc gtattgccca tttgacgctc 48780 tggacgtctg ggaacacagg cgcttcatag tcgccgattc ccgaaacttc atcacccccg 48840 agttcccccg ggacttttgg atgtcgcccg tctttaacct cccccgggag acggcggcgg 48900 agcaggtggt cgtcctgcag gcccagcgca cagcggctgc cgctgccctg gagaacgccg 48960 ccatgcaggc ggccgagctc cccgtcgata tcgagcgccg gttacgcccg atcgaacgga 49020 acgtgcacga gatcgcaggc gccctggagg cgctggagac ggcggcggcc gccgccgaag 49080 aggcggatgc cgcgcgcggg gatgagccgg cgggtggggg cgacgggggg gcgcccccgg 49140 gtctggccgt cgcggagatg gaggtccaga tcgtgcgcaa cgacccgccg ctacgatacg 49200 acaccaacct ccccgtggat ctgctacata tggtgtacgc gggccgcggg gcgaccggct 49260 cgtcgggggt ggtgttcggg acctggtacc gcactatcca ggaccgcacc atcacggact 49320 ttcccctgac cacccgcagt gccgactttc gggacggccg gatgtccaag accttcatga 49380 cggcgctggt cctgtccctg cagtcgtgcg gccggctgta tgtgggccag cgccactatt 49440 ccgccttcga gtgcgccgtg ttgtgtctct acctgctgta ccgaaacacg cacggggccg 49500 ccgacgatag cgaccgcgct ccggtcacgt tcggggatct gctgggccgg ctgccccgct 49560 acctggcgtg cctggccgcg gtgatcggga ccgagggcgg ccggccacag taccgctacc 49620 gcgacgacaa gctccccaag acgcagttcg cggccggcgg gggccgctac gaacacggag 49680 cgctggcgtc gcacatcgtg atcgccacgc tgatgcacca cggggtgctc ccggcggccc 49740 cgggggacgt cccccgggac gcgagcaccc acgttaaccc cgacggcgtg gcgcaccacg 49800 acgacataaa ccgcgccgcc gccgcgttcc tcagccgggg ccacaaccta ttcctgtggg 49860 aggaccagac tctgctgcgg gcaaccgcga acaccataac ggccctgggc gttatccagc 49920 ggctcctcgc gaacggcaac gtgtacgcgg accgcctcaa caaccgcctg cagctgggca 49980 tgctgatccc cggagccgtc ccttcggagg ccatcgcccg tggggcctcc gggtccgact 50040 cgggggccat caagagcgga gacaacaatc tggaggcgct atgtgccaat tacgtgcttc 50100 cgctgtaccg ggccgacccg gcggtcgagc tgacccagct gtttcccggc ctggccgccc 50160 tgtgtcttga cgcccaggcg gggcggccgg tcgggtcgac gcggcgggtg gtggatatgt 50220 catcgggggc ccgccaggcg gcgctggtgc gcctcaccgc cctggaactc atcaaccgca 50280 cccgcacaaa ccccaccccc gtgggggagg ttatccacgc ccacgacgcc ctggcgatcc 50340 aatacgaaca ggggcttggc ctgctggcgc agcaggcacg cattggcttg ggctccaaca 50400 ccaagcgttt ctccgcgttc aacgttagca gcgactacga catgttgtac tttttatgtc 50460 tggggttcat tccacagtac ctgtcggcgg tttagtgggt ggtgggcgag gggggagggg 50520 gcattaggga gaaagaacaa gagcctccgt tgggttttct ttgtgcctgt actcaaaagg 50580 tcataccccg taaacggcgg gctccagtcc cggcccggcg gttggcgtga acgcaacggc 50640 gggagctggg ttagcgttta gtttagcatt cgctctcgcc tttccgcccg cccccgaccg 50700 ttgagccttt ttttttttcg tccaccaaag tctctgtggg tgcgcgcatg gcagccgatg 50760 ccccgggaga ccggatggag gagcccctgc cagacagggc cgtgcccatt tacgtggctg 50820 ggtttttggc cctgtatgac agcggggact cgggcgagtt ggcattggat ccggatacgg 50880 tgcgggcggc cctgcctccg gataacccac tcccgattaa cgtggaccac cgcgctggct 50940 gcgaggtggg gcgggtgctg gccgtggtcg acgacccccg cgggccgttt tttgtgggac 51000 tgatcgcctg cgtgcaactg gagcgcgtcc tcgagacggc cgccagcgct gcgattttcg 51060 agcgccgcgg gccgccgctc tcccgggagg agcgcctgtt gtacctgatc accaactacc 51120 tgccctcggt ctccctggcc acaaaacgcc tggggggcga ggcgcacccc gatcgcacgc 51180 tgttcgcgca cgtagcgctg tgcgcgatcg ggcggcgcct tggcactatc gtcacctacg 51240 acaccggtct cgacgccgcc atcgcgccct ttcgccacct gtcgccggcg tctcgcgagg 51300 gggcgcggcg actggccgcc gaggccgagc tcgcgctatc cggacgcacc tgggcgcccg 51360 gcgtggaggc gctgacccac acgctgcttt ccaccgccgt taacaacatg atgctgcggg 51420 accgctggag cctggtggcc gagcggcggc ggcaggccgg gatcgccgga cacacctacc 51480 tccaggcgag cgaaaaattc aaaatgtggg gggcggagcc tgtttccgcg ccggcgcgcg 51540 ggtataagaa cggggccccg gagtccacgg acataccgcc cggctcgatc gctgccgcgc 51600 cgcagggtga ccggtgccca atcgtccgtc agcgcggggt cgcctcgccc ccggtactgc 51660 cccccatgaa ccccgttcca acatcgggca ccccggcccc cgcgccgccc ggcgacggga 51720 gctacctgtg gatcccggcc tcccattaca accagctcgt cgccggccac gccgcgcccc 51780 aaccccagcc gcattccgcg tttggtttcc cggctgcggc gggggccgtg gcctatgggc 51840 ctcacggcgc gggtctttcc cagcattacc ctccccacgt cgcccatcag tatcccgggg 51900 tgctgttctc gggacccagc ccactcgagg cgcagatagc cgcgttggtg ggggccatag 51960 ccgcggaccg ccaggcgggc ggtcagccgg ccgcgggaga ccctggggtc cgggggtcgg 52020 gaaagcgtcg ccggtacgag gcggggccgt cggagtccta ctgcgaccag gacgaaccgg 52080 acgcggacta cccgtactac cccggggagg ctcgaggcgg gccgcgcggg gtcgactctc 52140 ggcgcgcggc ccgccagtct cccgggacca acgagaccat cacggcgctg atgggggcgg 52200 tgacgtctct gcagcaggaa ctggcgcaca tgcgggctcg gaccagcgcc ccctatggaa 52260 tgtacacgcc ggtggcgcac tatcgccctc aggtggggga gccggaacca acaacgaccc 52320 acccggccct ttgtcccccg gaggccgtgt atcgcccccc accacacagc gccccctacg 52380 gtcctcccca gggtccggcg tcccatgccc ccactccccc gtatgcccca gctgcctgcc 52440 cgccaggccc gccaccgccc ccatgtcctt ccacccagac gcgcgcccct ctaccgacgg 52500 agcccgcgtt cccccccgcc gccaccggat cccaaccgga ggcatccaac gcggaggccg 52560 gggcccttgt caacgccagc agcgcagcac acgtggacgt tgacacggcc cgcgccgccg 52620 atttgttcgt ctctcagatg atgggggccc gctgattcgc cccggtcttt ggtaccatgg 52680 gatgtcttac tgtatatctt tttaaataaa ccaggtaata ccaaataaga cccattggtg 52740 tatgttcttt ttttattggg aggggcgggt aggcgggtag ctttacaatg caaaagcctt 52800 tgacgtggag gaaggcgtgg gggggaggaa atcggcactg accaaggggg tccgttttgt 52860 cacgggaaag gaaagaggaa acaggccgcg gacacccggg ggagtttatg tgttcctttt 52920 tctttcttcc cacacacaca caaaaggcgt accaaacaaa aaaaccaaaa gatgcgcatg 52980 cggtttaaca cccgtggttt ttatttacaa caaacccccc gtcacaggtc gtcctcgtcg 53040 gcgtcaccgt ctttgttggg aacttgggtg tagttggtgt tgcggcgctt gcgcatgacc 53100 atgtcggtga ccttggcgct gagcagcgcg ctcgtgccct tcttcttggc cttgtgttcc 53160 gtgcgctcca tggccgacac cagggccatg taccgtatca tctccctggc ctcggctagc 53220 ttggcctcgt caaagtcgcc gccctcctcg ccctccccgg acgcgtccgg gttggtgggg 53280 ttcttgagct ccttggtggt tagagggtac agggccttca tggggttgct ctgcagccgc 53340 atgacgtaac gaaaggcgaa gaaggccgcc gccaggccgg ccaggaccaa cagacccacg 53400 gccagcgccc caaaggggtt ggacatgaag gaggacacgc ccgacacggc cgataccacg 53460 ccgcccacga tgcccatcac caccttgccg accgcgcgcc ccaggtcgcc catcccctcg 53520 aagaacgcgc ccaggcccgc gaacatggcg gcgttggcgt cggcgtggat gaccgtgtcg 53580 atgtcggcga agcgcaggtc gtgcagctgg ttgcggcgct ggacctccgt gtagtccagc 53640 aggccgctgt ccttgatctc gtggcgggtg tacacctcca gggggacaaa ctcgtgatcc 53700 tccagcatgg tgatgttgag gtcgatgaag gtgctgacgg tggtgatgtc ggcgcggctc 53760 agctggtggg agtacgcgta ctcctcgaag tacacgtagc ccccaccgaa ggtgaagtag 53820 cgccggtgtc ccacggtgca cggctcgatc gcatcgcgcg tcagccgcag ctcgttgttc 53880 tcccccagct gcccctcgac caacgggccc tggtcttcgt accgaaagct gaccaggggg 53940 cggctgtagc aggccccggg ccgcgagctg atgcgcatcg agttttggac gatcacgttg 54000 tccgcggcga ccggcacgca cgtggagacg gccatcacgt cgccgagcat ccgcgcgctc 54060 acccgccggc ccacggtgac cgaggcgatg gcgttggggt tcagcttgcg ggcctcgttc 54120 cacagggtca gctcgtgatt ctgtagctcg caccacgcga tggcaacgcg gcccaacata 54180 tcgttgacat ggcgctgtat gtggttgtac gtaaactgca gccgggcgaa ctcgatggag 54240 gaggtggtct tgatgcgctc cacggacgcg ttggcgctgg ccccgggcgg cgggggcgtg 54300 gggtttgggg gcttgcggct ctgctctcgg aggtgttccc gcacgtacag ctccgcgagc 54360 gtgttgctga gaaggggctg gtacgcgatc agaaagcccc cattggccag gtagtactgc 54420 ggctggccca ccttgatgtg cgtcgcgttg tacctgcggg cgaagatgcg gtccatggcg 54480 tcgcgggcgt ccttgccgat gcagtccccc aggtccacgc gcgagagcgg gtactcggtc 54540 aggttggtgg tgaaggtggt ggatatggcg tcggaggaga atcggaagga gccgccgtac 54600 tcggagcgca gcatctcgtc cacttcctgc cacttggtca tggtgcagac cgacgggcgc 54660 tttggcaccc agtcccaggc cacggtgaac ttgggggtcg tgagcaggtt ccgggtggtc 54720 ggcgccgtgg cccgggcctt ggtggtgagg tcgcgcgcgt agaagccgtc gacctgcttg 54780 aagcggtcgg cggcgtagct ggtgtgttcg gtgtgcgacc cctcccggta gccgtaaaac 54840 ggggacatgt acacaaagtc gccagtcgcc agcacaaact cgtcgtacgg gtacaccgag 54900 cgcgcgtcca cctcctcgac gatgcagttt accgtcgtcc cgtaccggtg gaacgcctcc 54960 acccgcgagg ggttgtactt gaggtcggtg gtgtgccagc cccggctcgt gcgggtcgcg 55020 gcgttggccg gtttcagctc catgtcggtc tcgtggtcgt cccggtgaaa cgcggtggtc 55080 tccaggttgt tgcgcacgta cttggccgtg gaccgacaga cccccttggc gttgatcttg 55140 tcgatcacct cctcgaaggg gacgggggcg cggtcctcaa agatccccat aaactgggag 55200 tagcggtggc cgaaccacac ctgcgaaacg gtgacgtctt tgtagtacat ggtggccttg 55260 aacttgtacg gggcgatgtt ctccttgaag accaccgcga tgccctccgt gtagttctga 55320 ccctcgggcc gggtcgggca gcggcgcggc tgctcgaact gcaccaccgt ggcgcccgtg 55380 gggggtgggc acacgtaaaa gtttgcatcg gtgttctccg ccttgatgtc ccgcaggtgc 55440 tcgcgcaggg tggcgtggcc cgcggcgacg gtcgcgttgt cgccggcggg gcgtggtggc 55500 gttgggtttt tcggtttttt gttcttcttc ggtttcgggt cccccgttgg ggcggcgcca 55560 agggcgggcg gcgccggagt ggcagggccc ccgttcgccg cctgggtcgc ggccgcgacc 55620 ccaggcgtgc cgggggaact cggagccgcc gacgccacca ggacccccag cgtcaacccc 55680 aagagcgccc atacgacgaa ccaccggcgc ccccacgagg gggcgccctg gtgcatggcg 55740 ggactacggg ggcccgtcgt gccccccgtc aggtagcctg ggggcgaggt gctggaggac 55800 cgagtagagg atcgagaaaa cgtcgcggtc gtagaccacg accgaccggg ggccgataca 55860 gccgtcgggg gcgctctcga cgatggccac cagcggacag tcggagtcgt acgtgagata 55920 tacgccgggc gggtaacggt aacgaccttc ggaggtcggg cggctgcagt ccgggcggcg 55980 caactcgagc tccccgcacc ggtagaccga ggcaaagagt gtggtggcga taatcagctc 56040 gcgaatatat cgccaggcgg cgcgctgagt gggcgttatt ccggaaatgc cgtcaaaaca 56100 gtaaaacctc tgaaattcgc tgacggccca atcagcaccc gagccccccg cccccatgat 56160 gaaccgggcg agctcctcct tcaggtgcgg caggagcccc acgttctcga cgctgtaata 56220 cagcgcggtg ttggggggct gggcgaagct gtgggtggag tgatcaaaga ggggcccgtt 56280 gacgagctcg aagaagcgat gggtgatgct ggggagcagg gccgggtcca cctggtgtcg 56340 caggagagac gctcgcatga accggtgcgc gtcgaacacg cccggcgccg agcggttgtc 56400 gatgaccgtg cccgcgcccg ccgtcagggc gcagaagcgc gcgcgcgccg caaagccgtt 56460 ggcgaccgcg gcgaacgtcg cgggcagcac ctcgccgtgg acgctgaccc gcagcatctt 56520 ctcgagctcc ccgcgctgct cgcggacgca gcgccccagg ctggccaacg accgcttcgt 56580 caggcggtcc gcgtacagcc gccgtcgctc ccgtacgtcc gcggccgctt gcgtggcgat 56640 gtccccccac gtctcgggcc cctgcccccc gggcccgcgg cgacggtctt cgtcctcgcc 56700 cccgcccccg ggagctccca acccccgtgc cccttcctct acggcgacac ggtccccgtc 56760 gtcgtcgggg cccgcgccgc ccttgggcgc gtccgccgcg ccccccgccc ccatgcgcgc 56820 cagcacgcga cgcagcgcct cctcgtcgca ctgttcgggg ctgacgaggc gccgcaagag 56880 cggcgtcgtc aggtggtggt cgtagcacgc gcggatgagc gcctcgatct gatcgtcggg 56940 tgacgtggcc tgaccgccga ttattagggc gtccaccata tccagcgccg ccaggtggct 57000 cccgaacgcg cgatcgaaat gctccgcccg ccgcccgaac agcgccagtt ccacggccac 57060 cgcggcggtc tcctgctgca actcgcgccg cgccagcgcg gtcaggttgc tggcaaacgc 57120 gtccatggtg gtctggccgg cgcggtcgcc ggacgcgagc cagaatcgca attcgctgat 57180 ggcgtacagg ccgggcgtgg tggcctgaaa cacgtcgtgc gcctccagca gggcgtcggc 57240 ctccttgcgg accgagtcgt tctcgggcga cgggtggggc tgcccgtcgc cccccgcggt 57300 ccgggccagc gcatggtcca acacggagag cgcccgcgcg cggtcggcgt ccgacagccc 57360 ggcggcgtgg ggcaggtacc gccgcagctc gttggcgtcc agccgcacct gcgcctgctg 57420 ggtgacgtgg ttacagatac ggtccgccag gcggcgggcg atcgtcgccc cctggttcgc 57480 cgtcacacac agttcctcga aacagaccgc gcaggggtgg gacgggtcgc taagctccgg 57540 ggggacgata aggcccgacc ccaccgcccc caccataaac tcccgaacgc gctccagcgc 57600 ggcggtggcg ccgcgcgagg gggtgatgag gtggcagtag tttagctgct ttagaaagtt 57660 ctcgacgtcg tgcaggaaac acagctccat atggacggtc ccgccatacg tatccagcct 57720 gacccgttgg tgatacggac agggtcgggc caggcccatg gtctcggtga aaaacgccgc 57780 gacgtctccc gcggtcgcga acgtctccag gctgcccagg agccgctcgc cctcgcgcca 57840 cgcgtactct agcagcaact ccagggtgac cgacagcggg gtgagaaagg ccccggcctg 57900 ggcctccagg cccggcctca gacgacgccg cagcgcccgc acctgaagcg cgttcagctt 57960 cagttggggg agcttccccc gtccgatgtg ggggtcgcac cgccggagca gctctatctg 58020 aaacacatag gtctgcacct gcccgagcag ggctaacaac ttttgacggg ccacggtggg 58080 ctcggacacc ggggcggcca tctcgcggcg ccgatctgta ccgcggccgg agtatgcggt 58140 ggaccgaggc ggtccgtacg ctacccggtg tctggctgag ccccggggtc cccctcttcg 58200 gggcggcctc ccgcgggccc gccgaccggc aagccgggag tcggcggcgc gtgcgtttct 58260 gttctattcc cagacaccgc ggagaggaat cacggcccgc ccagagatat agacacggaa 58320 cacaaacaag cacggatgtc gtagcaataa tttattttac acacattccc cgccccgccc 58380 taggttcccc caccccccaa cccctcacag catatccaac gtcaggtctc cctttttgtc 58440 ggggggcccc tccccaaacg ggtcatcccc gtggaacgcc cgtttgcggc cggcaaatgc 58500 cggtcccggg gcccccgggc cgccgaacgg cgtcgcgttg tcgtcctcgc agccaaaatc 58560 cccaaagtta aacacctccc cggcgttgcc gagttggctg actagggcct cggcctcgtg 58620 cgccacctcc agggccgcgt ccgtcgacca ctcgccgttg ccgcgctcca gggcacgcgc 58680 ggtcagctcc atcatctcct cgcttaggta ctcgtcctcc aggagcgcca gccagtcctc 58740 gatctgcagc tgctgggtgc ggggccccag gcttttcacg gtcgccacga acacgctact 58800 ggcgacggcc gccccgccct cggagataat gccccggagc tgctcgcaca gcgagctttc 58860 gtgcgctccg ccgccgaggt tcgaggccgc gcacacaaac ccggcccggg gacaggccag 58920 gacgaacttg cgggtgcggt caaaaataag gagcgggcac gcgtttttgc cgcccatcag 58980 gctggcccag ttcccggcct gaaacacacg gtcgttgccg gccatgccgt agtatttgct 59040 gatgctcaac cccaacacga ccatggggcg cgccgccatg acgggccgca gcaggttgca 59100 gctggcgaac atggacgtcc acgcgcccgg atgcgcgtcc acggcgtcca tcagcgcgcg 59160 ggccccggcc tccaggcccg ccccgccctg cgcggaccac gcggccgccg cctgcacgct 59220 ggggggacgg cgggaccccg cgatgatggc cgtgagggtg ttgatgaagt atgtcgagtg 59280 atcgcagtac cgcagaatct ggtttgccat gtagtacatc gccagctcgc tcacgttgtt 59340 gggggccagg ttaataaagt ttatcgcgcc gtagtccagg gaaaactttt taatgaacgc 59400 gatggtctcg atgtcctcgc gcgacaggag ccgggcggga agctggttgc gttggagggc 59460 cgtccagaac cactgcgggt tcggctggtt ggaccccggg ggcttgccgt tggggaagat 59520 ggccgcgtgg aactgcttca gcagaaagcc cagcggtccg aggaggatgt ccacgcgctt 59580 gtcgggcttc tggtaggcgc tctggaggct ggcgacccgc gccttggcgg cctcggacgc 59640 gttggcgctc gcgcccgcga acaacacgcg gctcttgacg cgcagctcct tgggaaaccc 59700 cagggtcacg cgggcaacgt cgccctcgaa gctgctctcg gcgggggccg tctggccggc 59760 cgttaggctg ggggcgcaga tagccgcccc ctccgagagc gcgaccgtca gcgttttggc 59820 cgacagaaac ccgttgttaa acatgtccat cacgcgccgc cgcagcaccg gttggaattg 59880 attgcgaaag ttgcgcccct cgaccgactg cccggcgaac accccgtggc actggctcag 59940 ggccaggtcc tgatacacgg cgaggttgga tcgccgcccg agaagctgaa gcagggggca 60000 tggcccgcac gcgtacgggt ccagcgtcag ggacatggcg tggttggcct cgcccagacc 60060 gtcgcgaaac ttgaagttcc tcccctccac caggttgcgc atcagctgct ccacctcgcg 60120 gtccacgacc tgcctgacgt tgttcaccac cgtatgcagg gcctcgcggt tggtgatgat 60180 ggtctccagc cgccccatgg ccgtggggac cgcctggtcc acgtactgca gggtctcgag 60240 ttcggccatg acgcgctcgg tcgccgcgcg gtacgtctcc tgcatgatgg tccgggcggt 60300 ctcggatccg tccgcgcgct tcagggccga gaaggcggcg tagtttccca gcacgtcgca 60360 gtcgctgtac atgctgttca tggtcccgaa gacgccgatg gctccgcggg cggcgctggc 60420 gaacttggga tggcgcgccc ggaggcgcat gagcgtcgtg tgtacgcagg cgtggcgcgt 60480 gtcgaaggtg cacaggttgc agggcacgtc ggtctggttg gagtccgcga cgtatcgaaa 60540 cacgtccatc tcctggcgcc cgacgatcac gccgccgtcg cagcgctcca ggtaaaacag 60600 catcttggcc agcagcgccg gggaaaaccc acacagcatg gccaggtgct cgccggcaaa 60660 ttcctgggtt ccgccgacga ggggcgcggt gggccgaccc tcgaacccgg gcaccacgtg 60720 tccctcgcgg tccacctgtg ggttggccgc cacgtgggtc ccgggcacga ggaagaagcg 60780 gtaaaaggag ggtttgctgt ggtcctttgg gtccgccgga ccggcgtcgt ccacctcggt 60840 gagatggagg gccgagttgg tgctaaatac catggccccc acgagtcccg cggcgcgcgc 60900 caggtacgcc ccgacggcgt tggcgcgggc cgcggccgtg tcctggccct cgcacagcgg 60960 ccacgcggag atgtcggtgg gcggctcgtc gaagacggcc atcgacacga tagactcgag 61020 ggccagggcg gcgtctccgg ccatgacgga ggccaggcgc tgttcgaacc cgcccgccgg 61080 gcccttgccg ccgccgtcgc gcccaccccg cggggtctta ccctggctgg cttcgaaggc 61140 cgtgaacgta atgtcggcgg ggagggcggc gccctcgtgg ttttcgtcaa acgccaggtg 61200 ggcggccgcg cgggccacgg cgtccacgtt tcggcatcgc agtgccacgg cggcgggtcc 61260 cacgaccgcc tcgaacagga ggcggttgag ggggcggtta aaaaacggaa gcgggtaggt 61320 aaaattctcc ccgatcgatc ggtggttggc gttgaacggc tcggcgatga cccggctaaa 61380 atccggcatg aacagctgca acggatacac gggtatgcgg tgcacctccg ccccgcctat 61440 ggttaccttg tccgagcctc ccaggtgcag aaaggtgttg ttgatgcaca cggcctcctt 61500 gaagccctcg gtaacgacca gatacaggag ggcgcggtcc gggtccaggc cgaggcgctc 61560 acacagcgcc tcccccgtcg tctcgtgttt gaggtcgccg ggccgggggg tgtagtccga 61620 aaagccaaaa tggcggcgtg cccgctcgca gagtcgcgtc aggtttgggg cctgggtgct 61680 ggggtccagg tgccggccgc cgtgaaagac gtacacggac gagctgtagt gcgatggcgt 61740 cagtttcagg gacaccgcgg tacccccgag ccccgtcgtg cgagaaccca cgaccacggc 61800 tacgttggcc tcaaagccgc tctccacggt caggcccacg accaggggcg ccacggcgac 61860 gtcggcatcg ccgctgcgcg ccgacagtaa cgccagaagc tcgatgcctt cggacggaca 61920 cgcgcgagcg tacacgtatc ccaggggccc gggggggacc ttgatggtgg ttgccgtctt 61980 gggctttgtc tccatgtcct cctggcaatc ggtccgcaaa cggaggtaat cccggcacga 62040 cgacggacgc ccgacgaggt atgtctcccg agcgtcaaaa tccggggggg ggggcggcga 62100 cggtcaaggg gagggtggga gaccggggtt ggggaatgaa tccctaccct tcacagacaa 62160 cccccgggta accacggggt gccgatgaac cccggcggct ggcaacgcgg ggtccctgcg 62220 agaggcacag atgcttacgg tcaggtgctc cgggccgggt gcgtctgata tgcggttggt 62280 atatgtacac tttacctggg ggcgtgccgg accgccccag cccctcccac accccgcgcg 62340 tcatcagccg gtgggcgtgg ccgctattat aaaaaaagtg agaacgcgaa gcgttcgcac 62400 tttgtcctaa taatatatat attattagga caaagtgcga acgcttcgcg ttctcacttt 62460 ttttataata gcggccacgc ccaccggcta cgtcacgctc ctgtcggccg ccggcggtcc 62520 ataagcccgg ccggccgggc cgacgcgaat aaaccgggcc gccggccggg gcgccgcgca 62580 gcagctcgcc gcccggatcc gccagacaaa caaggccctt gcacatgccg gcccgggcga 62640 gcctgggggt ccggtaattt tgccatccca cccaagcggc ttttggggtt tttcctcttc 62700 ccccctcccc acatcccccc tctttagggg ttcgggtggg aacaaccgcg atgttttccg 62760 gtggcggcgg cccgctgtcc cccggaggaa agtcggcggc cagggcggcg tccgggtttt 62820 ttgcgcccgc cggccctcgc ggagccggcc ggggaccccc gccttgtttg aggcaaaact 62880 tttacaaccc ctacctcgcc ccagtcggga cgcaacagaa gccgaccggg ccaacccagc 62940 gccatacgta ctatagcgaa tgcgatgaat ttcgattcat cgccccgcgg gtgctggacg 63000 aggatgcccc cccggagaag cgcgccgggg tgcacgacgg tcacctcaag cgcgccccca 63060 aggtgtactg cgggggggac gagcgcgacg tcctccgcgt cgggtcgggc ggcttctggc 63120 cgcggcgctc gcgcctgtgg ggcggcgtgg accacgcccc ggcggggttc aaccccaccg 63180 tcaccgtctt tcacgtgtac gacatcctgg agaacgtgga gcacgcgtac ggcatgcgcg 63240 cggcccagtt ccacgcgcgg tttatggacg ccatcacacc gacggggacc gtcatcacgc 63300 tcctgggcct gactccggaa ggccaccggg tggccgttca cgtttacggc acgcggcagt 63360 acttttacat gaacaaggag gaggttgaca ggcacctaca atgccgcgcc ccacgagatc 63420 tctgcgagcg catggccgcg gccctgcgcg agtccccggg cgcgtcgttc cgcggcatct 63480 ccgcggacca cttcgaggcg gaggtggtgg agcgcaccga cgtgtactac tacgagacgc 63540 gccccgctct gttttaccgc gtctacgtcc gaagcgggcg cgtgctgtcg tacctgtgcg 63600 acaacttctg cccggccatc aagaagtacg agggtggggt cgacgccacc acccggttca 63660 tcctggacaa ccccgggttc gtcaccttcg gctggtaccg tctcaaaccg ggccggaaca 63720 acacgctagc ccagccgcgg gccccgatgg ccttcgggac atccagcgac gtcgagttta 63780 actgtacggc ggacaacctg gccatcgagg ggggcatgag cgacctaccg gcatacaagc 63840 tcatgtgctt cgatatcgaa tgcaaggcgg ggggggagga cgagctggcc tttccggtgg 63900 ccgggcaccc ggaggacctg gttattcaga tatcctgtct gctctacgac ctgtccacca 63960 ccgccctgga gcacgtcctc ctgttttcgc tcggttcctg cgacctcccc gaatcccacc 64020 tgaacgagct ggcggccagg ggcctgccca cgcccgtggt tctggaattc gacagcgaat 64080 tcgagatgct gttggccttc atgacccttg tgaaacagta cggccccgag ttcgtgaccg 64140 ggtacaacat catcaacttc gactggccct tcttgctggc caagctgacg gacatttaca 64200 aggtccccct ggacgggtac ggccgcatga acggccgggg cgtgtttcgc gtgtgggaca 64260 taggccagag ccacttccag aagcgcagca agataaaggt gaacggcatg gtgaacatcg 64320 acatgtacgg gatcataacc gacaagatca agctctcgag ctacaagctc aacgccgtgg 64380 ccgaagccgt cctgaaggac aagaagaagg acctgagcta tcgcgacatc cccgcctact 64440 acgccaccgg gcccgcgcaa cgcggggtga tcggcgagta ctgcatacag gattccctgc 64500 tggtgggcca gctgtttttt aagtttttgc cccatctgga gctctcggcc gtcgcgcgct 64560 tggcgggtat taacatcacc cgcaccatct acgacggcca gcagatccgc gtctttacgt 64620 gcctgctgcg cctggccgac cagaagggct ttattctgcc ggacacccag gggcgattta 64680 ggggcgccgg gggggaggcg cccaagcgtc cggccgcagc ccgggaggac gaggagcggc 64740 cagaggagga gggggaggac gaggacgaac gcgaggaggg cgggggcgag cgggagccgg 64800 agggcgcgcg ggagaccgcc ggccggcacg tggggtacca gggggccagg gtccttgacc 64860 ccacttccgg gtttcacgtg aaccccgtgg tggtgttcga ctttgccagc ctgtacccca 64920 gcatcatcca ggcccacaac ctgtgcttca gcacgctctc cctgagggcc gacgcagtgg 64980 cgcacctgga ggcgggcaag gactacctgg agatcgaggt gggggggcga cggctgttct 65040 tcgtcaaggc tcacgtgcga gagagcctcc tcagcatcct cctgcgggac tggctcgcca 65100 tgcgaaagca gatccgctcg cggattcccc agagcagccc cgaggaggcc gtgctcctgg 65160 acaagcagca ggccgccatc aaggtcgtgt gtaactcggt gtacgggttc acgggagtgc 65220 agcacggact cctgccgtgc ctgcacgttg ccgcgacggt gacgaccatc ggccgcgaga 65280 tgctgctcgc gacccgcgag tacgtccacg cgcgctgggc ggccttcgaa cagctcctgg 65340 ccgatttccc ggaggcggcc gacatgcgcg cccccgggcc ctattccatg cgcatcatct 65400 acggggacac ggactccata tttgtgctgt gccgcggcct cacggccgcc gggctgacgg 65460 ccatgggcga caagatggcg agccacatct cgcgcgcgct gtttctgccc cccatcaaac 65520 tcgagtgcga aaagacgttc accaagctgc tgctgatcgc caagaaaaag tacatcggcg 65580 tcatctacgg gggtaagatg ctcatcaagg gcgtggatct ggtgcgcaaa aacaactgcg 65640 cgtttatcaa ccgcacctcc agggccctgg tcgacctgct gttttacgac gataccgtat 65700 ccggagcggc cgccgcgtta gccgagcgcc ccgcagagga gtggctggcg cgacccctgc 65760 ccgagggact gcaggcgttc ggggccgtcc tcgtagacgc ccatcggcgc atcaccgacc 65820 cggagaggga catccaggac tttgtcctca ccgccgaact gagcagacac ccgcgcgcgt 65880 acaccaacaa gcgcctggcc cacctgacgg tgtattacaa gctcatggcc cgccgcgcgc 65940 aggtcccgtc catcaaggac cggatcccgt acgtgatcgt ggcccagacc cgcgaggtag 66000 aggagacggt cgcgcggctg gccgccctcc gcgagctaga cgccgccgcc ccaggggacg 66060 agcccgcccc ccccgcggcc ctgccctccc cggccaagcg cccccgggag acgccgtcgc 66120 atgccgaccc cccgggaggc gcgtccaagc cccgcaagct gctggtgtcc gagctggccg 66180 aggatcccgc atacgccatt gcccacggcg tcgccctgaa cacggactat tacttctccc 66240 acctgttggg ggcggcgtgc gtgacattca aggccctgtt tgggaataac gccaagatca 66300 ccgagagtct gttaaaaagg tttattcccg aagtgtggca ccccccggac gacgtggccg 66360 cgcggctccg ggccgcaggg ttcggggcgg tgggtgccgg cgctacggcg gaggaaactc 66420 gtcgaatgtt gcatagagcc tttgatactc tagcatgagc cccccgtcga agctgatgtc 66480 cctcatttta caataaatgt ctgcggccga cacggtcgga atctccgcgt ccgtgggttt 66540 ctctgcgttg cgccggacca cgagcacaaa cgtgctctgc cacacgtggg cgacgaaccg 66600 gtaccccggg cacgcggtga gcatccggtc tatgagccgg tagtgcaggt gggcggacgt 66660 gccgggaaag atgacgtaca gcatgtggcc cccgtaagtg gggtccgggt aaaacaacag 66720 ccgcgggtcg cacgccccgc ctccgcgcag gatcgtgtgg acgaaaaaaa gctcgggttg 66780 gccaagaatc ccggccaaga ggtcctggag gggggcgttg tggcggtcgg ccaacacgac 66840 caaggaggcc aggaaggcgc gatgctcgaa tatcgtgttg atctgctgca cgaaggccag 66900 gattagggcc tcgcggctgg tggcggcgaa ccgcccgtct cccgcgttgc acgcgggaca 66960 gcaacccccg atgcctaggt agtagcccat cccggagagg gtcaggcagt tgtcggccac 67020 ggtctggtcc agacagaagg gcagcgacac gggagtggtc ttcaccaggg gcaccgagaa 67080 cgagcgcacg atggcgatct cctcggaggg cgtctgggcg agggcggcga aaaggccccg 67140 atagcgctgg cgctcgtgta aacacagctc ctgtttgcgg gcgtgaggcg gcaggctctt 67200 ccgggaggcc cgacgcacca cgcccagagt cccgccggcc gcagaggagc acgaccgccg 67260 gcgctccttg ccgtgatagg gcccgggccg ggagccgcgg cgatgggggt cggtatcata 67320 cataggtaca cagggtgtgc tccagggaca ggagcgagat cgagtggcgt ctaagcagcg 67380 cgcccgcctc acggacaaat gtggcgagcg cggtgggctt tggtacaaat acctgatacg 67440 tcttgaaggt gtagatgagg gcacgcaacg ctatgcagac acgcccctcg aactcgttcc 67500 cgcaggccag cttggccttg tggagcagca gctcgtcggg atgggtggcg gggggatggc 67560 cgaacagaac ccaggggtca acctccatct ccgtgatggc gcacatgggg tcacagaaca 67620 tgtgcttaaa gatggcctcg ggccccgcgg cccgcagcag gctcacaaac cggcccccgt 67680 ccccgggctg cgtctcgggg tccgcctcga gctggtcgac gacgggtacg atacagtcga 67740 agaggctcgt gttgttttcc gagtagcgga ccacggaggc ccggagtctg cgcagggcca 67800 gccagtaagc ccgcaccagt aacaggttac acagcaggca ttctccgccg gtgcgcccgc 67860 gcccccggcc gtgtttcagc acggtggcca tcagagggcc caggtcgagg tcgggctggg 67920 catcgggttc ggtaaactgc gcaaagcgcg gagccacgtc gcgcgtgcgt gccccgcgat 67980 gcgcttccca ggactggcgg accgtggcgc gacgggcctc cgcggcagcg cgcagctggg 68040 gccccgactc ccagacggcg ggggtgccgg cgaggagcag caggaccaga tccgcgtacg 68100 cccacgtatc cggcgactcc tccggctcgc ggtccccggc gaccgtctcg aattccccgt 68160 tgcgagcggc ggcgcgcgta cagcagctgt ccccgccccc gcgccgaccc tccgtgcagt 68220 ccaggagacg ggcgcaatcc ttccagttca tcagcgcggt ggtgagcgac ggctgcgtgc 68280 cggatcccgc cgccgacccc gccccctcct cgcccccgga ggccaaggtt ccgatgaggg 68340 cccgggtggc agactgcgcc aggaacgagt agttggagta ctgcaccttg gcggctcccg 68400 gggagggcga gggcttgggt tgcttctggg catgccgccc gggcaccccg ccgtcggtac 68460 ggaagcagca gtggagaaaa aagtgccggt ggatgtcgtt tatggtgagg gcaaagcgtg 68520 cgaaggagcc gaccagggtc gccttcttgg tgcgcagaaa gtggcggtcc atgacgtaca 68580 caaactcgaa cgcggccacg aagatgctag cggcgcagtg gggcgccccc aggcatttgg 68640 cacagagaaa cgcgtaatcg gccacccact ggggcgagag gcggtaggtt tgcttgtaca 68700 gctcgatggt gcggcagacc agacagggcc ggtccagcgc gaaggtgtcg atggccgccg 68760 cggaaaaggg cccggtgtcc aaaagcccct ccccacaggg atccgggggc gggttgcggg 68820 gtcctccgcg cccgcccgaa ccccctccgt cgcccgcccc cccgcgggcc cttgaggggg 68880 cggtgaccac gtcggcggcg acgtcctcgt cgagcgtacc gacgggcggc acacctatca 68940 cgtgactggc cgccaggagc tcggcgcaga gagcctcgtt aagagccagg aggctgggat 69000 cgaaggccac atacgcgcgc tcgaacgccc ccgccttcca gctgctgccg ggggactctt 69060 cgcacaccgc gacgctcgcc aggaccccgg ggggcgaagt tgccatggct gggcgggagg 69120 ggcgcacgcg ccagcgaact ttacgggaca caatccccga ctgcgcgctg cggtcccaga 69180 ccctggagag tctagacgcg cgctacgtct cgcgagacgg cgcgcatgac gcggccgtct 69240 ggttcgagga tatgaccccc gccgagctgg aggttgtctt cccgactacg gacgccaagc 69300 tgaactacct gtcgcggacg cagcggctgg cctccctcct gacgtacgcc gggcctataa 69360 aagcgcccga cgacgccgcc gccccgcaga ccccggacac cgcgtgtgtg cacggcgagc 69420 tgctcgcccg caagcgggaa agattcgcgg cggtcattaa ccggttcctg gacctgcacc 69480 agattctgcg gggctgacgc gcgcgctgtt gggcgggacg gttcgcgaac cctttggtgg 69540 gtttacgcgg gcacgcacgc tcccatcgcg ggcgccatgg cgggactggg caagccctac 69600 cccggccacc caggtgacgc cttcgagggt ctcgttcagc gaattcggct tatcgtccca 69660 tctacgttgc ggggcgggga cggggaggcg ggcccctact ctccctccag cctcccctcc 69720 aggtgcgcct ttcagtttca tggccatgac gggtccgacg agtcgtttcc catcgagtat 69780 gtactgcggc ttatgaacga ctgggccgag gtcccgtgca acccttacct gcgcatacag 69840 aacaccggcg tgtcggtgct gtttcagggg ttttttcatc gcccacacaa cgcccccggg 69900 ggcgcgatta cgccagagcg gaccaatgtg atcctgggct ccaccgagac gacggggctg 69960 tccctcggcg acctggacac catcaagggg cggctcggcc tggatgcccg gccgatgatg 70020 gccagcatgt ggatcagctg ctttgtgcgc atgccccgcg tgcagctcgc gtttcggttc 70080 atgggccccg aagatgccgg acggacgaga cggatcctgt gccgcgccgc cgagcaggct 70140 attacccgtc gccgccgaac ccggcggtcc cgggaggcgt acggggccga ggccgggctg 70200 ggggtggctg gaacgggttt ccgggccagg ggggacggtt ttggcccgct ccccttgtta 70260 acccaagggc cctcccgccc gtggcaccag gccctgcggg gtcttaagca cctacggatt 70320 ggcccccccg cgctcgtttt ggcggcggga ctcgtcctgg gggccgctat ttggtgggtg 70380 gttggtgctg gcgcgcgcct ataaaaaagg acgcaccgcc gccctaatcg ccagtgcgtt 70440 ccggacgcct tcgccccaca cagccctccc gtccgacacc cccatatcgc ttcccgacct 70500 ccggtcccga tggccgtccc gcaatttcac cgccccagca ccgttaccac cgatagcgtc 70560 cgggcgcttg gcatgcgcgg gctcgtcttg gccaccaata actctcagtt tatcatggat 70620 aacaaccacc cgcaccccca gggcacccaa ggggccgtgc gggagtttct ccgcggtcag 70680 gcggcggcgc tgacggacct tggtctggcc cacgcaaaca acacgtttac cccgcagcct 70740 atgttcgcgg gcgacgcccc ggccgcctgg ttgcggcccg cgtttggcct gcggcgcacc 70800 tattcaccgt ttgtcgttcg agaaccttcg acgcccggga ccccgtgagg cccggggagt 70860 tccttctggg gtgttttaat caataaaaga ccacaccaac gcacgagcct tgcgtttaat 70920 gtcgtgttta ttcaagggag tgggataggg ttcgacggtt cgaaacttaa cacacaaaat 70980 aatcgagcgc gtctagccca gtaacatgcg cacgtgatgt aggctggtca gcacggcgtc 71040 gctgtgatga agcagcgccc ggcgggtccg ctgtaactgc tgttgtaggc ggtaacaggc 71100 gcggatcagc accgccaggg cgctacgacc ggtgcgttgc acgtagcgtc gcgacagaac 71160 tgcgtttgcc gatacgggcg gggggccgaa ttgtaagcgc gtcacctctt gggagtcatc 71220 ggcggataac gcactgaatg gttcgttggt tatgggggag tgtggttccc gagggagtgg 71280 gtcgagcgcc tcggcctcgg aatccgagag gaacaacgag gtggtgtcgg agtcttcgtc 71340 gtcagagaca tacagggtct gaagcagcga cacgggcggg ggggtagcgt caatgtgtag 71400 cgcgagggag gatgcccacg aagacacccc agacaaggag ctgcccgtgc gtggatttgt 71460 ggacgacgcg gaagccggga cggatgggcg gttttgcggt gcccggaacc gaaccgccgg 71520 atactccccg ggtgctacat gcccgttttg gggctggggt tggggctggg gctggggttg 71580 gggttggggc tggggttggg gctggggttg gggctggggt tggggttggg gttggggctg 71640 gggttggggt tggggctggg gctggggctg gggctggggc tggggctggg gctggggctg 71700 gggctggggc tggggctggg gctggggctg gggctggggt tggggctggg gttggggctg 71760 gggcgcggac aggcggttga cggtcaaatg cccccggggg cgcgcagatg tggtgggcgt 71820 ggccaccggc tgccgtgtag tggggcggcg ggaaaccggg cctccgggcg taacaccgcc 71880 ctccagcgtc aagtatgtgg ggggcgggcc tgacgtcggg ggcggggtga cgggttggac 71940 cgcgggaggc gggggagagg gacctgcggg agaggatgag gtcggctcgg ccgggttgcg 72000 gcctaaaaca ggggccgtgg ggtcggcggg gtcccagggt gaagggaggg attcccgcga 72060 ttcggacagc gacgcgacag cggggcgcgt aaggcgccgc tgcggcccgc ctacgggaac 72120 cctggggggg gttggcgcgg gacccgaggt tagcgggggg cggcggtttt cgcccccggg 72180 caaaaccgtg ccggttgcga ccgggggcgg aacgggatcg atagggagag cgggagaagc 72240 ctggccggcg aactggggac cgagcgggag gggcacacca gacaccaaag cgtggagcgc 72300 tggctctggg ggtttgggag gggccggggg gcgcgcgaaa tcggtaaccg gggcgaccgt 72360 gtcggggagg gcaggcggcc gccaaccctg ggtggtcgcg gaagcctggg tggcgcgcgc 72420 cagggagcgt gcccggcggt gtcggcgcgc gcgcgacccg gacgaagaag cggcagaagc 72480 gcgggaggag gcgggggggc ggggggcggt ggcatcgggg ggcgccgggg aactttgggg 72540 ggacggcaag cgccggaagt cgtcgcgggg gcccacgggc gccggccgcg tgctttcggc 72600 cgggacgccc ggtcgtgctt cgcgagccgt gactgccggc ccagggggcc gcggtgcaca 72660 ctgggacgtg gggacggact gatcggcggt gggcgaaagg gggtccgggg caaggagggg 72720 cgcggggccg ccggagtcgt cagacgcgag ctcctccagg ccgtgaatcc atgcccacat 72780 gcgagggggg acgggctcgc cgggggtggc gtcggtgaat agcgtggggg ccaggcttcc 72840 gggccccaac gagccctccg tcccaacaag gtccgccggg ccgggggtcg ggttcgggac 72900 cgaggggctc tggtcgtcgg gggcgcgctg gtacaccgga tgccccggga atagctcccc 72960 cgacaggagg gaggcgtcga acggccgccc gaggatagct cgcgcgagga aggggtcctc 73020 gtcggtggcg ctggcggcga ggacgtcctc gccgcccgcc acaaacggga gctcctcggt 73080 ggcctcgctg ccaacaaacc gcacgtcggg ggggccgggg gggtccgggt tttcccacaa 73140 caccgcgacc ggggtcatgg agatgtccac gagcaccaga cacggcgggc cccgggcgag 73200 gggccgctcg gcgatgagcg cggacaggcg cgggagctgt gccgccagac acgcgttttc 73260 aatcgggttc aggtcggcgt gcaggaggcg gacggcccac gtctcgatgt cggacgacac 73320 ggcatcgcgc aaggcggcgt ccggcccgcg agcgcgtgag tcaaacagcg tgagacacag 73380 ctccagctcc gactcgcggg aaaaggccgt ggtgttgcgg agcgccacga cgacgggcgc 73440 gcccaggagc actgccgcca gcaccaggtc catggccgta acgcgcgccg cgggggtgcg 73500 gtgggtggcg gcggccggca cggcgacgtg ctggcccgtg ggccggtaga gggcgttggg 73560 gggagcgggg ggtgacgcct cgcgcccccc cgaggggctc agcgtctgcc cagattccag 73620 acgcgcggtc agaagggcgt cgaaactgtc atactctgtg tagtcgtccg gaaacatgca 73680 ggtccaaaga gcggccagag cggtgcttgg gagacacatg cgcccgagga cgctcaccgc 73740 cgccagcgcc tgggcgggac tcagctttcc cagcgcggcg ccgcgctcgg ttcccagctc 73800 ggggaccgag cgccagggcg ccagggggtc ggtttcggac aacttgccgc ggcgccagtc 73860 tgccagccgc gtgccgaaca tgaggccccg ggtcggaggg cctccggtcg aaaacactgg 73920 cagcacgcgg atgcgggcgt ctggatgcgg ggtcaggcgc tgcacgaata gcatggaatc 73980 tgctgcgttc tgaaacgcac gggggagggt gagatgcatg tactcgtgtt ggcggaccag 74040 atccaggcgc caaaaggtgt aaatgtgttc cggggagctg gccaccagcg ccaccagcac 74100 gtcgttctcg ttaaaggaaa cgcggtgcct agtggagctg tggggcccga gcggcggtcc 74160 cggggccgcc gcgtcacccc cccattccag ctgggcccag cgacacccaa actcgcgcgt 74220 gagagtggtc gcgacgaggg cgacgtagag ctcggccgcc gcatccatcg aggcccccca 74280 tctcgcctgg cggtggcgca caaagcgtcc gaagagctga aagttggcgg cctgggcgtc 74340 gctgagggcc agctgaagcc ggttgatgac ggtgatgacg tacatggccg tgacggtcga 74400 ggccgactcc agggtgtccg tcggaagcgg ggggcgaatg catgccgcct cgggacacat 74460 cagcagcgcg ccgagcttgt cggtcacggc cgggaagcag agcgcgtact gcagtggcgt 74520 tccatccggg accaaaaagc tgggggcgaa cggccgatcc agcgtactgg tggcctcgcg 74580 cagcaccagg ggccccgggc ctccgctcac tcgcaggtac gcctcgcccc ggcggcgcag 74640 catctgcggg tcggcctctt ggccgggtgg ggcggacgcc cgggcgcggg cgtctagggc 74700 gcgaagatcc acgagcaggg gcgcgggcgc ggcggccgcg cccgcgcccg tctggcctgt 74760 ggccttggcg tacgcgctat ataagcccat gcggcgttgg atgagctccc gcgcgccccg 74820 gaactcctcc accgcccatg gggccaggtc cccggccacc gcgtcgaatt ccgccaacag 74880 gccccccagg gtgtcaaagt tcatctccca ggccaccctt ggcaccacct cgtcccgcag 74940 ccgggcgctc aggtcggcgt gttgggccac gcgccccccg agctcctcca cggccccggc 75000 ccgctcggcg ctcttggcgc ccaggacgcc ctggtacttg gcgggaaggc gctcgtagtc 75060 ccgctgggct cgcagccccg acacagtgtt ggtggtgtcc tgcagggcgc gaagctgctc 75120 gcatgccgcg cgaaatccct cgggcgattt ccaggccccc ccgcgaacgc ggccgaagcg 75180 accccatacc tcgtcccact ccgcctcggc ctcctcgaga gacctccgca gggcctcgac 75240 gcggcgacgg gtgtcgaaga gcgcctgcag gcgcgcgccc tgtcgcgtca ggaggcccgg 75300 gccgtcgccg ctggccgcgt ttagcgggtg cgtctcaaag gtacgctggg catgttccaa 75360 ccaggcgacc gcctgcacgt cgagctcgcg cgccttctcc gtctggtcca acagaatttc 75420 gacctgatcc gcgatctcct ccgccgagcg cgcctggtcc agcgtcttgg ccacggtcgc 75480 cgggacggcg accaccttca gcagggtctt cagattggcc agaccctcgg cctcgagctg 75540 ggcccggcgc tcgcgcgcgg ccagcacctc ccgcagcccc gccgtgaccc gctcggtggc 75600 ttcggcgcgc tgctgtttgg cgcgcaccac ggcgtccttg gtatcggcca ggtcctgtcg 75660 ggtcacgaat gcgacgtagt cggcgtacgc cgtgtccttc acggggctct ggtccacgcg 75720 ctccagcgcc gccacgcacg ccaccagcgc gtcctcgctc gggcagggca gggtgacccc 75780 tgcccggaca agctcggcgg ccgccgccgg gtcgttgcgc accgcggata tctcctccgc 75840 ggcggcggcc aggtccagcg ccacgcttcc gatcgcgcgc cgcgcgtcgg cccggagggc 75900 gtccaggcga tcgcggatat ccacgtactc ggcgtagccc ttttgaaaaa acggcacgta 75960 ctggcgcagg gccggcacgc cccccaagtc ttccgacagg tgtaggacgg cctcgtggta 76020 gtcgataaac ccgtcgttcg cctgggcccg ctccagcagc ccccccgcca gccgcagaag 76080 ccgcgccagg ggctcggtgt ccacccgaaa catgtcggcg tacgtgtcgg ccgcggcccc 76140 gaaggccgcg ctccagtcga tgcggtgaat ggctgcgagc ggggggagca tggggtggcg 76200 ctggttctcg ggggtgtatg ggttaaacgc aagggccgtc tccagggcaa gggtcaccgc 76260 cttggcgttg gttcccagcg cctgttcggc ccgctttcgg aagtcccggg ggttgtagcc 76320 gtgcgtgccc gccagcgcct gcaggcgacg gagctcgacc acgtcaaact cggcaccgct 76380 ttccacgcgg tccagcacgg cctccacgtc ggcggcccag cgctcgtggc tactgcgggc 76440 gcgctgggcc gccatcttct ctctcaggtc ggcgatggcg gcctcaagtt cgtcggcgcg 76500 gcgtcgcgtg gcgccgatga cctttcccag ctcctgcagg gcgcgcccgc tgggggagtg 76560 gtccccggcc gtcccttcgg cgtgcaacag gcccccgaac ctgccctcgt ggcccgcgag 76620 gctttcccgc gcgccggtgg tcgcgcgcgt cgcggcctgg atcagggagg catgctctcc 76680 ctccggttgg ttggcggccc ggcgcacctg gacgacaagg tcggctgccg ccgaccctaa 76740 ggtcgtgagc tgggcgatgg ccccccgcgc gtccagggcc aaccgagtcg ccttgacgta 76800 tcccgcggcg ctgtcggcca tggccgctag gaaggccagg ggggaggccg ggtcgctggc 76860 ggccgcgccc agggccgtca ccgcgtcgac caggacgcgg tgcgcccgca cggccgcatc 76920 caccgtcgac gcggggtctg ccgtcgcgac ggcggcgctg ccggcgttga tggcgttcga 76980 gacggcgtgg gctatgatcg gggcgtgatc ggcgaagaac tgcaagagaa acggagtctc 77040 tggggcgtcg gcgaacaggt tcttcagcac caccacgaag ctgggatgca agccagacag 77100 agccgtcgcc gtgtccggag tcgggtgctc cagggcatct cggtactgcc ccagcagccc 77160 ccacatgtcc gcccgcagcg ccgccgtaac ctcagggggc gccccccgaa cggcctcggg 77220 gaggtccgac cagcccgccg gcagggaggc ccgcagggtc gccaggacgg ccggacaggc 77280 ctttagcccc acaaagtcag ggagggggcg caggaccccc tggagtttgt gcaagaactt 77340 ctcccgggcg tcgcgggcca ccttcgcccg ctcccgcgct ccctcgagca ttgcctccag 77400 ggagcgcgcg cgctcccgca aacgggcacg cgcatcgggg gcgagctctg ccgtcagctt 77460 ggcggcatcc atggcccgcg cctgccgcag cgcttcctcg gccatgcgcg tggcctctgg 77520 cgacagcccg ccgtcgtcgg ggtagggcga cgcgccgggc gcaggaacaa aggccgcgtc 77580 gctgtccagc tgctggccca gggccgcatc tagggcgtcg aagcgccgca gctcggccag 77640 acccgagctg cggcgcgcct gctggtcgtt aatgtcgcgg atgctgcgcg ccagctcgtc 77700 cagcggcttg cgttctatca gcccttggtt ggcggcgtcc gtcaggacgg agagccaggc 77760 cgccaggtcc tcgggggcgt ccagcgtctg gccccgctgg atcagatccc gcaacaggat 77820 ggccgtgggg ctggtcgcga tcgggggcgg ggcgggaatg gcggcgcgct gcgcgatgtc 77880 ccgcgtgtgc tggtcgaaga caggcaggga ctcgagcagc tggaccacgg gcacgacggc 77940 ggccgaagcc acgtgaaacc ggcggtcgtt gttgtcgctg gcctgtagag ccttggcgct 78000 gtatacggcc ccccggtaaa agtactcctt aaccgcgccc tcgatcgccc gacgggcctg 78060 ggtccgcacc tcctccagcc gaacctgaac ggcctcgggg cccagggggg gtgggcgcgg 78120 agccccctgc ggggccgccc cggccggggc gggcattacg ccgaggggcc cggcgtgctg 78180 tgagaccgcg tcgaccccgc gagcgagggc gtcgagggcc tcgcgcatct ggcgatcctc 78240 cgcctccacc ctaatctctt cgccacgggc aaatttggcc agagcctgga ctctatacag 78300 aagcggttct gggtgcgtcg gggtggcggg ggcaaaaagg gtgtccgggt gggcctgcga 78360 gcgctccaga agccactcgc cgaggcgtgt atacagattg gccggcgggg ccgcgcgaag 78420 ctgcagctcc aggtccgcga gttccccgta aaaggcgtcc gtctcccgaa tgacatccct 78480 agccacaagg atcagcttcg ccagcgccag gcgaccgatc agagagtttt cgtccagcac 78540 gtgctggacg aggggcagat gggcggccac gtcggccagg ctcaggcgcg tggaggccag 78600 aaagtccccc acggccgttt tccggggcag catgctcagg gtaaactcca gcagggcggc 78660 ggccgggccg gccaccccgg cctgggtgtg cgtccgggcc ccgttctcga tgagaaaggc 78720 gaggacgcgt tcaaagaaaa aaataacaca gagctccagc agccccggag aagccggata 78780 cggcgaccgt aaggcgctga tggtgagccg cgaacacgcg gcgacctcgc gggccagggt 78840 ggcggagcac gcggtgaact taaccgccgt ggcggccacg tttgggtggg cctcgaacag 78900 ctgggcgagg tctgcgcccg ggggctcggg tgagcggcga gtcttcagcg cctcgagggc 78960 ctgtgaggac gccggaacca tgggcccgtc gtcctcgccc gcctcggcga ccggcggccc 79020 ggccgggtcg gggggtgccg aggcgaggac aggctccgga acggaggcgg ggaccgcggc 79080 cccgacgggg gttttgcctt tgggggtgga tttcttcttg gttttggcag ggggggccga 79140 gcgtttcgtt ttctcccccg aagtcaggtc ttcgacgctg gaaggcggag tccaggtggg 79200 tcggcggcgc ttgggaaggc cggccgagta gcgtgcccgg tgccgaccaa ccgggacgac 79260 gcccatctcc aggacccgca tgtcgtcgtc atcttcttcg gccgcctctg cggcgggggt 79320 cttgggggcg gagggaggcg gtggtgggat cgcggagggt gggtcggcgg aggggggatc 79380 cgtgggtggg gtacccttta gggccaccgc ccatacatcg tcgggcgccc gattcgggcg 79440 cttggcctct ggttttgccg acggaccggc cgtcccccgg gatgtctcgg aggccctgtc 79500 gtcgcgacgg gcccgggtcg gtggcggcga ctgggcggct gtgggcgggt gtggccccgg 79560 cccccctccc ccctcccggg ggcccacgcc gacgcagggc tcccccaggc ccgcgatctc 79620 gccccgcagg gggtgcgtga tggccacgcg ccgttcgctg aacgcttcgt cctgcatgta 79680 agtctcgctg gccccgtaaa gatgcagagc cgcggccgtc aagtccgcag gagccgcggg 79740 ttccgggccc gacggcacga aaaacaccat ggctcccgcc caccgtacgt ccgggcgatc 79800 gcgggtgtaa tacgtcaggt atggatacat gtcccccgcc cgcactttgg cgatgaacgc 79860 gggggtgccc tccggaaggc catgcgggtc aaaaaggtat gcggtgtcgc cgtccctgaa 79920 cagccccatc cctagggggc caatggttag gagcgtgtac gacagggggc gcagggccca 79980 cgggccggcg aagaacgtgt gtgcggggca ttgtgtctcc agcaggcctg ccgcgggctc 80040 cccgaagaag cccacctcgc cgtatacgcg cgagaagaca cagcgcagtc cgccgcgcgc 80100 ccctgggtac tcgaggaagt tggggagctc gacgatcgaa cacatgcgcg gcggcccagg 80160 gcccgcagtc gcgcgcgtcc actcgccccc ctcgaccaaa catccctcga tggcctccgc 80220 ggacagaacg tcgcgagggc ccacatcaaa tatgaggctg agaaaggaca gcgacgagcg 80280 catgcacgat accgaccccc ccggctccag gtcgggcgcg aactggttcc gagcaccggt 80340 gaccacgatg tcgcgatccc ccccgcgttc catcgtggag tgcggtgggg tgcccgcgat 80400 catatgtgcc ctgcgggcca gagacccggc ctgtttatgg accggacccc cggggttagt 80460 gttgtttccg ccacccacgc ccccgtacca tggccccggt tcccctgatt aggctacgag 80520 tcgcggtgat cgcttcccaa aaaccgagct gcgtttgtct gtcttggtct tccccccccc 80580 cagcccgcac accataacac cgagaacaac acacgggggt gggcggaaca taataaagct 80640 ttattggtaa ctagttaacg gcaagtccgt gggtggcgcg acggtgtcct ccgggatcat 80700 ctcgtcgtcc tcgacggggg tgttggaatg aggcgcctcc tcgcggtcca cctggcgtgg 80760 gccgtgccca taggcctccg gcttctgtgc gtccatgggc gtaggcgcgg ggagactgtt 80820 tccggcgtcg cggacctcca ggtccctggg agcctccggt ccggctaacg gacgaaacgc 80880 ggaagcgcga aacacgccgt cggtgacccg caggagctcg ttcatcagta accaatccat 80940 actcagcgta acggccagcc cctggcgaga cagatccacg gagtccggaa ccgcggtcgt 81000 ctggcccagg gggccgaggc tgtagtcccc ccaggcccct aggtcgcgac ggctcgtaag 81060 cacgacgcgg tcggccgcgg ggctttgcgg gggggcgtcc tcgggcgcat gcgccattac 81120 ctctcggatg gccgcggcgc gctggtcggc cgagctgacc aagggcgcca cgaccacggc 81180 gcgctccgtc tgcaggccct tccacgtgtc gtggagttcc tggacaaact cggccacggg 81240 ctcgggtccc gcggccgcgc gcgcggcttg atagcaggcc gacagacgcc gccagcgcgc 81300 tagaaactga cccatgaaac aaaacccggg gacctggtct cccgacagca gcttcgacgc 81360 ccgggcgtga atgccggaca cgacggacag aaacccgtga atttcgcgcc ggaccacggc 81420 cagcacgttg tcctcgtgcg acacctgggc cgccagctcg tcgcacaccc ccaggtgcgc 81480 cgtggtttcg gtgatgacgg aacgcaggct cgcgagggac gcgaccagcg cgcgcttggc 81540 gtcgtgatac atgctgcagt actgactcac cgcgtccccc atggcctcgg ggggccaggg 81600 ccccaggcgg tcgggcgtgt ccccgaccac cgcatacagg cggcgcccgt cgctctcgaa 81660 ccgacactcg aaaaaggcgg agagcgtgcg catgtgcagc cgcagcagca cgatggcgtc 81720 ctccagttgg cgaatcaggg ggtcggcgcg ctcggcgagg tcctgcagca ccccccgggc 81780 agccagggcg tacatgctaa tcaacaggag gctggtgccc acctcggggg gcgggggggg 81840 ctgcagttgg accaggggcc gcagctgctc gacggcaccc ctggagatca cgtacagctc 81900 ccggagcagc tgctctatgt tgtcggccat ctgcatagtg gggccgaggc cgccccgggc 81960 ggccggttcg aggagagtga tcagcgcgcc cagtttggtg cgatggccct cgaccgtggg 82020 gagatagccc agcccaaagt cccgggccca ggccaacaca cgcagggcga actcgaccgg 82080 gcggggaagg taggccgcgc tacacgtggc cctcagcgcg tccccaacca ccagggccag 82140 aacgtagggg acgaagcccg ggtcggcgag gacgttgggg tgaatgccct cgagggcggg 82200 gaagcggatc tgggtcgccg cggccaggtg gacagagggg gcatggctgg gctgcccgac 82260 ggggagaagc gcggacagcg gcgtggccgg ggtggtgggg gtgatgtccc agtgggtctg 82320 accatacacg tcgatccaga tgagcgccgt ctcgcggaga aggctgggtt gaccggaact 82380 aaagcggcgc tcggccgtct caaactcccc cacgagcgcc cgccgcaggc tcgccagatg 82440 ttccgtcggc acggccggcc ccatgatacg cgccagcgtc tggctcagaa cgccccccga 82500 caggccgacc gcctcacaga gccgcccgtg cgtgtgctcg ctggcgccct ggacccgcct 82560 gaaagttttt acgtagttgg catagtaccc gtattcccgc gccagaccaa acacgttcga 82620 ccccgcgagg gcaatgcacc caaagagctg ctggacttcg ccgagtccgt ggccggcggg 82680 cgtccgcgcg gggacgcccg ccgccagaaa cccctccagg gccgaaaggt agtgcgtgca 82740 gtgcgagggc gtgaacccag cgtcgatcag ggtgttgatc accacggagg gcgaattggt 82800 attctggatc aacgtccacg tctgctgcag cagagccagc agccgctgct gggcgccggc 82860 ggagggctgc tccccgagct gcagcaggct ggagacggca ggctggaaga ctgccagtgc 82920 cgacgaactc aggaacggca cgtcgggatc aaacacggcc acgtccgtcc gcacgcgcgc 82980 cattagcgtc cccgggggcg cacaggccga gcgcgggctg acgcggctga gggccgtcga 83040 cacgcgcacc tcctcgcggc tgcgaaccat cttgttggcc tccagtggcg gaatcattat 83100 ggccgggtcg atctcccgca cggtgtgctg aaactgcgcc aacaggggcg gcgggaccac 83160 agccccccgc tcgggggtcg tcaggtactc gtccaccagg gccaacgtaa agagggcccg 83220 tgtgagggga gtgagggtcg cgtcgtctat gcgctggagg tgcgccgaga acagcgtcac 83280 ccgattactc accagggcca agaaccggag gccctcttgc acgaacgggg cggggaagag 83340 caggctgtac gccggggtgg taaggttcgc gctgggctgc cccaacggga ccggcgccag 83400 cttgagcgac gtctccccaa gggcctcgat ggaggtccgc gggctcatgg ccaagcagct 83460 cttggtgacg gtttgccagc ggtctatcca ctccacggcg cactggcgga cgcggaccgg 83520 ccccagggcc gccgcggtgc gcaggccggc ggactccagc gcatgggacg tgtcggagcc 83580 ggtgaccgcg aggatggtgt ccttgatgac ctccatctcc cggaaggcct ggtcgggggc 83640 ctcggggaga gccaccacca agcggtgtac gagcaacccg gggaggttct cggccaagag 83700 cgccgtctcc ggaagcccgt gggcccggtg gagcgcgcac aggtgttcca gcagcggccg 83760 ccagcatgcc cgcgcgtctg ccggggcgat ggccgttccc gacaacagaa acgccgccat 83820 ggcggcgcgc agcttggccg tggccagaaa cgccgggtcg tccgccccgt ttgccgtctc 83880 ggccgtgggg gttggcggtt ggcgaaggcc ggctaggctc gccaataggc gctgcatagg 83940 tccgtccgag ggcggaccgg cgggtgaggt cgtgacgacg ggggcctcgg acgggagacc 84000 gcggtctgcc atgacgcccg gctcgcgtgg gtgggggaca gcgtagacca acgacgagac 84060 cgggcgggaa tgactgtcgt gcgctgtagg gagcggcgaa ttatcgatcc cccgcggccc 84120 tccaggaacc ccgcaggcgt tgcgagtacc ccgcgtcttc gcggggtgtt atacggccac 84180 ttaagtcccg gcatcccgtt cgcggaccca ggcccggggg attgtccgga tgtgcgggca 84240 gcccggacgg cgtgggttgc ggactttcgg cggggcggcc caaatggccc tttaaacgtg 84300 tgtatacgga cgcgccgggc cagtcggcca acacaaccca ccggaggcgg tagccgcgtt 84360 tggctgtggg gtgggtggtt ccgccttgcg tgagtgtcct ttcgaccccc cccctccccc 84420 gggtcttgct aggtcgcgat ctgtggtcgc aatgaagacc aatccgctac ccgcaacccc 84480 ttccgtgtgg ggcgggagta ccgtggaact cccccccacc acacgcgata ccgcggggca 84540 gggcctgctt cggcgcgtcc tgcgcccccc gatctctcgc cgcgacggcc cagtgctccc 84600 cagggggtcg ggaccccgga gggcggccag cacgctgtgg ttgcttggcc tggacggcac 84660 agacgcgccc cctggggcgc tgacccccaa cgacgatacc gaacaggccc tggacaagat 84720 cctgcggggc accatgcgcg ggggggcggc cctgatcggc tccccgcgcc atcatctaac 84780 ccgccaagtg atcctgacgg atctgtgcca acccaacgcg gatcgtgccg ggacgctgct 84840 tctggcgctg cggcaccccg ccgacctgcc tcacctggcc caccagcgcg ccccgccagg 84900 ccggcagacc gagcggctgg gcgaggcctg gggccagctg atggaggcga ccgccctggg 84960 gtcggggcga gccgagagcg ggtgcacgcg cgcgggcctc gtgtcgttta acttcctggt 85020 ggcggcgtgt gccgcctcgt acgacgcgcg cgacgccgcc gatgcggtac gggcccacgt 85080 cacggccaac taccgcggga cgcgggtggg ggcgcgcctg gatcgttttt ccgagtgtct 85140 gcgcgccatg gttcacacgc acgtcttccc ccacgaggtc atgcggtttt tcggggggct 85200 ggtgtcgtgg gtcacccagg acgagctagc gagcgtcacc gccgtgtgcg ccgggcccca 85260 ggaggcggcg cacaccggcc acccgggccg gccccgctcg gccgtgatcc tcccggcgtg 85320 tgcgttcgtg gacctggacg ccgagctggg gctggggggc ccgggcgcgg cgtttctgta 85380 cctggtattc acttaccgcc agcgccggga ccaggagctg tgttgtgtgt acgtgatcaa 85440 gagccagctc cccccgcgcg ggttggagcc ggccctggag cggctgtttg ggcgcctccg 85500 gatcaccaac acgattcacg gcaccgagga catgacgccc ccggccccaa accgaaaccc 85560 cgacttcccc ctcgcgggcc tggccgccaa tccccaaacc ccgcgttgct ctgctggcca 85620 ggtcacgaac ccccagttcg ccgacaggct gtaccgctgg cagccggacc tgcgggggcg 85680 ccccaccgca cgcacctgta cgtacgccgc ctttgcagag ctcggcatga tgcccgagga 85740 tagtccccgc tgcctgcacc gcaccgagcg ctttggggcg gtcagcgtcc ccgttgtcat 85800 cctggaaggc gtggtgtggc gccccggcga gtggcgggcc tgcgcgtgag cgtagcaaac 85860 gccccgccca cacaacgctc cgcccccaac cccttccccg ctgtcactcg ttgttcgttg 85920 acccggacgt ccgccaaata aagccactga aacccgaaac gcgagtgttg taacgtcctt 85980 tgggcgggag gaagccacaa aatgcaaatg ggatacatgg aaggaacaca cccccgtgac 86040 tcaggacatc ggcgtgtcct tttgggtttc actgaaactg gcccgcgccc cacccctgcg 86100 cgatgtggat aaaaagccag cgcgggtggt ttagggtacc acaggtgggt gctttggaaa 86160 cttgtcggtc gccgtgctcc tgtgagcttg cgtccctccc cggtttcctt tgcgctcccg 86220 ccttccggac ctgctctcgc ctatcttctt tggctctcgg tgcgattcgt caggcagtgg 86280 ccttgtcgaa tctcgacccc accactcgcc ggacccgccg acgtcccctc tcgagcccgc 86340 cgaaacccgc cgcgtctgtt gaaatggcca gccgccccgc cgcatcctct cccgtcgaag 86400 cgcgggcccc ggttggggga caggaggccg gcggccccag cgcagccacc cagggggagg 86460 ccgccggggc ccctctcgcc cgcggccacc acgtgtactg ccagcgagtc aatggcgtga 86520 tggtgctttc cgacaagacg cccgggtccg cgtcctaccg catcagcgat agcaactttg 86580 tccaatgtgg ttccaactgc accatgatca tagacggaga cgtggtgcgc gggcgccccc 86640 aggacccggg ggccgcggca tcccccgctc ccttcgttgc ggtgacaaac atcggagccg 86700 gcagcgacgg cgggaccgcc gtcgtggcat tcgggggaac cccacgtcgc tcggcgggga 86760 cgtctaccgg tacccagacg accgacgtcc ccaccgaggc ccttgggggc ccccctcctc 86820 ctccccgctt caccctgggt ggcggctgtt gttcctgtcg cgacacacgg cgccgctctg 86880 cggtattcgg gggggagggg ccatagccaa tccatgaccc tgtatgtcac ggagaaggcg 86940 gacgggaccc tcccagcctc caccctggtc cgccttctgg tccacgcata taagcgcgga 87000 ctaaaaacag ggatgtacta ctgcaaggtt cgcaaggcga ccaacagcgg ggtctttggc 87060 ggcgacgaca acattgtctg cacgagctgc gcgctgtgac cgacaaaccc cctccgcgcc 87120 aggcccgccg ccactgtcgt cgccgtccca cgcgctcccc cgctgccatg gattccgcgg 87180 ccccagccct ctcccccgct ctgacggccc atacgggcca gagcgcgccg gcggacctgg 87240 cgatccagat tccaaagtgc cccgaccccg agaggtactt ctacacctcc cagtgtcccg 87300 acattaacca cctgcgctcc ctcagcatcc ttaaccgctg gctggaaacc gagcttgttt 87360 tcgtggggga cgaggaggac gtctccaagc tttccgaggg cgagctcagc ttttaccgct 87420 tcctcttcgc tttcctgtcg gccgccgacg acctggttac ggaaaacctg ggcggcctct 87480 ccggcctgtt tgagcagaag gacattctcc actactacgt ggagcaggaa tgcatcgaag 87540 tcgtacactc gcgcgtgtac aacatcatcc agctggtgct ttttcacaac aacgaccagg 87600 cgcgccgcga gtacgtggcc ggcaccatca accacccggc catccgcgcc aaggtggact 87660 ggctggaagc gcgggtgcgg gaatgcgcct ccgttccgga aaagttcatc ctcatgatcc 87720 tcatcgaggg catctttttt gccgcctcgt ttgccgccat cgcctacctt cgcaccaaca 87780 accttctgcg ggtcacctgc cagtcaaacg acctcatcag ccgggacgag gccgtgcaca 87840 cgacggcctc gtgttacatc tacaacaact acctcggcgg gcacgccaag cccccgcccg 87900 accgcgtgta cgggctgttc cgccaggcgg tcgagatcga gatcggattt atccgatccc 87960 aggcgccgac ggacagccat atcctgagcc cggcggcgct ggcggccatc gaaaactacg 88020 tgcgattcag cgcggatcgc ctgttgggcc ttatccacat gaagccactg ttttccgccc 88080 caccccccga cgccagcttt ccgctgagcc tcatgtccac cgacaaacac accaattttt 88140 tcgagtgtcg cagcacctcc tacgccgggg cggtcgtcaa cgatctgtga gggtcgcggc 88200 gcgcttctac ccgtgtttgc ccataataaa cctctgaacc aaactttggg tctcattgtg 88260 attcttgtca gggacgcggg ggtgggagag gataaaaggc ggcgcaaaaa gcagtaacca 88320 ggtccgtcca gattctgagg gcataggata ccataatttt attggtgggt cgtttgttcg 88380 gggacaagcg cgctcgtctg acgtttgggc tactcgtccc agaatttggc caggacgtcc 88440 ttgtagaacg cgggtggggg ggcctgggtc cgcagctgct ccagaaacct gtcggcgata 88500 tcaggggccg tgatatgccg ggtcacaata gatcgcgcca ggttttcgtc gcggatgtcc 88560 tggtagatag gcaggcgttt cagaagagtc cacggccccc gctccttggg gccgataagc 88620 gatatgacgt acttaatgta gcggtgttcc accagctcgg tgatggtcat gggatcgggg 88680 agccagtcca gggactctgg ggcgtcgtgg atgacgtggc gtcgccggct ggccacataa 88740 ctgcggtgct cttccagcag ctgcgcgttc gggacctgga cgagctcggg cggggtgagt 88800 atctccgagg aggacgacct ggggccgggg tggcccccgg taacgtcccg gggatccagg 88860 gggaggtcct cgtcgtcttc gtatccgccg gcgatctgtt gggttagaat ttcggtccac 88920 gagacgcgca tctcggtgcc gccggcggcc ggcggcaaag ggggcctggt ttccgtggag 88980 cgcgagctgg tgtgttcccg gcggatggcc cgccgggtct gagagcgact cgggggggtc 89040 cagtgacatt cgcgcagcac atcctccacg gaggcgtagg tgttattggg atggaggtcg 89100 gtgtggcagc ggacaaagag ggccaggaac tgggggtagc tcatcttaaa gtactttagt 89160 atatcgcgac agttgatcgt gggaatgtag caggcgctaa tatccaacac aatatcacag 89220 cccatcaaca ggaggtcagt gtctgtggtg tacacgtacg cgaccgtgtt ggtgtgatag 89280 aggttggcgc aggcatcgtc cgcctccagc tgacccgagt taatgtaggc gtaccccagg 89340 gcccggagaa cgcgaataca gaacagatgc gccagacgca gggccggctt cgagggcgcg 89400 gcggacggca gcgcggctcc ggacccggcc gtcccccggg tccccgaggc cagagaggtg 89460 ccgcgccggc gcatgttgga aaaggcagag ctgggtctgg agtcggtgat gggggaaggc 89520 ggtggagagg cgtccacgtc actggcctcc tcgtccgtcc ggcattgggc cgtcgtgcgg 89580 gccaggatgg ccttggctcc aaacacaacc ggctccatac aattgacccc gcgatcggta 89640 acgaagatgg ggaaaaggga cttttgggta aacaccttta ataagcgaca gaggcagtgt 89700 agcgtaatgg cctcgcggtc gtaactgggg tatcggcgct gatatttgac caccaacgtg 89760 tacatgacgt tccacaggtc cacggcgatg ggggtgaagt acccggccgg ggccccaagg 89820 ccctggcgct tgaccagatg gtgtgtgtgg gcaaacttca tcatcccgaa caaacccatg 89880 tcaggtcgat tgtaactgcg gatcggccta actaaggcgt ggttggtgcg acggtccggg 89940 acacccgagc ctgtctctct gtgtatggtg acccagacaa caacaccgac acaagaggac 90000 aataatccgt taggggacgc tctttataat ttcgatggcc caactccacg cggattggtg 90060 cagcaccctg catgcgccgg tgtgggccaa acttcccccc gctcattgcc tcttccaaaa 90120 gggtgtggcc taacgagctg ggggcgtatt taatcaggct agcgcggcgg gcctgccgta 90180 gtttctggct cggtgagcga cggtccggtt gcttgggtcc cctggctgcc agcaaaaccc 90240 caccctcgca gcggcatacg ccccctccgc gtcccgcacc cgagaccccg gcccggctgc 90300 cctcaccacc gaagcccacc tcgtcactgt ggggtgttcc cagcccgcat tgggatgacg 90360 gattcccctg gcggtgtggc ccccgcctcc cccgtggagg acgcgtcgga cgcgtccctc 90420 gggcagccgg aggagggggc gccctgccag gtggtcctgc agggcgccga acttaatgga 90480 atcctacagg cgtttgcccc gctgcgcacg agccttctgg actcgcttct ggttatgggc 90540 gaccggggca tccttatcca taacacgatc tttggggagc aggtgttcct gcccctggaa 90600 cactcgcaat tcagtcggta tcgctggcgc ggacccacgg cggcgttcct gtctctcgtg 90660 gaccagaagc gctccctcct gagcgtgttt cgcgccaacc agtacccgga cctacgtcgg 90720 gtggagttgg cgatcacggg ccaggccccg tttcgcacgc tggttcagcg catatggacg 90780 acgacgtccg acggcgaggc cgttgagcta gccagcgaga cgctgatgaa gcgcgaactg 90840 acgagctttg tggtgctggt tccccaggga acccccgacg ttcagttgcg cctgacgagg 90900 ccgcagctca ccaaggtcct taacgcgacc ggggccgata gtgccacgcc caccacgttc 90960 gagctcgggg ttaacggcaa attttccgtg ttcaccacga gtacctgcgt cacatttgct 91020 gcccgcgagg agggcgtgtc gtccagcacc agcacccagg tccagatcct gtccaacgcg 91080 ctcaccaagg cgggccaggc ggccgccaac gccaagacgg tgtacgggga aaatacccat 91140 cgcaccttct ctgtggtcgt cgacgattgc agcatgcggg cggtgctccg gcgactgcag 91200 gtcgccgggg gcaccctcaa gttcttcctc acgacccccg tccccagtct gtgcgtcacc 91260 gccaccggtc ccaacgcggt atcggcggta tttctcctga aaccccagaa gatttgcctg 91320 gactggctgg gtcatagcca ggggtctcct tcagccggga gctcggcctc ccgggcctct 91380 gggagcgagc caacagacag ccaggactcc gcgtcggacg cggtcagcca cggcgatccg 91440 gaagacctcg atggcgctgc ccgggcggga gaggcggggg cctcgcacgc ctgtccgatg 91500 ccgtcgtcga ccacgcgggt cactcccacg accaagcggg ggcgctcggg gggcgaggat 91560 gcgcgcgcgg acacggccct aaagaaacct aagacggggt cgcccaccgc acccccgccc 91620 acagatccag tccccctgga cacggaggac gactccgatg cggcggacgg gacggcggcc 91680 cgtcccgccg ctccagacgc ccggagcgga agccgttacg cgtgttactt tcgcgacctc 91740 ccgaccggag aagcaagccc cggcgccttc tccgccttcc gggggggccc ccaaaccccg 91800 tatggttttg gattcccctg acggggcggg gccttggcgg ccgcccaact ctcgcaccat 91860 cccgggttaa tgtaaataaa cttggtattg cccaacactc tcccgcgtgt cgcgtgtggt 91920 tcatgtgtgt gcctggcgtc ccccaccctc gggttcgtgt atttcctttc cctgtcctta 91980 taaaagccgt atgtggggcg ctgacggaac caccccgcgt gccatcacgg ccaaggcgcg 92040 ggatgctccg caacgacagc caccgggccg cgtccccgga ggacggccag ggacgggtcg 92100 acgacggacg gccacacctc gcgtgcgtgg gggccctggc gcgggggttc atgcatatct 92160 ggcttcaggc cgccacgctg ggttttgcgg gatcggtcgt tatgtcgcgc gggccgtacg 92220 cgaatgccgc gtctggggcg ttcgccgtcg ggtgcgccgt gctgggcttt atgcgcgcac 92280 cccctcccct cgcgcggccc accgcgcgga tatacgcctg gctcaaactg gcggccggtg 92340 gagcggccct tgttctgtgg agtctcgggg agcccggaac gcagccgggg gccccgggcc 92400 cggccaccca gtgcctggcg ctgggcgccg cctatgcggc gctcctggtg ctcgccgatg 92460 acgtctatcc gctctttctc ctcgccccgg ggcccctgtt cgtcggcacc ctggggatgg 92520 tcgtcggcgg gctgacgatc ggaggcagcg cgcgctactg gtggatcggt gggcccgccg 92580 cggccgcctt ggccgcggcg gtgttggcgg gcccgggggc gaccaccgcc agggactgct 92640 tctccagggc gtgccccgac caccgccgcg tctgcgtcat cgtcgcaggc gagtctgttt 92700 cccgccgccc cccggaggac ccagagcgac ccggggaccc cgggccaccg tcccccccga 92760 caccccaacg atcccagggg ccgccggccg atgaggtcgc accggccggg gtagcgcggc 92820 ccgaaaacgt ctgggtgccc gtggtcacct ttctgggggc gggcgcgctc gccgtcaaga 92880 cggtgcgaga acatgcccgg gaaacgccgg gcccgggcct gccgctgtgg ccccaggtgt 92940 ttctcggagg ccatgtggcg gtggccctga cggagctgtg tcaggcgctt atgccctggg 93000 accttacgga cccgctgctg tttgttcacg ccggactgca ggtcatcaac ctcgggttgg 93060 tgtttcggtt ttccgaggtt gtcgtgtatg cggcgctagg gggtgccgtg tggatttcgt 93120 tggcgcaggt gctggggctc cggcgtcgcc tgcacaggaa ggaccccggg gacggggccc 93180 ggttggcggc gacgcttcgg ggcctcttct tctccgtgta cgcgctgggg tttggggtgg 93240 gggcgctgct gtgccctccg gggtcaacgg gcgggtggtc gggcgattga tatatttttc 93300 aataaaaggc attagtcccg aagaccgccg gtgtgtgatg atttcgccat aacacccaaa 93360 ccccggatgg ggcccgggta taaattccgg aaggggacac gggctaccct cactaccgag 93420 ggcgcttggt cgggaggccg catcgaacgc acacccccat ccggtggtcc gtgtggaggt 93480 cgtttttcag tgcccggtct cgctttgccg ggaacgctag ccgatccctc gcgaggggga 93540 ggcgtcgggc atggccccgg ggcgggtggg ccttgccgtg gtcctgtgga gcctgttgtg 93600 gctcggggcg ggggtggccg ggggctcgga aactgcctcc accgggccca cgatcaccgc 93660 gggagcggtg acgaacgcga gcgaggcccc cacatcgggg tcccccgggt cagccgccag 93720 cccggaagtc acccccacat cgaccccaaa ccccaacaat gtcacacaaa acaaaaccac 93780 ccccaccgag ccggccagcc ccccaacaac ccccaagccc acctccacgc ccaaaagccc 93840 ccccacgtcc acccccgacc ccaaacccaa gaacaacacc acccccgcca agtcgggccg 93900 ccccactaaa ccccccgggc ccgtgtggtg cgaccgccgc gacccattgg cccggtacgg 93960 ctcgcgggtg cagatccgat gccggtttcg gaattccacc cgcatggagt tccgcctcca 94020 gatatggcgt tactccatgg gtccgtcccc cccaatcgct ccggctcccg acctagagga 94080 ggtcctgacg aacatcaccg ccccacccgg gggactcctg gtgtacgaca gcgcccccaa 94140 cctgacggac ccccacgtgc tctgggcgga gggggccggc ccgggcgccg accctccgtt 94200 gtattctgtc accgggccgc tgccgaccca gcggctgatt atcggcgagg tgacgcccgc 94260 gacccaggga atgtattact tggcctgggg ccggatggac agcccgcacg agtacgggac 94320 gtgggtgcgc gtccgcatgt tccgcccccc gtctctgacc ctccagcccc acgcggtgat 94380 ggagggtcag ccgttcaagg cgacgtgcac ggccgccgcc tactacccgc gtaaccccgt 94440 ggagtttgtc tggttcgagg acgaccgcca ggtgtttaac ccgggccaga tcgacacgca 94500 gacgcacgag caccccgacg ggttcaccac agtctctacc gtgacctccg aggctgtcgg 94560 cggccaggtc cccccgcgga ccttcacctg ccagatgacg tggcaccgcg actccgtgat 94620 gttctcgcga cgcaatgcca ccgggctggc cctggtgctg ccgcggccaa ccatcaccat 94680 ggaatttggg gtccggcatg tggtctgcac ggccggctgc gtccccgagg gcgtgacgtt 94740 tgcctggttc ctgggggacg acccctcacc ggcggctaag tcggccgtta cggcccagga 94800 gtcgtgcgac caccccgggc tggctacggt ccggtccacc ctgcccattt cgtacgacta 94860 cagcgagtac atctgtcggt tgaccggata tccggccggg attcccgttc tagagcacca 94920 cggcagtcac cagcccccac ccagggaccc caccgagcgg caggtgatcg aggcgatcga 94980 gtgggtgggg attggaatcg gggttctcgc ggcgggggtc ctggtcgtaa cggcaatcgt 95040 gtacgtcgtc cgcacatcac agtcgcggca gcgtcatcgg cggtaacgcg agaccccccc 95100 gttacctttt taatatctat atagtttggt ccccctctat cccgcccacc gctgggcgct 95160 ataaagccgc caccctctct tccctcaggt catccttggt cgatcccgaa cgacacacgg 95220 cgtggagcaa aacgcctccc cctgagccgc tttcctacca acacaacggc atgcctctgc 95280 gggcatcgga acacgcctac cggcccctgg gccccgggac accccccatg cgggctcggc 95340 tccccgccgc ggcctgggtt ggcgtcggga ccatcatcgg gggagttgtg atcattgccg 95400 cgttggtcct cgtgccctcg cgggcctcgt gggcactttc cccatgcgac agcggatggc 95460 acgagttcaa cctcgggtgc atatcctggg atccgacccc catggagcac gagcaggcgg 95520 tcggcggctg tagcgccccg gcgaccctga tcccccgcgc ggctgccaaa cagctggccg 95580 ccgtcgcacg cgtccagtcg gcaagatcct cgggctactg gtgggtgagc ggagacggca 95640 ttcgggcctg cctgcggctc gtcgacggcg tcggcggtat tgaccagttt tgcgaggagc 95700 ccgcccttcg catatgctac tatccccgca gtcccggggg ctttgttcag tttgtaactt 95760 cgacccgcaa cgcgctgggg ctgccgtgag gcgcgtgtac tgcggtctgt ctcgtctcct 95820 cttctcccct tccctccccc tccgcatccc aggatcacac cggccaacga gggttggggg 95880 ggtccggcac ggacccaaaa taataaacac acaatcacgt gcgataaaaa gaacacgcgg 95940 tcccctgtgg tgtttttggt tatttttatt aaatctcgtc gacaaacagg gggaaagggg 96000 cgtggtctag cgacggcagc acgggcggag gcgttcaccg gctccggcgt ccttcgcgtt 96060 taagcttggt caggagggcg ctcagggcgg cgacgttggt cgggccgtcg ttggtcaggg 96120 cgttggctcg atggcgggcg aggacgggcg aggggctcaa cggcgggggc gggggtccgg 96180 tgcggcccgg gggggaaaat agggcggatc ccccccagtc gtacagggga ttttccgcct 96240 caatgtacgg ggaggccggc gctgcattcg ccgtgttcac gcagacgttt tcgtagaccc 96300 gcatccatgg tatttcctcg tagacacgcc ccccgtcctc gctcacggtc tcgtatattg 96360 actcgtcgtc ctcgtagggg gcgtgccgtt cgcgggccga ggcggcgtgg gtggctttgc 96420 ggcgggcgtc gtcgtcgtcg tcgtcggccg tcagatacgt ggcttccatc tggtcgggtt 96480 ctccctccgg ggcgggtccc cacacccgtg gccgatcgag gctccccaga gacgcgcgcc 96540 ggacaagaag ggggcacgtc gccgccggcg gtcgcctgtc gggtcccgcg acgttacggg 96600 ccgggaggcg cgggggcacc tcccccatgt gcgtgtaata cgtggccggc tgtgcggccg 96660 cagcgggggg ctcggcgacc gggtcgtccg catccggaag cgggggcccc gcgccgtccg 96720 cacggcgcct ccggaaccgc cgggtggacg gcgcgggggt cgagtgtagg cgaggtcggg 96780 ggaggggcgg gggctcgttg tcgcgccgcg cccgctgaat cttttcccga caggtcccac 96840 cccccgcgcg atgccccccc gggccgcggg ccatgtcgtc cgggggaggc cccgcggacc 96900 acgtcgtccg gcgagacgcc acgagccgca ggatggactc gtagtggagc gacggcgccc 96960 cgctgcggag cagatccgcg gccagggcgg ccccgaacca agccttgatg ctcaactcca 97020 tccgggccca gctgggggcg gtcatcgtgg ggaacagggg ggcggtggtc cgacagaaac 97080 gctcctggct gtccaccgcg gcccgcagat actcgttgtt caggctgtcg gtggcccaga 97140 cgccgtaccc ggtgagggtc gcgttgatga tatactgggc gtggtgatgg acgatcgaca 97200 gaacctccac cgtggatacc acggtatcca cggtcccgta cgtaccgccg ctccgcttgc 97260 cggtctgcca caggttggct aggcacgtca ggtggcccag gacgtcgctg accgccgccc 97320 tgagcgccat gcactgcatg gagccggtcg tgccgctggg accccggtcc agatggcgcg 97380 cgaacgtttc cgcgggcgcc tccgggctgc cgccgagcgg gaggaaccgg cgattggagg 97440 gactcagccg gtgacatacg tgcttgtccg tcgtccacag catccaggac gcccaccggt 97500 acagcacgga gacgtaggcc aggagctcgt tgagccgcag tgcggtgtcg gtgctggggc 97560 ggcttgggtc cgccgggcgc ataaagaaca tgtactgctg aatccgatgg agggcgtcgc 97620 gcaggccggc cacggtggcg gcgtacttgg ccgccgcggc cccgctcttg aacggggtgc 97680 gcgccagcag ctttggcgcc agggtgggcc gcagcagcac gtgaaggctg gggtcgcagt 97740 cgcccacggg gtcctcgggg acgtccaggc cgctgggcac caccgtctgc aggtacttcc 97800 agtactgcgt gaggatggcg cggctcaact ggccgccggg cagctccacc tcgcccagcg 97860 cctgggtggc ggccgaagcg tagtgccgga tgtactcgta gtgcgggtcg ctggcgagcc 97920 cgtccacgat caaactctcg ggaaccgtgt tgtgttgccg cgcggccaac cggacgctgc 97980 gatcggtgca ggtcagaaac gccggctgcg cgtcgtcgga gcgctgccgc aaggcgccca 98040 cggccgcgct aaggagcccc tccggggtgg ggagcagaca cccgccgaag atgcgccgct 98100 cgggaacgcc cgcgttgtcg ccgcggatca ggttggcagg cgtcaggcac cgcgccagcc 98160 gcagggagct cgcgccgcgc gtccggcgct gcatggtgac gcccgttcgg tcgggacccg 98220 ccggtcggag ttatgccgcg tccagggcca tcggggcgct ttttatcggg aggagcttat 98280 gggcgtggcg ggcctcccag cccggtcgcg cgcctccccg acacgtgcgc ccgcagggcg 98340 gcggccccct cgtctcccat cagcagtttc ctaaactggg acatgatgtc caccacgcgg 98400 acccgcgggc ccaacacgga cccgccgctt acgggggcgg gggggaaggg ctccaggtcc 98460 ttgagcagaa aggcggggtc tgccgtcccg gacacggggg cccggggcgc ggaggaggcg 98520 gggcgcagat ccacgtgctc cgcggccgcg cggacgtccg cccagaactt ggcgggggtg 98580 gtgcgcgcgt acaggggctg ggtcgctcgg aggacacacg cgtagcgcag gggggtgtac 98640 gtgcccacct cgggggccgt gaatcccccg tcaaacgcgg ccagtgtcac gcacgccacc 98700 acggtgtcgg caaagcccag cagccgctgc aggacgagcc cggcggccag aatggcgcgc 98760 gtggtcgcag cgtcgtcccg gcgccggtgc gcgtccccgc acgcccgggc gtactttaag 98820 gtcactgtcg ccagggccgt gtgcagcgcg tacaccgcag cgcccagcac ggcgttgagc 98880 ccgctgttgg cgagcagccg gcgcgctgcg gtgtcgccca gcgcctcgtg ctcggccccc 98940 acgaccgcgg ggcttcccag gggcagggcg cgaaacagct cctcccgcgc cacgtccgca 99000 aaggcggggt ggtgcacgtg cgggtgcagg cgcgccccca cgaccaccga gagccactgg 99060 accgtctgct ccgccatcac cgccaacaca tccagcacgc gccccaggaa ggcggcctcc 99120 cgcgtcaaaa cgcaccggac ggcgtcggga ttgaagcggg cgagcagggc cccggtggcc 99180 aggtacgtca tgcggccggc atagcgggcg gccacgcgac agtcgcggtc cagcagcgcg 99240 cgcaccccgg gccagtacag cagggacccc agcgagctgc gaaacaccgc ggcgtcgggg 99300 ccggattggg gggacactaa cccccccgcg ctcagtaacg gcacggccgc ggccccgacg 99360 ggacgcaacg ccgtgaggct cgcgaactgc cgcctcagct cggcagccct gtcgtccagg 99420 tccgacccgc gcgcctctgc gtgaaggcgc gtcccgcaca cccacccgtt gatggccagc 99480 cgcacgacgg catccgccaa aaagctcatc gcctgggcgg ggctggtttt tgttcgacga 99540 tccgtcaggt caagaatccc atcgcccgtg atataccagg ccaacgcctc gccctgctgc 99600 agggtttggc ggaaaaacac cgcggggttg tcgggggagg cgaagtgcat gacccccacg 99660 cgcgataacc cgaacgcgct atccggacac gggtaaaacc cggccggatg ccccagggct 99720 agggcggagc gcacggactc gtcccacacg gcaacctgag gggccagtcg atccaacggg 99780 aatgccgccc ggagctccgg gcccggcacg cgtccctcca gaacctccac cttgggcggg 99840 gaacgggccc cgccgccgtc ctccggcccg acgtcttccg ggtagtcgtc ctcctcgtac 99900 tgcagttcct ctaggaacag cggcgacggc gccacccgcg aaccgccgac ccgccccaaa 99960 atagcccgcg cgtcgacggg acccaggtat cccccctgcc gggcctgcgg aggaccgcgg 100020 ggaacctcat catcatcgtc caggcgaccg cgcaccgact ggctacgggc cgcatcgggc 100080 ccggggcgct gccgggacgc tcggcgatgg gatgagggcg gggcttccga cgcgcgccgt 100140 cgtcgggctc gcgggccttc ccgtcgacgg cgcacgggcg gctcgtcgcc cgccatctcc 100200 tccagagcct ctagctcgct gtcgtcatcc ccgcggaaca ccgcacgcag gtaccccatg 100260 aaccccaccc catcgcccgc tggctcgtcc gccacgggcg aggcgcgggg gcgggtggat 100320 gcgcgcctcc tgcgccccgc gggttcgcga gccgacatgg tggcgataga cgcgggttat 100380 cggatgtccg ctacccccca aaaaagaaaa agaccccaca gcgcggatgg aggtcggggt 100440 aggtgccgcc ggaccccctc gcgatgggaa tggacgggag cgacggggcc ggcgcaaaaa 100500 acgcagtatc tcccgcgaag gctacccgcc gccccagccc ccggccaaat gcggaaacgg 100560 tcccgcgctc tcgcctttat acgcgggccg ccctgcgaca caatcacccg tccgtggttt 100620 cgaatctaca cgacaggccc gcagacgcgg ctaacacaca cgccggcaac ccagacccca 100680 gtgggttggt tgcgcggtcc cgtctcctgg ctagttcttt cccccaccac caaataatca 100740 gacgacaacc gcaggttttt gtaatgtatg tgctcgtgtt tattgtggat acgaaccggg 100800 gacgggaggg gaaaacccag acgggggatg cgggtccggt cgcgccccct acccaccgta 100860 ctcgtcaatt ccaagggcat cggtaaacat ctgctcaaac tcgaagtcgg ccatatccag 100920 agcgccgtag ggggcggagt cgtggggggt aaatcccgga cccggggaat ccccgtcccc 100980 caacatgtcc agatcgaaat cgtctagcgc gtcggcatgc gccatcgcca cgtcctcgcc 101040 gtctaagtgg agctcgtccc ccaggctgac atcggtcggg ggggccgtcg acagtctgcg 101100 cgtgtgtccc gcggggagaa aggacaggcg cggagccgcc agccccgcct cttcgggggc 101160 gtcgtcgtcc gggagatcga gcaggccctc gatggtagac ccgtaattgt ttttcgtacg 101220 cgcgcggctg tacgcgtgtt cccgcatgac cgcctcggag ggcgaggtcg tgaagctgga 101280 atacgagtcc aacttcgccc gaatcaacac cataaagtac ccagaggcgc gggcctggtt 101340 gccatgcagg gtgggagggg tcgtcaacgg cgcccctggc tcctccgtag ccgcgctgcg 101400 caccagcggg aggttaaggt gctcgcgaat gtggtttagc tcccgcagcc ggcgggcctc 101460 gattggcact ccccggacgg tgagcgctcc gttgacgaac atgaagggct ggaacagacc 101520 cgccaactga cgccagctct ccaggtcgca acagaggcag tcaaacaggt cgggccgcat 101580 catctgctcg gcgtacgcgg cccataggat ctcgcgggtc aaaaatagat acaaatgcaa 101640 aaacagaaca cgcgccagac gagcggtctc tcggtagtac ctgtccgcga tcgtggcgcg 101700 cagcatttct cccaggtcgc gatcgcgtcc gcgcatgtgc gcctggcggt gcagctgccg 101760 gacgctggcg cgcaggtacc ggtacagggc cgagcagaag ttggccaaca cggttcgata 101820 gctctcctcc cgcgcccgta gctcggcgtg gaagaaacga gagagcgctt cgtagtagag 101880 cccgaggccg tcgcgggtgg ccggaagcgt cgggaaggcc acgtcgccgt gggcgcgaat 101940 gtcgatttgg gcgcgttcgg ggacgtacgc gtccccccat tccaccacat cgctgggcag 102000 cgttgatagg aatttacact cccggtacag gtcggcgttg gtcggtaacg ccgaaaacaa 102060 atcctcgttc caggtatcga gcatggtaca tagcgcgggg cccgcgctaa agcccaagtc 102120 gtcgaggaga cggttaaaga gggcggcggg ggggacgggc atgggcgggg agggcatgag 102180 ctgggcctgg ctcaggcgcc ccgttgcgta cagcggaggg gccgccgggg tgtttttggg 102240 acccccggcc gggcgggggg gtggtggcga agcgccgtcc gcgtccatgt cggcaaacag 102300 ctcgtcgacc aagaggtcca ttgggtgggg ttgatacggg aaagacgata tcgggctttt 102360 gatgcgatcg tccccgcccg cccagagagt gtgggacgcc cgacggcgcg ggaagagaaa 102420 aacccccaaa cgcgttagag gaccggacgg accttatggg gggaagtggg cagcgggaac 102480 cccgtccgtt cccgaggaat gacagcccgt ggtcgccacc ccgcatttaa gcaacccgca 102540 cgggccgccc cgtacctcgt gacttccccc cacattggct cctgtcacgt gaaggcaaac 102600 cgagggcggc tgtccaaccc accccccgcc acccagtcac ggtccccgtc ggattgggaa 102660 acaaaggcac gcaacgccaa caccgaatga acccctgttg gtgctttatt gtctgggtac 102720 ggaagttttt cactcgacgg gccgtctggg gcgagaagcg gagcgggctg gggctcgagg 102780 tcgctcggtg gggcgcgacg ccgcagaacg ccctcgagtc gccgtggccg cgtcgacgtc 102840 ctgcaccacg tctggattca ccaactcgtt ggcgcgctga atcaggtttt tgccctcgca 102900 gaccgtcacg cggatggtgg tgatgccaag gagttcgttg aggtcttcgt ctgtgcgcgg 102960 acgcgacatg tcccagagct ggaccgccgc catccgggca tgcatggccg ccaggcgccc 103020 aaccgcggcg cagaagacgc gcttgttaaa gccggccacc cggggggtcc atggcgcgtc 103080 ggggtttggg ggggcggtgc taaagtgcag ctttctggcc agcccctgcg cgggtgtctt 103140 ggatcgggtt ggcgccgtcg acgcgggggc gtctgggagt gcggcggatt ctggctgggc 103200 cgatttcctg ccgcgggtgg tctccgccgc cggggccgcg ggggccttag tcgccacccg 103260 ctgggttcgg ggggcccggg gggcggtggt gggtgtgcgt ccggcccctc cggacccagc 103320 gggcggcgga ggcgcccgcg caggccccgg ggcggacaaa accgccccgg aaacgggacg 103380 ccgcgtccgg gggacctccg ggtgttcgtc gtcttcggat gacgagcccc cgtagagggc 103440 ataatccgac tcgtcgtact ggacgaaacg gacctcgccc cttgggcgcg cgcgtgtctg 103500 tagggcgcca cggcgggagg tgtcaggcgg actatcggga ctcgccatac atgaagacgg 103560 ggtgtagtac agatcctcgt actcatcgcg cggaacctcc cgcggacccg acttcacgga 103620 gcggcgagag gtcatggttc cacgaacacg ctagggtcgg atgcgcggac aattaggcct 103680 gggttcggac ggcgggggtg gtgcaggtgt ggagaggtcg agcgataggg gcggcccggg 103740 agagaagaga gggtccgcaa aacccactgg ggatgcgtga gtggccctct gtgggcggtg 103800 ggggagagtc ttataggaag tgcatataac cacaacccat gggtctaacc aatccccagg 103860 ggccaagaaa cagacacgcc ccaaacggtc tcggtttccg cgaggaaggg gaagtcctgg 103920 gacaccctcc acccccaccc ctcaccccac acagggcggg ttcaggcgtg cccggcagcc 103980 agtagcctct ggcagatctg acagacgtgt gcgataatac acacgcccat cgaggccatg 104040 cctacataaa agggcaccag ggcccccggg gcagacattt ggccagcgtt ttgggtctcg 104100 caccgcgcgc ccccgatccc atcgcgcccg ccctcctcgc cgggcggctc cccgtgcggg 104160 cccgcgtctc ccgccgctaa ggcgacgagc aagacaaaca acaggcccgc ccgacagacc 104220 cttctggggg ggcccatcgt ccctaacagg aagatgagtc agtggggatc cggggcgatc 104280 cttgtccagc cggacagctt gggtcggggg tacgatggcg actggcacac ggccgtcgct 104340 actcgcgggg gcggagtcgt gcaactgaac ctggtcaaca ggcgcgcggt ggcttttatg 104400 ccgaaggtca gcggggactc cggatgggcc gtcgggcgcg tctctctgga cctgcgaatg 104460 gctatgccgg ctgacttttg tgcgattatt cacgcccccg cgctatccag cccagggcac 104520 cacgtaatac tgggtcttat cgactcgggg taccgcggaa ccgttatggc cgtggtcgta 104580 gcgcctaaaa ggacgcggga atttgccccc gggaccctgc gggtcgacgt gacgttcctg 104640 gacatcctgg cgaccccccc ggccctcacc gagccgattt ccctgcggca gttcccgcaa 104700 ctggcgcccc cccctccaac cggggccggg atacgcgcag atccttggtt ggagggggcg 104760 ctcggggacc caagcgtgac tcctgcccta ccggcgcgac gccgagggcg gtccctcgtc 104820 tatgccggcg agctgacgcc ggttcagacg gaacacgggg acggcgtacg agaagccatc 104880 gccttccttc caaaacgcga ggaggatgcc ggtttcgaca ttgtcgtccg tcgcccggtc 104940 accgtcccgg caaacggcac cacggtcgtg cagccatccc tccgcatgct ccacgcggac 105000 gccgggcccg cggcctgcta tgtgctgggg cggtcgtcgc tcaacgcccg cggcctcctg 105060 gtcgttccta cgcgctggct ccccgggcac gtatgtgcgt ttgttgttta caaccttacg 105120 ggggttcctg tgaccctcga ggccggcgcc aaggtcgccc agctcctggt tgcgggggcg 105180 gacgctcttc cttggatccc cccggacaac tttcacggga ccaaagcgct tcgaaactac 105240 cccaggggtg ttccggactc aaccgccgaa cccaggaacc cgccgctcct ggtgtttacg 105300 aacgagtttg acgcggaggc ccccccgagc gagcgcggga ccgggggttt tggctctacc 105360 ggtatttagc ccatagcttg gggttcgttc cgggcaataa aaaacgtttg tatctcatct 105420 ttcctgtgtg tagttgtttc tgttggatgc ctgtgggtct atcacacccg cccctccatc 105480 ccacaaacac agaacacacg ggttggatga aaacacgcat ttattgaccc aaaacacacg 105540 gagctgctcg agatgggcca gggcgaggtg cggttgggga ggctgtaggt ctgggaacgg 105600 acacgcgggg acacgattcc ggtttggggt ccgggagggc gtcgccgttt cgggcggcag 105660 gcgccagcgt aacctccggg ggcggcgtgt gggggtgccc caaggagggc gcctcggtca 105720 ccccaagccc ccccgagcgg gttcccccgg caaccccgaa ggcggagagg ccaagggccc 105780 gttcggcgat ggccacatcc tccatgacca cgtcgctctc ggccatgctc cgaatagcct 105840 gggagacgag cacatccgcg gacttgtcag ccgcccccac ggacatgtac atctgcagga 105900 tggtggccat acacgtgtcc gccaggcgcc gcatcttgtc ctgatgggcc gccacggccc 105960 cgtcgatcgt gggggcctcg agcccggggt ggtggcgcgc cagtcgttct aggttcacca 106020 tgcaggcgtg gtacgtgcgg gccaaggcgc gggccttcac gaggcgtcgg gtgtcgtcca 106080 gggaccccag ggcgtcatcg agcgtgatgg gggcgggaag tagcgcgtta acgaccacca 106140 gggcctcctg cagccgcggc tccgcctccg agggcggaac ggccgcgcgg atcatctcat 106200 attgttcctc ggggcgcgct ccccagccac atatagcccc gagaagagaa gccatcgcgg 106260 gcgggtactg gcccttgggc gcgcggacgc aatggggcag gaagacggga accgcgggga 106320 gaggcgggcg gccgggactc ccgtggaggt gaccgcgctt tatgcgaccg acgggtgcgt 106380 tattacctct tcgatcgccc tcctcacaaa ctctctactg ggggccgagc cggtttatat 106440 attcagctac gacgcataca cgcacgatgg ccgtgccgac gggcccacgg agcaagacag 106500 gttcgaagag agtcgggcgc tctaccaagc gtcgggcggg ctaaatggcg actccttccg 106560 agtaaccttt tgtttattgg ggacggaagt gggtgggacc caccaggccc gcgggcgaac 106620 ccgacccatg ttcgtctgtc gcttcgagcg agcggacgac gtcgccgcgc tacaggacgc 106680 cctggcgcac gggaccccgc tacaaccgga ccacatcgcc gccaccctgg acgcggaggc 106740 cacgttcgcg ctgcatgcga acatgatcct ggctctcacc gtggccgtca acaacgccag 106800 cccccgcacc ggacgcgacg ccgccgcggc gcagtatgat cagggcgcgt ccctacgctc 106860 gctcgtgggg cgcacgtccc tgggacaacg cggccttacc acgctatacg tccaccacga 106920 ggcgcgcgtg ctggccgcgt accgcagggc gtattatgga agcgcgcaga gtcccttctg 106980 gtttcttagc aaattcgggc ctgacgaaaa aagcctggtg ctcaccactc ggtactacct 107040 gcttcaggcc cagcgtctgg ggggcgcggg ggccacgtac gacctgcagg ccatcaagga 107100 catctgcgcc acctacgcga ttccccacgc cccccgcccc gacaccgtca gcgccgcgtc 107160 cctgacctcg tttgccgcca tcacgcggtt ctgttgcacg agccagtacg cccgcggggc 107220 cgcggcggcc gggtttccgc tttacgtgga gcgccgtatt gcggccgacg tccgcgagac 107280 cagtgcgctg gagaagttca taacccacga tcgcagttgc ctgcgcgtgt ccgaccgtga 107340 attcattacg tacatttacc tggcccattt tgagtgtttc agccccccgc gcctagccac 107400 gcatcttcgg gccgtgacga cccaggaccc caaccccgcg gccaacacgg agcagccctc 107460 gcccctgggc agggaggccg tggaacaatt tttttgccac gtgcgcgccc aactgaatat 107520 cggggagtac gtcaaacaca acgtgacccc ccgggagacc gtcctggatg gcgatacggc 107580 caaggcctac ctgcgcgctc gcacgtacgc gcccggggcc ctgacgcccg cccccgcgta 107640 ttgcggggcc gtggactccg ccaccaaaat gatggggcgt ttggcggacg ccgaaaagct 107700 cctggtcccc cgcgggtggc ccgcgtttgc gcccgccagt cccggggagg atacggcggg 107760 cggcacgccg cccccacaga cctgcggaat cgtcaagcgc ctcctgagac tggccgccac 107820 ggaacaacag gacaccacgc ccccggcgat cgcggcgctt atccgtaatg cggcggtgca 107880 gactcccctg cccgtctacc ggatatccat ggtccccacg ggacaggcat ttgccgcgct 107940 ggcctgggac gactgggccc gcataacgcg ggacgctcgc ctggccgaag cggtcgtgtc 108000 cgccgaagcg gcggcgcacc ccgaccacgg cgcgctgggc aggcggctca cggatcgcat 108060 ccgcgcccag ggccccgtga tgccccctgg cggcctggat gccggggggc agatgtacgt 108120 gaatcgcaac gagatattta acggcgcgct ggcaatcaca aacatcatcc tggatctcga 108180 catcgccctg aaggagcccg tcccctttcg ccggctccac gaggccctgg gccactttag 108240 gcgcggggct ctggcggcgg ttcagctcct gtttcccgcg gcccgcgtgg accccgacgc 108300 atatccctgt tattttttca aaagcgcatg tcggcccggc ccggcgtccg tgggttccgg 108360 cagcggactc ggcaacgacg acgacgggga ctggtttccc tgctacgacg acgccggtga 108420 tgaggagtgg gcggaggacc cgggcgccat ggacacatcc cacgatcccc cggacgacga 108480 ggttgcctac tttgacctgt gccacgaagt cggccccacg gcggaacctc gcgaaacgga 108540 ttcgcccgtg tgttcctgca ccgacaagat cggactgcgg gtgtgcatgc ccgtccccgc 108600 cccgtacgtc gtccacggtt ctctaacgat gcggggggtg gcacgggtca tccagcaggc 108660 ggtgctgttg gaccgagatt ttgtggaggc catcgggagc tacgtaaaaa acttcctgtt 108720 gatcgatacg ggggtgtacg cccacggcca cagcctgcgt ttgccgtatt ttgccaaaat 108780 cgcccccgac gggcctgcgt gcggaaggct gctgccagtg tttgtgatcc cccccgcctg 108840 caaagacgtt ccggcgtttg tcgccgcgca cgccgacccg cggcgcttcc attttcacgc 108900 cccgcccacc tatctcgctt ccccccggga gatccgtgtc ctgcacagcc tgggtgggga 108960 ctatgtgagc ttctttgaaa ggaaggcgtc ccgcaacgcg ctggaacact ttgggcgacg 109020 cgagaccctg acggaggtcc tgggtcggta caacgtacag ccggatgcgg gggggaccgt 109080 cgaggggttc gcatcggaac tgctggggcg gatagtcgcg tgcatcgaaa cccactttcc 109140 cgaacacgcc ggcgaatatc aggccgtatc cgtccggcgg gccgtcagta aggacgactg 109200 ggtcctccta cagctagtcc ccgttcgcgg taccctgcag caaagcctgt cgtgtctgcg 109260 ctttaagcac ggccgggcga gtcgcgccac ggcgcggaca ttcgtcgcgc tgagcgtcgg 109320 ggccaacaac cgcctgtgcg tgtccttgtg tcagcagtgc tttgccgcca aatgcgacag 109380 caaccgcctg cacacgctgt ttaccattga cgccggcacg ccatgctcgc cgtccgttcc 109440 ctgcagcacc tctcaaccgt cgtcttgata acggcgtacg gcctcgtgct cgtgtggtac 109500 accgtcttcg gtgccagtcc gctgcaccga tgtatttacg cggtacgccc caccggcacc 109560 aacaacgaca ccgccctcgt gtggatgaaa atgaaccaga ccctattgtt tctgggggcc 109620 ccgacgcacc cccccaacgg gggctggcgc aaccacgccc atatctgcta cgccaatctt 109680 atcgcgggta gggtcgtgcc cttccaggtc ccacccgacg ccacgaatcg tcggatcatg 109740 aacgtccacg aggcagttaa ctgtctggag accctatggt acacacgggt gcgtctggtg 109800 gtcgtagggt ggttcctgta tctggcgttc gtcgccctcc accaacgccg atgtatgttt 109860 ggtgtcgtga gtcccgccca caagatggtg gccccggcca cctacctctt gaactacgca 109920 ggccgcatcg tatcgagcgt gttcctgcag tacccctaca cgaaaattac ccgcctgctc 109980 tgcgagctgt cggtccagcg gcaaaacctg gttcagttgt ttgagacgga cccggtcacc 110040 ttcttgtacc accgccccgc catcggggtc atcgtaggct gcgagttgat gctacgcttt 110100 gtggccgtgg gtctcatcgt cggcaccgct ttcatatccc ggggggcatg tgcgatcaca 110160 taccccctgt ttctgaccat caccacctgg tgttttgtct ccaccatcgg cctgacagag 110220 ctgtattgta ttctgcggcg gggcccggcc cccaagaacg cagacaaggc cgccgccccg 110280 gggcgatcca aggggctgtc gggcgtctgc gggcgctgtt gttccatcat cctgtcgggc 110340 atcgcaatgc gattgtgtta tatcgccgtg gtggccgggg tggtgctcgt ggcgcttcac 110400 tacgagcagg agatccagag gcgcctgttt gatgtatgac gtcacatcca ggccggcgga 110460 aaccggaacg gcatatgcaa actggaaact gtcctgtctt ggggcccacc cacccgacgc 110520 gtcatatgta aatgaaaatc gttcccccga ggccatgtgt agcctggatc ccaacgaccc 110580 cgcccatggg tcccaattgg ccgtcccgtt accaagacca acccagccag cgtatccacc 110640 cccgcccggg tccccgcgga agcggaacgg tgtatgtgat atgctaatta aatacatgcc 110700 acgtacttat ggtgtctgat tggtccttgt ctgtgccgga ggtggggcgg gggccccgcc 110760 cggggggcgg aactaggagg ggtttgggag agccggcccc ggcaccacgg gtataaggac 110820 atccaccacc cggccggtgg tggtgtgcag ccgtgttcca accacggtca cgcttcggtg 110880 cctctccccg attcgggccc ggtcgcttgc taccggtgcg ccaccaccag aggccatatc 110940 cgacacccca gccccgacgg cagccgacag cccggtcatg gcgactgaca ttgatatgct 111000 aattgacctc ggcctggacc tctccgacag cgatctggac gaggaccccc ccgagccggc 111060 ggagagccgc cgcgacgacc tggaatcgga cagcaacggg gagtgttcct cgtcggacga 111120 ggacatggaa gacccccacg gagaggacgg accggagccg atactcgacg ccgctcgccc 111180 ggcggtccgc ccgtctcgtc cagaagaccc cggcgtaccc agcacccaga cgcctcgtcc 111240 gacggagcgg cagggcccca acgatcctca accagcgccc cacagtgtgt ggtcgcgcct 111300 cggggcccgg cgaccgtctt gctcccccga gcggcacggg ggcaaggtgg cccgcctcca 111360 acccccaccg accaaagccc agcctgcccg cggcggacgc cgtgggcgtc gcaggggtcg 111420 gggtcgcggt ggtcccgggg ccgccgatgg tttgtcggac ccccgccggc gtgcccccag 111480 aaccaatcgc aacccggggg gaccccgccc cggggcgggg tggacggacg gccccggcgc 111540 cccccatggc gaggcgtggc gcggaagtga gcagcccgac ccacccggag gcccgcggac 111600 acggagcgtg cgccaagcac cccccccgct aatgacgctg gcgattgccc ccccgcccgc 111660 ggacccccgc gccccggccc cggagcgaaa ggcgcccgcc gccgacacca tcgacgccac 111720 cacgcggttg gtcctgcgct ccatctccga gcgcgcggcg gtcgaccgca tcagcgagag 111780 cttcggccgc agcgcacagg tcatgcacga cccctttggg gggcagccgt ttcccgccgc 111840 gaatagcccc tgggccccgg tgctggcggg ccaaggaggg ccctttgacg ccgagaccag 111900 acgggtctcc tgggaaacct tggtcgccca cggcccgagc ctctatcgca cttttgccgg 111960 caatcctcgg gccgcatcga ccgccaaggc catgcgcgac tgcgtgctgc gccaagaaaa 112020 tttcatcgag gcgctggcct ccgccgacga gacgctggcg tggtgcaaga tgtgcatcca 112080 ccacaacctg ccgctgcgcc cccaggaccc cattatcggg acggccgcgg cggtgctgga 112140 taacctcgcc acgcgcctgc ggccctttct ccagtgctac ctgaaggcgc gaggcctgtg 112200 cggcctggac gaactgtgtt cgcggcggcg tctggcggac attaaggaca ttgcatcctt 112260 cgtgtttgtc attctggcca ggctcgccaa ccgcgtcgag cgtggcgtcg cggagatcga 112320 ctacgcgacc cttggtgtcg gggtcggaga gaagatgcat ttctacctcc ccggggcctg 112380 catggcgggc ctgatcgaaa tcctagacac gcaccgccag gagtgttcga gtcgtgtctg 112440 cgagttgacg gccagtcaca tcgtcgcccc cccgtacgtg cacggcaaat atttttattg 112500 caactccctg ttttaggtac aataaaaaca aaacatttca aacaaatcgc cccacgtgtt 112560 gtccttcttt gctcatggcc ggcggggcgt gggtcacggc agatggcggg ggtgggcccg 112620 gcgtacggcc tgggtgggcg gagggaacta acccaacgta taaatccgtc cccgctccaa 112680 ggccggtgtc atagtgccct taggagcttc ccgcccgggc gcatcccccc ttttgcacta 112740 tgacagcgac ccccctcacc aacctgttct tacgggcccc ggacataacc cacgtggccc 112800 ccccttactg cctcaacgcc acctggcagg ccgaaacggc catgcacacc agcaaaacgg 112860 actccgcttg cgtggccgtg cggagttacc tggtccgcgc ctcctgtgag accagcggca 112920 caatccactg ctttttcttt gcggtataca aggacaccca ccatacccct ccgctgatta 112980 ccgagctccg caactttgcg gacctggtta accacccgcc ggtcctacgc gaactggagg 113040 ataagcgcgg ggtgcggctg cggtgtgcgc ggccgtttag cgtcgggacg attaaggacg 113100 tctctgggtc cggcgcgtcc tcggcgggag agtacacgat aaacgggatc gtgtaccact 113160 gccactgtcg gtatccgttc tcaaaaacat gctggatggg ggcctccgcg gccctacagc 113220 acctgcgctc catcagctcc agcggcatgg ccgcccgcgc ggcagagcat cgacgcgtca 113280 agattaaaat taaggcgtga tctccaaccc cccatgaatg tgtgtaaccc cccccaaaaa 113340 aataaagagc cgtaacccaa ccaaaccagg cgtggtgtga gtttgtggac ccaaagccct 113400 cagagacaat gcgacaggcc agtatggacc gtgatacttt tatttattaa ctcacagggg 113460 cgcttaccgc cacaggaata ccagaataat gaccaccaca atcgcgacca ccccaaatac 113520 agatccgtgt cggcagccgc gctccgtgtg gacgatcggg gcgtcctcgg gctcatatag 113580 tcccaggggc cggcgggaag gaggagcagc ggaggccgcc ggccccccgc cccccggcgg 113640 gcccaccccg aacggaattc cattatgcac gaccccgccc cgacgccggc acgccggggg 113700 cccgtggccg cggcccgttg gtcgaacccc cggccccgcc catccgcgcc atctgccatg 113760 gacggggcgc gagggcgggt gggtccgcgc cccgccccgc atggcatctc attaccgccc 113820 gatccggcgg tttccgcttc cgttccgcat gctaacgagg aacgggcagg gggcggggcc 113880 cgggccccga cttcccggtt cggcggtaat gagatacgag ccccgcgcgc ccgttggccg 113940 tccccgggcc cccggtcccg cccgccggac gccgggacca acgggacggc gggcggccct 114000 tgggccgccc gccttgccgc ccccccattg gccggcgggc gggaccgccc caagggggcg 114060 gggccgccgg gtaaaagaag tgagaacgcg aagcgttcgc acttcgtccc aatatatata 114120 tattattagg gcgaagtgcg agcactggcg ccgtgcccga ctccgcgccg gccccggggg 114180 cggacccggg cggcgggggg cgggtctctc cggcgcacat aaaggcccgg cgcgaccgac 114240 gcccgcagac ggcgccagcc acgaacgacg ggagcggctg cggagcacgc ggaccgggag 114300 cgggagtcgc agagggccgt cggagcggac ggcgtcggca tcgcgacgcc ccggctcggg 114360 atcgggatcg catcggaaag ggacacgcgg acgcgggggg gaaagacccg cccaccccac 114420 ccacgaaaca caggggacgc accccggggg cctccgacga cagaaaccca ccggtccgcc 114480 ttttttgcac gggtaagcac cttgggtggg cagaggaggg gggacgcggg ggcggaggag 114540 gggggacgcg ggggcggagg aggggggacg cgggggcgga ggagggggga cgcgggggcg 114600 gaggaggggg gacgcggggg cggaggaggg ggctcacccg cgttcgtgcc ttcccgcagg 114660 aggaacgccc tcgtcgaggc gaccggcggc gaccgttgcg tggaccgctt cctgctcgtc 114720 gggggggggg gagccactgt ggtcctccgg gacgttttct ggatggccga catttcccca 114780 ggcgcttttg tgccttgtgt aaaagcgcgg cgtcccgctc tccgatcccc gcccctgggc 114840 acgcgcaagc gcaagcgccc tgcccgcccc ctctcatcgg agtctgaggt cgaatccgag 114900 acagccttgg agtctgaggt cgaatccgag acagcatcgg attcgaccga gtctggggac 114960 caggaggaag ccccccgcat cggtggccgt agggcccccc ggaggcttgg ggggcggttt 115020 tttctggaca tgtcggcgga atccaccacg gggacggaaa cggatgcgtc ggtgtcggac 115080 gaccccgacg acacgtccga ctggtcttgt gacgacattc ccccacgacc caagcgggcc 115140 cgggtaaacc tgcggctcac tagctctccc gatcggcggg atggggttat ttttcctaag 115200 atggggcggg tccggtctac ccgggaaacg cagccccggg cccccacccc gtcggcccca 115260 agcccaaatg caatgctccg gcgctcggtg cgccaggccc agaggcggag cagcgcacga 115320 tggacccccg acctgggcta catgcgccag tgtatcaatc agctgtttcg ggtcctgcgg 115380 gtcgcccggg acccccacgg cagtgccaac cgcctgcgcc acctgatacg cgactgttac 115440 ctgatgggat actgccgagc ccgtctggcc ccgcgcacgt ggtgccgctt gctgcaggtg 115500 tccggcggaa cctggggcat gcacctgcgc aacaccatac gggaggtgga ggctcgattc 115560 gacgccaccg cagaacccgt gtgcaagctt ccttgtttgg aggccagacg gtacggcccg 115620 gagtgtgatc ttagtaatct cgagattcat ctcagcgcga caagcgatga tgaaatctcc 115680 gatgccaccg atctggaggc cgccggttcg gaccacacgc tcgcgtccca gtccgacacg 115740 gaggatgccc cctcccccgt tacgctggaa accccagaac cccgcgggtc cctcgctgtg 115800 cgtctggagg atgagtttgg ggagtttgac tggacccccc aggagggctc ccagccctgg 115860 ctgtctgcgg tcgtggccga taccagctcc gtggaacgcc cgggcccatc cgattctggg 115920 gcgggtcgcg cagcagaaga ccgcaagtgt ctggacggct gccggaaaat gcgcttctcc 115980 accgcctgcc cctatccgtg cagcgacacg tttctccggc cgtgagtccg gtcgccccga 116040 cccccttgta tgtccccaaa ataaaagacc aaaatcaaag cgtttgtccc agcgtcttaa 116100 tggcgggaag ggcggagaga aacagaccac gcgtacatgg ggggtgtttg ggggtttatt 116160 gacatcgggg ctacagggtg gtaaccggat agcagatgtg aggaagtctg ggccgttcgc 116220 cgcgaacggc gatcagaggg tccgtttctt gcggaccacg gcccggtgat gtgggttgct 116280 cgtctaaaat ctcgggcata cccatacacg cacaacacgg acgccgcacc gaatgggacg 116340 tcgtaagggg gtgggaggta gctgggtggg gtttgtgcag agcaatcagg gaccgcagcc 116400 agcgcataca atcgcgctcc cgtccgttgg tcccgggcag gaccacgccg tactggtatt 116460 cgtaccggct gagcagggtc tccagggggt ggttgggtgc cgcggggaac ggggtccacg 116520 ccacggtcca ctcgggcaaa aaccgagtcg gcacggccca cggttctccc acccacgcgt 116580 ctggggtctt gatggcgata aatcttaccc cgagccggat tttttgggcg tattcgagaa 116640 acggcacaca cagatccgcc gcgcctacca cccacaagtg gtagaggcga ggggggctgg 116700 gttggtctcg gtgcaacagt cggaagcacg ccacggcgtc cacgacctcg gtgctctcca 116760 aggggctgtc ctccgcaaac aggcccgtgg tggtgtttgg ggggcagcga caggacctag 116820 tgcgcacgat cgggcgggtg ggtttgggta agtccatcag cggctcggcc aaccgtcgaa 116880 ggttggccgg gcgaacgacg accggggtac ccaggggttc tgatgccaaa atgcggcact 116940 gcctaagcag gaagctccac agggccgggc ttgcgtcgac ggaagtccgg ggcagggcgt 117000 tgttctggtc aaggagggtc attacgttga cgacaacaac gcccatgttg gtatattaca 117060 ggcccgtgtc cggtttgggg cacttgcaga tttgtaaggc cacgcacggc ggggagacag 117120 gccgacgcgg gggctgctct aaaaatttaa gggccctacg gtccacagac ccgccttccc 117180 gggggggccc ttggagcgac cggcagcgga ggcgtccggg ggaggggagg gttatttacg 117240 ggggggtagg tcagggggtg ggtcgtcaaa ctgccgctcc ttaaaacccc ggggcccgtc 117300 gttcggggtg ctcgttggtt ggcactcacg gtgcggcgaa tggcctgtcg taagttttgt 117360 cgcgtttacg ggggacaggg caggaggaag gaggaggccg tcccgccgga gacaaagccg 117420 tcccgggtgt ttcctcatgg ccccttttat accccagccg aggacgcgtg cctggactcc 117480 ccgcccccgg agacccccaa accttcccac accacaccac ccggcgatgc cgagcgcctg 117540 tgtcatctgc aggagatcct ggcccagatg tacggaaacc aggactaccc catagaggac 117600 gaccccagcg cggatgccgc ggacgatgtc gacgaggacg ccccggacga cgtggcctat 117660 ccggaggaat acgcagagga gctttttctg cccggggacg cgaccggtcc ccttatcggg 117720 gccaacgacc acatccctcc cccgcgtggc gcatctcccc ccggtatacg acgacgcagc 117780 cgggatgaga ttggggccac gggatttacc gcagaagagc tggacgccat ggacaggcag 117840 gcggctcgag ccatcagccg cggcggcaag cccccctcga ccatggccaa gctggtgact 117900 ggcatgggct ttacgatcca cggagcgctc accccaggat cggaggggtg tgtctttgac 117960 agcagccacc cagattaccc ccaacgggta atcgtgaagg cggggtggta cacgagcacg 118020 agccacgagg cgcgactgct gaggcgactg gaccacccgg cgatcctgcc cctcctggac 118080 ctgcatgtcg tctccggggt cacgtgtctg gtcctcccca agtaccaggc cgacctgtat 118140 acctatctga gtaggcgcct gaacccactg ggacgcccgc agatcgcagc ggtctcccgg 118200 cagctcctaa gcgccgttga ctacattcac cgccagggca ttatccaccg cgacattaag 118260 accgaaaata tttttattaa cacccccgag gacatttgcc tgggggactt tggtgccgcg 118320 tgcttcgtgc agggttcccg atcaagcccc ttcccctacg gaatcgccgg aaccatcgac 118380 accaacgccc ccgaggtcct ggccggggat ccgtatacca cgaccgtcga catttggagc 118440 gccggtctgg tgatcttcga gactgccgtc cacaacgcgt ccttgttctc ggccccccgc 118500 ggccccaaaa ggggcccgtg cgacagtcag atcacccgca tcatccgaca ggcccaggtc 118560 cacgttgacg agttttcccc gcatccagaa tcgcgcctca cctcgcgcta ccgctcccgc 118620 gcggccggga acaatcgccc gccttacacc cgaccggcct ggacccgcta ctacaagatg 118680 gacatagacg tcgaatatct ggtttgcaaa gccctcacct tcgacggcgc gcttcgcccc 118740 agcgccgcag agctgctttg tttgccgctg tttcaacaga aatgaccgcc cccggggggc 118800 ggtgctgttt gcgggttggc acaaaaagac cccgacccgc gtctgtggtg tttttggcat 118860 catgtcgccg ggcgccatgc gtgccgttgt tcccattatc ccattccttt tggttcttgt 118920 cggtgtatcg ggggttccca ccaacgtctc ctccaccacc caaccccaac tccagaccac 118980 cggtcgtccc tcgcatgaag cccccaacat gacccagacc ggcaccaccg actctcccac 119040 cgccatcagc cttaccacgc ccgaccacac accccccatg ccaagtatcg gactggagga 119100 ggaggaggaa gaggaggagg gggccgggga tggcgaacat cttaaggggg gagatgggac 119160 ccgtgacacc ctaccccagt ccccgggtcc agccgtcccg ttggccgggg atgacgagaa 119220 ggacaaaccc aaccgtcccg tagtcccacc ccccggtccc aacaactccc ccgcgcgccc 119280 cgagaccagt cgaccgaaga caccccccac cagtatcggg ccgctggcaa ctcgacccac 119340 gacccaactc ccctcaaagg ggcgaccctt ggttccgacg cctcaacata ccccgctgtt 119400 ctcgttcctc actgcctccc ccgccctgga caccctcttc gtcgtcagca ccgtcatcca 119460 caccttatcg tttgtgtgta ttgttgctat ggcgacacac ctgtgtggtg gttggtccag 119520 acgcgggcga cgcacacacc ctagcgtgcg ttacgtgtgc ctgccgcccg aacgcgggta 119580 gggtatgggg cggggatggg gagagcccac acgcggaaag caagaacaat aaaggcggcg 119640 ggatctagtt gatatgcgtc tctgggtgtt tttggggtgt ggtgggcgcg gggcggtcat 119700 tggacggggg tgcagttaaa tacatgcccg ggacccatga agcatgcgcg acttccgggc 119760 ctcggaaccc acccgaaacg gccaacggac gtctgagcca ggcctggcta tccggagaaa 119820 cagcacacga cttggcgttc tgtgtgtcgc gatgtctctg cgcgcagtct ggcatctggg 119880 gcttttggga agcctcgtgg gggctgttct tgccgccacc catctgggac ctgcggccaa 119940 cacaacggac cccttaacgc acgccccagt gtcccctcac cccagccccc tggggggctt 120000 tgccgtcccc ctcgtagtcg gtgggctgtg tgccgtagtc ctgggggcgg cgtgtctgct 120060 tgagctcctg cgtcgtacgt gccgcgggtg ggggcgttac catccctaca tggacccagt 120120 tgtcgtataa ttttttcccc cccccccttc tccgcatggg tgatgtcggg tccaaactcc 120180 cgacaccacc agctggcatg gtataaatca ccggtgcgcc ccccaaacca tgtccggcag 120240 ggggatgggg ggcgaatgcg gagggcaccc aacaacaccg ggctaaccag gaaatccgtg 120300 gccccggccc ccaacaaaga tcgcggtagc ccggccgtgt gacattatcg tccataccga 120360 ccacaccgac gaatccccta agggggaggg gccattttac gaggaggagg ggtataacaa 120420 agtctgtctt taaaaagcag gggttaggga gttgttcggt cataagcttc agtgcgaacg 120480 accaactacc ccgatcatca gttatcctta aggtctcttt tgtgtggtgc gttccggtat 120540 ggggggggct gccgccaggt tgggggccgt gattttgttt gtcgtcatag tgggcctcca 120600 tggggtccgc ggcaaatatg ccttggcgga tgcctctctc aagatggccg accccaatcg 120660 ctttcgcggc aaagaccttc cggtcctgga ccagctgacc gaccctccgg gggtccggcg 120720 cgtgtaccac atccaggcgg gcctaccgga cccgttccag ccccccagcc tcccgatcac 120780 ggtttactac gccgtgttgg agcgcgcctg ccgcagcgtg ctcctaaacg caccgtcgga 120840 ggccccccag attgtccgcg gggcctccga agacgtccgg aaacaaccct acaacctgac 120900 catcgcttgg tttcggatgg gaggcaactg tgctatcccc atcacggtca tggagtacac 120960 cgaatgctcc tacaacaagt ctctgggggc ctgtcccatc cgaacgcagc cccgctggaa 121020 ctactatgac agcttcagcg ccgtcagcga ggataacctg gggttcctga tgcacgcccc 121080 cgcgtttgag accgccggca cgtacctgcg gctcgtgaag ataaacgact ggacggagat 121140 tacacagttt atcctggagc accgagccaa gggctcctgt aagtacgccc tcccgctgcg 121200 catccccccg tcagcctgcc tctcccccca ggcctaccag cagggggtga cggtggacag 121260 catcgggatg ctgccccgct tcatccccga gaaccagcgc accgtcgccg tatacagctt 121320 gaagatcgcc gggtggcacg ggcccaaggc cccatacacg agcaccctgc tgcccccgga 121380 gctgtccgag acccccaacg ccacgcagcc agaactcgcc ccggaagacc ccgaggattc 121440 ggccctcttg gaggaccccg tggggacggt ggcgccgcaa atcccaccaa actggcacat 121500 cccgtcgatc caggacgccg cgacgcctta ccatcccccg gccaccccga acaacatggg 121560 cctgatcgcc ggcgcggtgg gcggcagtct cctggcagcc ctggtcattt gcggaattgt 121620 gtactggatg caccgccgca ctcggaaagc cccaaagcgc atacgcctcc cccacatccg 121680 ggaagacgac cagccgtcct cgcaccagcc cttgttttac tagatacccc cccttaatgg 121740 gtgcgggggg gtcaggtctg cggggttggg atgggacctt aactccatat aaagcgagtc 121800 tggaaggggg gaaaggcgga cagtcgataa gtcggtagcg ggggacgcgc acctgttccg 121860 cctgtcgcac ccacagcttt ttcgcgaacc gtcccgtttc gggatgccgt gccgcccgtt 121920 gcagggcctg gtgctcgtgg gcctctgggt ctgtgccacc agcctggttg tccgtggccc 121980 cacggtcagt ctggtatcaa actcatttgt ggacgccggg gccttggggc ccgacggcgt 122040 agtggaggaa gacctgctta ttctcgggga gcttcgcttt gtgggggacc aggtccccca 122100 caccacctac tacgatgggg tcgtagagct gtggcactac cccatgggac acaaatgccc 122160 acgggtcgtg catgtcgtca cggtgaccgc gtgcccacgt cgccccgccg tggcatttgc 122220 cctgtgtcgc gcgaccgaca gcactcacag ccccgcatat cccaccctgg agctgaatct 122280 ggcccaacag ccgcttttgc gggtccggag ggcgacgcgt gactatgccg gggtgtacgt 122340 gttacgcgta tgggtcgggg acgcaccaaa cgccagcctg tttgtcctgg ggatggccat 122400 agccgccgaa ggtactctgg cgtacaacgg ctcggcccat ggctcctgcg acccgaaact 122460 gcttccgtct tcggccccgc gtctggcccc ggcgagcgta taccaacccg cccctaaccc 122520 ggcctccacc ccctcgacca ccacctccac cccctcgacc accatccccg ctccccaagc 122580 atcgaccaca cccttcccca cgggagaccc aaaaccccaa cctcacgggg tcaaccacga 122640 acccccatcg aatgccacgc gagcgacccg cgactcgcga tatgcgctaa cggtgaccca 122700 gataatccag atagccatcc ccgcgtccat tatagccctg gtgtttctgg ggagctgtat 122760 ttgctttata cacagatgtc aacgccgcta ccgacgctcc cgccgcccga tttacagccc 122820 ccagataccc acgggcatct catgcgcggt gaacgaagcg gccatggccc gcctcggagc 122880 cgagctcaaa tcgcatccga gcaccccccc caaatcccgg cgccggtcgt cacgcacgcc 122940 aatgccctcc ctgacggcca tcgccgaaga gtcggagccc gcgggggcgg ctgggcttcc 123000 gacgcccccc gtggacccca cgacatccac cccaacgcct cccctgttgg tataggtcca 123060 cggccactgg ccgggggcac cacataaccg accgcagtca ctgagttggg aataaaccgg 123120 tattatttac ctatatccgt gtatgtccat ttctttcttc cccccccccc ccggaaacca 123180 aagaaggaag caaagaatgg atgggaggag ttcaggaagc cggggagagg gcccgcggcg 123240 catttaaggc gttgttgtgt tgactttggc tcttctggcg ggttggtgcg gtgctgtttg 123300 ttgggctccc attttacccg aagatcggct gctatccccg ggacatggat cgcggggcgg 123360 tggtggggtt tcttctcggt gtttgtgttg tatcgtgctt ggcgggaacg cccaaaacgt 123420 cctggagacg ggtgagtgtc ggcgaggacg tttcgttgct tccagctccg gggcctacgg 123480 ggcgcggccc gacccagaaa ctactatggg ccgtggaacc cctggatggg tgcggcccct 123540 tacacccgtc gtgggtctcg ctgatgcccc ccaagcaggt gcccgagacg gtcgtggatg 123600 cggcgtgcat gcgcgctccg gtcccgctgg cgatggcgta cgcccccccg gccccatctg 123660 cgaccggggg tctacgaacg gacttcgtgt ggcaggagcg cgcggccgtg gttaaccgga 123720 gtctggttat tcacggggtc cgagagacgg acagcggcct gtataccctg tccgtgggcg 123780 acataaagga cccggctcgc caagtggcct cggtggtcct ggtggtgcaa ccggccccag 123840 ttccgacccc acccccgacc ccagccgatt acgacgagga tgacaatgac gagggcgagg 123900 acgaaagtct cgccggcact cccgccagcg ggaccccccg gctcccgcct ccccccgccc 123960 ccccgaggtc ttggcccagc gcccccgaag tctcacatgt gcgtggggtg accgtgcgta 124020 tggagactcc ggaagctatc ctgttttccc ccggggagac gttcagcacg aacgtctcca 124080 tccatgccat cgcccacgac gaccagacct actccatgga cgtcgtctgg ttgaggttcg 124140 acgtgccgac ctcgtgtgcc gagatgcgaa tatacgaatc gtgtctgtat cacccgcagc 124200 tcccagaatg tctgtccccg gccgacgcgc cgtgcgccgc gagtacgtgg acgtctcgcc 124260 tggccgtccg cagctacgcg gggtgttcca gaacaaaccc cccaccgcgc tgttcggccg 124320 aggctcacat ggagcccgtc ccggggctgg cgtggcaggc ggcctccgtc aatctggagt 124380 tccgggacgc gtccccacaa cactccggcc tgtatctgtg tgtggtgtac gtcaacgacc 124440 atattcacgc ctggggccac attaccatca gcaccgcggc gcagtaccgg aacgcggtgg 124500 tggaacagcc cctcccacag cgcggcgcgg atttggccga gcccacccac ccgcacgtcg 124560 gggcccctcc ccacgcgccc ccaacccacg gcgccctgcg gttaggggcg gtgatggggg 124620 ccgccctgct gctgtctgcg ctggggttgt cggtgtgggc gtgtatgacc tgttggcgca 124680 ggcgtgcctg gcgggcggtt aaaagcaggg cctcgggtaa ggggcccacg tacattcgcg 124740 tggccgacag cgagctgtac gcggactgga gctcggacag cgagggagaa cgcgaccagg 124800 tcccgtggct ggcccccccg gagagacccg actctccctc caccaatgga tccggctttg 124860 agatcttatc accaacggct ccgtctgtat acccccgtag cgacgggcat caatctcgcc 124920 gccagctcac aacctttgga tccggaaggc ccgatcgccg ttactcccag gcctccgatt 124980 cgtccgtctt ctggtaaggc gccccatccc gaggccccac gtcggtcgcc gaactgggcg 125040 accgccggcg aggtggacgt cggagacgag ctaatcgcga tttccgacga acgcggaccc 125100 ccccgacatg accgcccgcc cctcgccacg tcgaccgcgc cctcgccaca cccgcgaccc 125160 ccgggctaca cggccgttgt ctccccgatg gccctccagg ctgtcgacgc cccctccctg 125220 tttgtcgcct ggctggccgc tcggtggctc cggggggctt ccggcctggg ggccgtcctg 125280 tgtgggattg cgtggtatgt gacgtcaatt gcccgaggcg cacaaagggc cggtggtccg 125340 cctagccgca gcaaattaaa aatcgtgagt cacagcgacc gcaacttccc acccggagct 125400 ttcttccggc ctcgatgacg tcccggctct ccgatcccaa ctcctcagcg cgatccgaca 125460 tgtccgtgcc gctttatccc acggcctcgc cagtttcggt cgaagcctac tactcggaaa 125520 gcgaagacga ggcggccaac gacttcctcg tacgcatggg ccgccaacag tcggtattaa 125580 ggcgttgacg cagacgcacc cgctgcgtcg gcatggtgat cgcctgtctc ctcgtggccg 125640 ttctgtcggg cggatttggg gcgctcctga tgtggctgct ccgctaaaag accgcatcga 125700 cacgcgcgtc cttcttgtcg tctctcttcc cccccatcac cccgcaattt gcacccagcc 125760 tttaactaca ttaaattggg ttcgattggc aatgttgtct cccggttgat ttttgggtgg 125820 gtggggagtg ggtgggtggg gagtgggtgg gtggggagtg ggtgggtggg gagtgggtgg 125880 gtggggagtg ggtgggtggg gagtgggtgg gtggggagtg ggtgggtggg gagtgggtgg 125940 gtggggagtg ggtgggtggg gagtggcaag gaagaaacaa gcccgaccac cagacagaaa 126000 atgtaaccat acccaaaccg actctggggg ctgtttgtgg ggtcggaacc ataggatgaa 126060 caaaccaccc cgtacctccc gcacccaagg gtgcgggtgg ctcatcggca tctgtccggt 126120 atgggttgtt ccccacccac tcgcgttcgg acgtcttaga atcatggcgg ttttctatgc 126180 cgacatcggt tttctccccc gcaataagac acgatgcgat aaaatctgtt tgtaaaattt 126240 attaagggta caaattgccc tagcacaggg gtggggttag ggccgggtcc ccacacccaa 126300 acgcaccaaa cagatgcagg cagtgggtcg agtacagccc cgcgtacgaa cacgtcgatg 126360 cgtgtgtcag acagcaccag aaagcacagg ccatcaacag gtcgtgcatg tgtcggtggg 126420 tttggacgcg gggggccatg gtggtgataa agttaatggc cgccgtccgc cagggccaca 126480 ggggcgacgt ctcttggttg gcccggagcc actgggtgtg gaccagccgc gcgtggcggc 126540 ccaacatggc ccctgtagcc gggggcgggg gatcgcgcac gtttgcagcg cacatgcgag 126600 acacctcgac cacggttcga aagaaggccc ggtggtccgc gggcaacatc accaggtgcg 126660 caagcgcccg ggcgtccaga gggtagagcc ctgagtcatc cgaggttggc tcatcgcccg 126720 ggtcttgccg caagtgcgtg tgggttgggc ttccggtggg cgggacgcga accgcggtgt 126780 ggatcccgac gcgggcccga gcgtatgctc catcttgtgg ggagaagggg tctgggctcg 126840 ccaggggggc atacttgccc gggctataca gacccgcgag ccgtacgtgg ttcgcggggg 126900 gtgcgtgggg tccggggctc cctgggagac cggggttgtc gtggatccct ggggtcacgc 126960 ggtaccctgg ggtctctggg agctcgcggt actctgggtt ccctaggttc tcggggtggt 127020 cgcggaaccc ggggctcccg gggaacacgc ggtgtcctgg ggattgttgg cggtcggacg 127080 gcttcagatg gcttcgagat cgtagtgtcc gcaccgactc gtagtagacc cgaatctcca 127140 cattgccccg ccgcttgatc attatcaccc cgttgcgggg gtccggagat catgcgcggg 127200 tgtcctcgag gtgcgtgaac acctctgggg tgcatgccgg cggacggcac gccttttaag 127260 taaacatctg ggtcgcccgg cccaactggg gccgggggtt gggtctggct catctcgaga 127320 gacacggggg ggaaccaccc tccgcccaga gactcgggtg atggtcgtac ccgggactca 127380 acgggttacc ggattacggg gactgtcggt cacggtcccg ccggttcttc gatgtgccac 127440 acccaaggat gcgttggggg cgatttcggg cagcagcccg ggagagcgca gcaggggacg 127500 ctccgggtcg tgcacggcgg ttctggccgc ctcccggtcc tcacgccccc ttttattgat 127560 ctcatcgcgt acgtcggcgt acgtcctggg cccaacccgc atgttgtcca ggaaggtgtc 127620 cgccatttcc agggcccacg acatgctttt ccccccgacg agcaggaagc ggtccacgca 127680 acggtcgccg ccggtcgcct cgacgagggc gttcctcctg cgggaaggca cgaacgcggg 127740 tgagccccct cctccgcccc cgcgtccccc ctcctccgcc cccgcgtccc ccctcctccg 127800 cccccgcgtc ccccctcctc cgcccccgcg tcccccctcc tccgcccccg cgtcccccct 127860 cctctgccca cccaaggtgc ttacccgtgc aaaaaaggcg gaccggtggg tttctgtcgt 127920 cggaggcccc cggggtgcgt cccctgtgtt tcgtgggtgg ggtgggcggg tctttccccc 127980 ccgcgtccgc gtgtcccttt ccgatgcgat cccgatcccg agccggggcg tcgcgatgcc 128040 gacgccgtcc gctccgacgg ccctctgcga ctcccgctcc cggtccgcgt gctccgcagc 128100 cgctcccgtc gttcgtggct ggcgccgtct gcgggcgtcg gtcgcgccgg gcctttatgt 128160 gcgccggaga gacccgcccc ccgccgcccg ggtccgcccc cggggccggc gcggagtcgg 128220 gcacggcgcc agtgctcgca cttcgcccta ataatatata tatattggga cgaagtgcga 128280 acgcttcgcg ttctcacttc ttttacccgg cggccccgcc cccttggggc ggtcccgccc 128340 gccggccaat gggggggcgg caaggcgggc ggcccaaggg ccgcccgccg tcccgttggt 128400 cccggcgtcc ggcgggcggg accgggggcc cggggacggc caacgggcgc gcggggctcg 128460 tatctcatta ccgccgaacc gggaagtcgg ggcccgggcc ccgccccctg cccgttcctc 128520 gttagcatgc ggaacggaag cggaaaccgc cggatcgggc ggtaatgaga tgccatgcgg 128580 ggcggggcgc ggacccaccc gccctcgcgc cccgtccatg gcagatggcg cggatgggcg 128640 gggccggggg ttcgaccaac gggccgcggc cacgggcccc cggcgtgccg gcgtcggggc 128700 ggggtcgtgc ataatggaat tccgttcggg gtgggcccgc cggggggcgg ggggccggcg 128760 gcctccgctg ctcctccttc ccgccggccc ctgggactat atgagcccga ggacgccccg 128820 atcgtccaca cggagcgcgg ctgccgacac ggatccacga cccgacgcgg gaccgccaga 128880 gacagaccgt cagacgctcg ccgcgccggg acgccgatac gcggacgaag cgcgggaggg 128940 ggatcggccg tccctgtcct ttttccccac ccaagcatcg accggtccgc gctagttccg 129000 cgtcgacggc gggggtcgtc ggggtccgtg ggtctcgccc cctcccccca tcgagagtcc 129060 gtaggtgacc taccgtgcta cgtccgccgt cgcagccgta tccccggagg atcgccccgc 129120 atcggcgatg gcgtcggaga acaagcagcg ccccggctcc ccgggcccca ccgacgggcc 129180 gccgcccacc ccgagcccag accgcgacga gcggggggcc ctcgggtggg gcgcggagac 129240 ggaggagggc ggggacgacc ccgaccacga ccccgaccac ccccacgacc tcgacgacgc 129300 ccggcgggac gggagggccc ccgcggcggg caccgacgcc ggcgaggacg ccggggacgc 129360 cgtctcgtcg cgacagctgg ctctgctggc ctccatggta gaggaggccg tccggacgat 129420 cccgacgccc gaccccgcgg cctcgccgcc ccggaccccc gcctttctag ccgacgacga 129480 tgacggggac gagtacgacg acgcagccga cgccgccggc gaccgggccc cggcccgggg 129540 ccgcgaacgg gaggccccgc tacgcggcgc gtatccggac cccacggacc gcctgtcgcc 129600 gcgcccgccg gcccagccgc cgcggagacg tcgtcacggc cggcggcggc catcggcgtc 129660 atcgacctcg tcggactccg ggtcctcgtc ctcgtcgtcc gcatcctctt cgtcctcgtc 129720 gtccgacgag gacgaggacg acgacggcaa cgacgcggcc gaccacgcac gcgaggcgcg 129780 ggccgtcggg cggggtccgt cgagcgcggc gccggaagcc cccgggcgga cgccgccccc 129840 gcccgggcca ccccccctct ccgaggccgc gcccaagccc cgggcggcgg cgaggacccc 129900 cgcggcctcc gcgggccgca tcgagcgccg ccgggcccgc gcggcggtgg ccggccgcga 129960 cgccacgggc cgcttcacgg ccgggcagcc ccggcgggtc gagctggacg ccgacgcggc 130020 ctccggcgcc ttctacgcgc gctatcgcga cgggtacgtc agcggggagc cgtggcccgg 130080 cgccgggccc ccgcccccgg ggcgggtgct gtacggcggc ctgggcgaca gccgcccggg 130140 cctctggggg gcgcccgagg cggaggaggc gcgacgccgg ttcgaggcct cgggcgcccc 130200 ggcggccgtg tgggcgcccg agctgggcga cgccgcgcag cagtacgccc tgatcacgcg 130260 gctgctgtac accccggacg cggaggccat ggggtggctc cagaacccgc gcgtggtccc 130320 cggggacgtg gcgctggacc aggcctgctt ccggatctcg ggcgccgcgc gcaacagcag 130380 ctccttcatc accggcagcg tggcgcgggc cgtgccccac ctgggctacg ccatggcggc 130440 cggccgcttc ggctggggcc tggcgcacgc ggcggccgcc gtggccatga gccgccgata 130500 cgaccgcgcg cagaagggct tcctgctgac cagcctgcgc cgcgcctacg cgcccctgtt 130560 ggcgcgcgag aacgcggcgc tgacgggggc cgcggggagc cccggcgccg gcgcagatga 130620 cgagggggtc gccgccgtcg ccgccgccgc accgggcgag cgcgcggtgc ccgccgggta 130680 cggcgccgcg gggatcctcg ccgccctggg gcggctgtcc gccgcgcccg cctcccccgt 130740 ggggggcgac gaccccgacg ccgcccgcca cgccgacgcc gacgccgggc gccgcgccca 130800 ggccggccgc gtggccgtcg agtgcctggc cgcctgccgc gggatcctgg aggcgctggc 130860 cgagggcttc gacggcgacc tggcggccgt cccggggctg gccggggccc ggcccgccag 130920 ccccccgcgg ccggagggac ccgcgggccc cgcttccccg ccgccgccgc acgccgacgc 130980 gccccgcctg cgcgcgtggc tgcgcgagct gcggttcgtg cgcgacgcgc tggtgctcat 131040 gcgcctgcgc ggggacctgc gcgtggccgg cggcagcgag gccgccgtgg ccgccgtgcg 131100 cgccgtgagc ctggtcgccg gggccctggg ccccgcgctg ccgcgggacc cgcgcctgcc 131160 gagctccgcg gccgccgccg ccgcggacct gctgtttgag aaccagagcc tccgccccct 131220 gctggcggcg gcggccagcg caccggacgc cgccgacgcg ctggcggccg ccgccgcctc 131280 cgccgcgccg cgggaggggc gcaagcgcaa gagtcccggc ccggcccggc cgcccggagg 131340 cggcggcccg cgacccccga agacgaagaa gagcggcgcg gacgcccccg gctcggacgc 131400 ccgcgccccc ctccccgcgc ccccctccac gcccccgggg cccgagccca cccccgccca 131460 gcccgcggcg gcccggggcg ccgcggcgca ggcccgcccg cgccccgtgg cgctgtcgcg 131520 ccggcccgcc gagggccccg accccctggg cggctggcgg cggcagcccc gggggcccag 131580 ccacacggcg gcgcccgcgg ccgccgccct ggaggcctac tgctccccgc gcgccgtggc 131640 cgagctcacg gaccacccgc tgttccccgt cccctggcga ccggccctca tgtttgaccc 131700 gcgggccctg gcctcgatcg ccgcgcggtg cgccgggccc gcccccgccg cccaggccgc 131760 gtgcggcggc gacgacgacg agaaccccca cccccacggg gccgccgggg gccgcctctt 131820 tggccccctg cgcgcctcgg gcccgctgcg ccgcatggcg gcctggatgc gccagatccc 131880 cgaccccgag gacgtgcgcg tggtggtgct gtactcgccg ctgccgggcg aggacctggc 131940 cggcggcggg gcctcggggg ggccgccgga gtggtccgcc gagcgcggcg ggctgtcctg 132000 cctgctggcg gccctggcca accggctgtg cgggccggac acggccgcct gggcgggcaa 132060 ctggaccggc gcccccgacg tgtcggcgct gggcgcgcag ggcgtgctgc tgctgtccac 132120 gcgggacctg gccttcgccg gggccgtgga gtttctgggg ctgctcgcca gcgccggcga 132180 ccggcggctc atcgtggtca acaccgtgcg cgcctgcgac tggcccgccg acgggcccgc 132240 ggtgtcgcgg cagcacgcct acctggcgtg cgacctgctg cccgccgtgc agtgcgccgt 132300 gcgctggccg gcggcgcggg acctgcgccg cacggtgctg gcctcgggcc gcgtgttcgg 132360 cccgggggtc ttcgcgcgcg tggaggccgc gcacgcgcgc ctgtaccccg acgcgccgcc 132420 gctgcgcctg tgccgcggcg gcaacgtgcg ctaccgcgtg cgcacgcgct tcggcccgga 132480 cacgccggtg cccatgtccc cgcgcgagta ccgccgggcc gtgctgccgg cgctggacgg 132540 ccgggcggcg gcctcgggga ccaccgacgc catggcgccc ggcgcgccgg acttctgcga 132600 ggaggaggcc cactcgcacc gcgcctgcgc gcgctggggc ctgggcgcgc cgctgcggcc 132660 cgtgtacgtg gcgctggggc gcgaggcggt gcgcgccggc ccggcccggt ggcgcgggcc 132720 gcggagggac ttttgcgccc gcgccctgct ggagcccgac gacgacgccc ccccgctggt 132780 gctgcgcggc gacgacgacg acggcccggg ggccctgccg ccggcgccgc ccgggattcg 132840 ctgggcctcg gccacgggcc gcagcggcac cgtgctggcg gcggcggggg ccgtggaggt 132900 gctgggggcg gaggcgggct tggccacgcc cccgcgacgg gacgttgtgg actgggaagg 132960 cgcctgggac gaagacgacg gcggcgcgtt cgagggggac ggggtgctgt aacgggccgg 133020 gacggggcgg ggcgcttgtg aaacccgaag acgcaataaa cggcaacgac ctgattaagt 133080 tttgcagtag cgttgtttat tcgaggggcg ggagggggcg aggggcggga gggggcgagg 133140 ggcgggaggg ggcgaggggc gggagggggc gaggggcggg agggggcgag gggcgggagg 133200 gggcgagggg cgggaggggg cgaggggcgg gagggggcga ggggcgggag ggggcgaggg 133260 gcgggagggg gcgaggggcg ggagggggcg aggggcggga gggggcgagg ggcgggaggg 133320 ggcgaggggc gggagggggc gaggggcggg agggggcgag gggcgggagg gggcgagggg 133380 cgggaggggg cgaggggcgg gagggggcga ggggcgggag ggggcgaggg gcggtggtgg 133440 tgcgcgggcg cccccggagg gtttggatct ctgacctgag attggcggca ctgaggtaga 133500 gatgcccgaa cccccccgag ggagcgcggg acgcggctgg ggagggctgg ggctggggag 133560 ggctggggcc ggggagggct ggggccgggg agggctgggg ccggggaggg ctggggccgg 133620 ggagggctgg ggccggggag ggctggggct ggggagggct ggggctgggg aggggcggtg 133680 gtgtgtagca ggagcggtgt gttgcgccgg ggtacgtctg gaggagcggg aggtgcgcgg 133740 tgacgtgtgg atgaggaaca ggagttgttg cgcggtgagt tgtcgctgtg agttgtgttg 133800 ttgggcaggt gtggtggatg acgtgacgtg tgacgtgcgg attgcgccgt gctttgttgg 133860 tgttgtttta cctgtggcag cccgggcccc ccgcgggcgc gcgcgcgcgc aaaaaaggcg 133920 ggcggcggtc cgggcggcgt gcgcgcgcgc ggcgggcgtg gggggcgggg ccgcgggagc 133980 gggggaggag cgggggagga gcggggggag gagcgggggg aggagcgggg ggaggagcgg 134040 ggggaggagc ggggggagga gcggggggag gagcgggggg aggagcgggg ggaggagcgg 134100 ggggaggagc ggggggagga gcggggggag gagcgggggg aggagcgggg ggaggagcgg 134160 ggggaggagc ggggggagga gcgggggagg agcggccaga ccccggaaac gggccccccc 134220 caaaacacac cccccggggg tcgcgcgcgg ccctttaaag gcgggcggcg g 134271 <210> 5 <211> 74 <212> DNA <213> UL56-rpsL-neo primer <400> 5 acaggaatac cagaataatg accaccacaa tcgcgaccac cccaaataca ggcctggtga 60 tgatggcggg atcg 74 <210> 6 <211> 74 <212> DNA <213> UsIR-rpsL-neo primer <400> 6 cccgaggacg ccccgatcgt ccacacggag cgcggctgcc gacacggatc tcagaagaac 60 tcgtcaagaa ggcg 74 <210> 7 <211> 42 <212> DNA <213> UL55 S primer <400> 7 acgcgtcgac taaaaacaaa acatttcaaa caaatcgccc ca 42 <210> 8 <211> 74 <212> DNA <213> UsIR-rpsL neo AS primer <400> 8 cccgaggacg ccccgatcgt ccacacggag cgcggctgcc gacacggatc tcagaagaac 60 tcgtcaagaa ggcg 74 <210> 9 <211> 28 <212> DNA <213> rpsL neo S primer <400> 9 cggcatcgcc ctaaaattcg gcgtcctc 28 <210> 10 <211> 28 <212> DNA <213> rpsL neo AS primer <400> 10 aagaaccggg cgcccctgcg ctgacagc 28 <210> 11 <211> 32 <212> DNA <213> gC S primer <400> 11 cagatccgat gccggtttcg gaattccacc cg 32 <210> 12 <211> 31 <212> DNA <213> gC AS primer <400> 12 cgggttaaac acctggcggt cgtcctcgaa c 31 <210> 13 <211> 74 <212> DNA <213> ICP6 R-rpsL-neo S primer <400> 13 gttcctgtcg cgacacacgg cgccgctctg cggtattcgg gggggagggg ggcctggtga 60 tgatggcggg atcg 74 <210> 14 <211> 74 <212> DNA <213> ICP6 R-rpsL-neo AS primer <400> 14 agggtcccgt ccgccttctc cgtgacatac agggtcatgg attggctatg tcagaagaac 60 tcgtcaagaa ggcg 74 <210> 15 <211> 98 <212> DNA <213> dIR S primer <400> 15 acaggaatac cagaataatg accaccacaa tcgcgaccac cccaaataca gatccgtgtc 60 ggcagccgcg ctccgtgtgg acgatcgggg cgtcctcg 98 <210> 16 <211> 98 <212> DNA <213> dIR AS primer <400> 16 cgaggacgcc ccgatcgtcc acacggagcg cggctgccga cacggatctg tatttggggt 60 ggtcgcgatt gtggtggtca ttattctggt attcctgt 98

Claims (14)

  1. 단순 헤르페스 바이러스 1형(Herpes Simplex Virus type 1: HSV-1)의 게놈 영역 중 ICP6(Infected-cell protein 6)이 결실되고, UL(Unique Long) 영역과 US(Unique short) 영역 사이의 IR(Internal Repeat) 영역이 결실되고, UL56 유전자의 일부 뉴클레오티드 서열이 결실된 HSV-1 게놈을 가지는 재조합 HSV-1.
  2. 청구항 1에 있어서, 상기 재조합 HSV-1은 TRL(Terminal Repeat of Long region) 영역; UL1 내지 UL38 및 UL40 내지 UL56 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 UL 영역; US1 내지 US12 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 US 영역; 및 TRS(Terminal Repeat of Short Region) 영역으로 이루어진 군으로부터 선택되는 HSV-1의 하나 이상의 게놈 영역을 포함하는 것인 재조합 HSV-1.
  3. 청구항 1에 있어서, 상기 ICP6는 UL39 유전자인 것인 재조합 HSV-1.
  4. 청구항 1에 있어서, 상기 재조합 HSV-1의 게놈은 HSV-1의 ICP6 유전자의 뉴클레오티드 서열 중 서열번호 1의 뉴클레오티드 서열이 결실된 것인 재조합 HSV-1.
  5. 청구항 1에 있어서, 상기 IR 영역은 IRL(Internal Repeat of Long region) 영역 및 IRS(Internal Repeat of Short region) 영역을 포함하는 것인 재조합 HSV-1.
  6. 청구항 1에 있어서, 상기 재조합 HSV-1의 게놈은 HSV-1의 IR 영역의 뉴클레오티드 서열 중 서열번호 2의 뉴클레오티드 서열이 결실된 것인 재조합 HSV-1.
  7. 삭제
  8. 청구항 1에 있어서, 상기 결실된 UL56 유전자의 일부 뉴클레오티드 서열은 서열번호 3의 뉴클레오티드 서열인 것인 재조합 HSV-1.
  9. 청구항 1에 있어서, 상기 재조합 HSV-1의 게놈은 서열번호 4의 뉴클레오티드 서열을 포함하는 재조합 HSV-1.
  10. 청구항 1에 있어서, 상기 재조합 HSV-1은 암세포 또는 종양세포 특이성을 나타내는 것인 재조합 HSV-1.
  11. 청구항 1 내지 6 및 8 내지 10 중 어느 한 항에 따른 재조합 HSV-1의 게놈 뉴클레오티드 서열을 포함하는 재조합 HSV-1 벡터.
  12. 청구항 11에 있어서, 외래 유전자의 뉴클레오티드 서열을 추가적으로 포함하는 것인 재조합 HSV-1 벡터.
  13. ICP6, IR, 및 UL56 유전자의 일부 영역이 결실된 HSV-1의 게놈 뉴클레오티드 서열을 포함하는 재조합 HSV-1 벡터를 제조하는 단계; 및
    상기 벡터를 세포에 형질감염시켜 재조합 HSV-1를 수득하는 단계를 포함하는 재조합 HSV-1을 제조하는 방법.
  14. 청구항 13에 있어서, 상기 재조합 HSV-1 벡터는 TRL 영역; UL1 내지 UL38 및 UL40 내지 UL56 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 UL 영역; US1 내지 US12 중 하나 이상의 유전자의 뉴클레오티드 서열을 포함하는 US 영역; 및 TRS 영역으로 이루어진 군으로부터 선택되는 HSV-1의 하나 이상의 게놈 영역의 뉴클레오티드 서열을 포함하는 것인 방법.
KR1020180094006A 2018-08-10 2018-08-10 재조합 단순 헤르페스 바이러스 및 이의 제조방법 KR101974169B1 (ko)

Priority Applications (4)

Application Number Priority Date Filing Date Title
KR1020180094006A KR101974169B1 (ko) 2018-08-10 2018-08-10 재조합 단순 헤르페스 바이러스 및 이의 제조방법
PCT/KR2019/010068 WO2020032680A1 (ko) 2018-08-10 2019-08-09 재조합 단순 헤르페스 바이러스 및 이의 제조방법
CN201980051993.6A CN112534048A (zh) 2018-08-10 2019-08-09 重组单纯疱疹病毒和其制造方法
JP2021506935A JP7138234B2 (ja) 2018-08-10 2019-08-09 組み換え単純ヘルペスウイルス及びその製造方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR1020180094006A KR101974169B1 (ko) 2018-08-10 2018-08-10 재조합 단순 헤르페스 바이러스 및 이의 제조방법

Publications (1)

Publication Number Publication Date
KR101974169B1 true KR101974169B1 (ko) 2019-04-30

Family

ID=66285583

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020180094006A KR101974169B1 (ko) 2018-08-10 2018-08-10 재조합 단순 헤르페스 바이러스 및 이의 제조방법

Country Status (4)

Country Link
JP (1) JP7138234B2 (ko)
KR (1) KR101974169B1 (ko)
CN (1) CN112534048A (ko)
WO (1) WO2020032680A1 (ko)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020032680A1 (ko) * 2018-08-10 2020-02-13 의료법인 성광의료재단 재조합 단순 헤르페스 바이러스 및 이의 제조방법

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100237144B1 (ko) * 1991-01-31 2000-03-02 빌리 하킨 단순 포진 비루스-1 결실 변종 및 그의 제조 방법

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2361892C (en) * 1999-02-05 2010-05-25 Ralph Weichselbaum Treatment of tumors with genetically engineered herpes virus
JP2002218975A (ja) * 2001-01-26 2002-08-06 Yukihiro Nishiyama 弱毒化単純ヘルペスウイルス
AU2002307749A1 (en) * 2001-05-09 2002-11-25 M's Science Corporation Composition and method for treating cancer using herpes virus
CN101338302B (zh) * 2008-05-04 2011-06-01 罗益(无锡)生物制药有限公司 一种用于肿瘤基因治疗的重组单纯疱疹病毒
EP3981438A1 (en) * 2015-05-04 2022-04-13 The Brigham and Women's Hospital, Inc. Oncolytic hsv1 vector and methods of use
KR101974169B1 (ko) * 2018-08-10 2019-04-30 의료법인 성광의료재단 재조합 단순 헤르페스 바이러스 및 이의 제조방법

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100237144B1 (ko) * 1991-01-31 2000-03-02 빌리 하킨 단순 포진 비루스-1 결실 변종 및 그의 제조 방법

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Cancer Research. 2009, vol. 69. 1, No. 8, pp. 3472-3481.* *
J. gen. Virol. 1987, vol. 68, pp. 3019-3031.* *
Virus Research. 1996, vol. 40, issue 1, pp. 17-31.* *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020032680A1 (ko) * 2018-08-10 2020-02-13 의료법인 성광의료재단 재조합 단순 헤르페스 바이러스 및 이의 제조방법

Also Published As

Publication number Publication date
JP7138234B2 (ja) 2022-09-15
WO2020032680A1 (ko) 2020-02-13
JP2021532820A (ja) 2021-12-02
CN112534048A (zh) 2021-03-19

Similar Documents

Publication Publication Date Title
AU2019204982B2 (en) Recombinant HCMV and RhCMV Vectors and Uses Thereof
AU2018250519B2 (en) Compositions and methods for improving lettuce production
KR102563191B1 (ko) 비피도박테리움 애니멀리스 ssp. 락티스를 이용한 암 치료 조성물 및 방법
DK2753355T3 (en) ONCOLYTIC HERP SIMPLEX VIRUSES AND THERAPEUTIC APPLICATIONS THEREOF
CN100558896C (zh) 双岐杆菌的基因组
KR101763093B1 (ko) 시미안 아데노바이러스 핵산- 및 아미노산-서열, 이를 포함하는 벡터 및 이의 용도
AU2020227049A1 (en) Fast diagnosis and personalized treatments for acne
KR101668163B1 (ko) Cmv용 백신으로서의 조건부 복제 시토메갈로바이러스
AU2015289560B2 (en) Human cytomegalovirus comprising exogenous antigens
KR20190017751A (ko) 피부 장애의 치료를 위한 조성물 및 방법
CN110101723B (zh) 一种用于治疗肿瘤的伪狂犬病毒
WO1998020016A1 (en) Novel coding sequences from herpes simplex virus type-2
AU2021232778A1 (en) Oncolytic HSV1 vector and methods of use
JP2023145678A (ja) エプスタインバールウイルス抗原構築物
AU2016295122A1 (en) Genetic testing for predicting resistance of pseudomonas species against antimicrobial agents
KR101974169B1 (ko) 재조합 단순 헤르페스 바이러스 및 이의 제조방법
KR20210053923A (ko) 항종양 면역 반응을 자극하는 키메라 종양 용해성 허피스바이러스
CN116940589A (zh) 重组sars-cov-2疫苗
KR102039631B1 (ko) U38, u40 및 u41의 일부 서열을 포함하는 재조합 단순 헤르페스 바이러스 셔틀 벡터의 제조 방법
KR101998793B1 (ko) 재조합 단순 헤르페스 바이러스의 제조를 위한 벡터
KR102039633B1 (ko) Gm-csf 유전자를 포함하는 단순 재조합 헤르페스 바이러스 셔틀 벡터
KR102039634B1 (ko) U38, u340 및 u41의 일부 서열을 포함하는 재조합 단순 헤르페스 바이러스 셔틀 벡터
KR102039632B1 (ko) Icp 6 결실 및 gm-csf 유전자를 포함하는 재조합 단순 헤르페스 바이러스 셔틀 벡터의 제조 방법
KR102052718B1 (ko) Icp6 영역에 암 치료 유전자를 포함하는 셔틀벡터와 형질 전환 단계를 포함하는 hsv-1 벡터의 제조방법
CN117769595A (zh) 伪狂犬病病毒疫苗

Legal Events

Date Code Title Description
E701 Decision to grant or registration of patent right
GRNT Written decision to grant