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Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction

Birth Defects Res C Embryo Today. 2005 Jun;75(2):81-97. doi: 10.1002/bdrc.20039.

Abstract

Imprinted genes play important roles in the regulation of growth and development, and several have been shown to influence behavior. Their allele-specific expression depends on inheritance from either the mother or the father, and is regulated by "imprinting control regions" (ICRs). ICRs are controlled by DNA methylation, which is present on one of the two parental alleles only. These allelic methylation marks are established in either the female or the male germline, following the erasure of preexisting DNA methylation in the primordial germ cells. After fertilization, the allelic DNA methylation at ICRs is maintained in all somatic cells of the developing embryo. This epigenetic "life cycle" of imprinting (germline erasure, germline establishment, and somatic maintenance) can be disrupted in several human diseases, including Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS), Angelman syndrome and Hydatidiform mole. In the neurodevelopmental Rett syndrome, the way the ICR mediates imprinted expression is perturbed. Recent studies indicate that assisted reproduction technologies (ART) can sometimes affect the epigenetic cycle of imprinting as well, and that this gives rise to imprinting disease syndromes. This finding warrants careful monitoring of the epigenetic effects, and absolute risks, of currently used and novel reproduction technologies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • DNA Methylation
  • Diseases in Twins
  • Epigenesis, Genetic*
  • Female
  • Genetic Diseases, Inborn / genetics*
  • Genomic Imprinting*
  • Humans
  • Male
  • Models, Genetic
  • Reproductive Techniques, Assisted / adverse effects*
  • Rett Syndrome / genetics
  • Risk