Genomic imprinting and uniparental disomy in Angelman and Prader-Willi syndromes: a review

Am J Med Genet. 1993 Apr 1;46(1):16-25. doi: 10.1002/ajmg.1320460106.

Abstract

Although Angelman (AS) and Prader-Willi (PWS) syndromes are human genetic disorders with distinctly different developmental and neurobehavioural phenotypes, they both have abnormalities in inheritance of chromosome 15q11-q13. Whether AS or PWS arises depends on the parental origin of a deletion or uniparental disomy (the inheritance of 2 copies of a genetic locus from only one parent) for 15q11-q13. Normal development requires a genetic contribution for this genetic region from both a male and a female parent. The dependence on parental origin implies that genes in human 15q11-q13 have distinct functions depending upon epigenetic, parent-of-origin differences, known as genomic imprinting. Here, I review the role of uniparental disomy and genomic imprinting in the pathogenesis of AS and PWS, and briefly discuss phenotype-genotype correlations using candidate genes and mouse models, in particular for hypopigmentation.

Publication types

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

MeSH terms

  • Angelman Syndrome / genetics*
  • Animals
  • Chromosome Deletion*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15*
  • Disease Models, Animal
  • Fathers
  • Female
  • Gene Expression Regulation*
  • Genotype
  • Humans
  • Hypopigmentation / genetics
  • Male
  • Mice
  • Mothers
  • Phenotype
  • Prader-Willi Syndrome / genetics*
  • Receptors, GABA-A / genetics
  • Translocation, Genetic

Substances

  • Receptors, GABA-A