Genomic imprinting and uniparental disomy in Angelman and Prader-Willi syndromes: a review.
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.
Department of Neuroscience, University of Florida College of Medicine, Gainesville 32610.
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D017204:Angelman Syndrome / Q000235:genetics*; D000818:Animals; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D004195:Disease Models, Animal; D005220:Fathers; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D017496:Hypopigmentation / Q000235:genetics; D008297:Male; D051379:Mice; D009035:Mothers; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics; D014178:Translocation, Genetic
D011963:Receptors, GABA-A