Mechanisms of imprinting of the Prader-Willi/Angelman region

Am J Med Genet A. 2008 Aug 15;146A(16):2041-52. doi: 10.1002/ajmg.a.32364.


Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct neurodevelopmental disorders, each caused by several genetic and epigenetic mechanisms involving the proximal long arm of chromosome 15. Lack of a functional paternal copy of 15q11-q13 causes PWS; lack of a functional maternal copy of UBE3A, a gene within 15q11-q13, causes AS. This region of chromosome 15 contains a number of imprinted genes that are coordinately regulated by an imprinting center (PWS/AS-IC) that contains two functional elements, the PWS-SRO and the AS-SRO. A chromosome lacking the PWS-SRO has the maternal state of gene activity and epigenetic modification after either maternal or paternal transmission; a chromosome lacking the AS-SRO but containing the PWS-SRO has the paternal state of gene activity and epigenetic modification after either maternal or paternal transmission. The maternal state of chromosome 15q11-q13 is associated with methylation of the PWS-SRO, while the paternal state is associated with lack of methylation of the PWS-SRO. Although most models of PWS/AS region imprinting assume that the PWS-SRO is methylated during oogenesis and that this methylation of the maternal PWS-SRO is maintained after fertilization, several lines of evidence suggest that the maternal PWS-SRO is in fact not methylated until after fertilization. Imprinting defects affecting the PWS/AS region can arise from failure to demethylate the PWS-SRO in the male germ line, from failure to methylate the maternal PWS-SRO, or from failure to maintain PWS-SRO methylation after fertilization.

Publication types

  • Review

MeSH terms

  • Angelman Syndrome / genetics*
  • Animals
  • Chromosomes, Human, Pair 15 / genetics
  • DNA Methylation
  • Epigenesis, Genetic
  • Gene Deletion
  • Genomic Imprinting*
  • Humans
  • Mice
  • Models, Genetic
  • Prader-Willi Syndrome / genetics*
  • RNA, Antisense / genetics
  • Ubiquitin-Protein Ligases / genetics


  • RNA, Antisense
  • UBE3A protein, human
  • Ubiquitin-Protein Ligases