Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15

Nat Genet. 1995 Apr;9(4):395-400. doi: 10.1038/ng0495-395.


A subset of patients with Angelman and Prader-Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DNA methylation at several loci within chromosome 15q11-13, and probably have a defect in imprinting. Using probes from a newly established 160-kb contig including D15S63 (PW71) and SNRPN, we have identified inherited microdeletions in two AS families and three PWS families. The deletions probably affect a single genetic element that we term the 15q11-13 imprinting centre (IC). In our model, the IC regulates the chromatin structure, DNA methylation and gene expression in cis throughout 15q11-13. Mutations of the imprinting centre can be transmitted silently through the germline of one sex, but appear to block the resetting of the imprint in the germline of the opposite sex.

Publication types

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

MeSH terms

  • Angelman Syndrome / genetics*
  • Autoantigens / genetics
  • Chromosomes, Human, Pair 15*
  • DNA / chemistry
  • DNA / genetics
  • DNA Probes
  • Female
  • Gene Expression
  • Genomic Imprinting*
  • Humans
  • Male
  • Methylation
  • Models, Genetic
  • Pedigree
  • Prader-Willi Syndrome / genetics*
  • Restriction Mapping
  • Ribonucleoproteins, Small Nuclear / genetics
  • Sequence Deletion*
  • snRNP Core Proteins


  • Autoantigens
  • DNA Probes
  • Ribonucleoproteins, Small Nuclear
  • SNRPN protein, human
  • snRNP Core Proteins
  • DNA