title: Imprinting in Prader-Willi and Angelman syndromes.
abstract: Imprinted genes are marked in the germline and retain molecular memory of their parental origin, resulting in allelic expression differences during development. Abnormalities in imprinted inheritance occur in several genetic diseases and cancer, and are exemplified by the diverse genetic defects involving chromosome 15q11-q13 in Prader-Willi (PWS) and Angelman (AS) syndromes. PWS involves loss of function of multiple paternally expressed genes, while mutations in a single gene, UBE3A, which is subject to spatially restricted imprinting, occur in some AS patients. Identification of mutations in the imprinting process in PWS and AS has led to a definition of an imprinting center (IC), involving the promoter (in PWS) or an alternative transcript of the SNRPN gene (in AS). The IC regulates initiation of imprint switching for all genes in a 2 Mb imprinted domain during gametogenesis. Imprinting mutations define a novel mechanism of genetic disease because they have no direct effect in the affected patient but, rather, it is the parental germline effect of an IC mutation that leads to disease in the offspring.
authors.affiliation: Department of Genetics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Nicholls
authors.forename: S
authors.initials: S
authors.lastname: Saitoh
authors.forename: B
authors.initials: B
authors.lastname: Horsthemke
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics*; D000818:Animals; D005075:Biological Evolution; D017124:Conserved Sequence; D018392:Genomic Imprinting; D006801:Humans; D008025:Ligases / Q000235:genetics; D051379:Mice; D009154:Mutation; D011218:Prader-Willi Syndrome / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; D008025:Ligases