RECORD NO.: 95315990 AUTHOR: Buiting K; Saitoh S; Gross S; Dittrich B; Schwartz S; Nicholls RD; Horsthemke B ADDRESS: Institut fur Humangenetik, Universitatsklinikum Essen, Germany. TITLE: Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15. SOURCE: Nat Genet (BRO), 1995 Apr; 9 (4): 395-400 LANGUAGE: English COUNTRY PUB.: UNITED STATES ANNOUNCEMENT: 9510 PUB. TYPE: JOURNAL ARTICLE ABSTRACT: 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. MESH HEADINGS: Angelman Syndrome--genetics (*GE); *Chromosomes, Human, Pair 15; *Genomic Imprinting; Prader-Willi Syndrome--genetics (*GE); *Sequence Deletion; Autoantigens--genetics (GE); DNA-- chemistry (CH)/genetics (GE); DNA Probes; Gene Expression; Methylation; Models, Genetic; Pedigree; Restriction Mapping; Ribonucleoproteins, Small Nuclear--genetics (GE); Female; Human; Male; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S. GENE SYMBOL: SNRPN; PAR-1; PAR-5 CHEMICAL SUBS: 0 (Autoantigens); 0 (DNA Probes); 0 (Ribonucleoproteins, Small Nuclear); 0 (Sm antigen); 9007-49-2 (DNA) GRANT NO.: HD31491; HD; NICHD STANDARD NO.: 1061-4036 DATES: Entered 950803