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