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Title: Deletions of a differentially methylated CpG island at SNRPN define a putative imprinting control region

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with paternal and maternal deficiencies, respectively, of gene expression within human chromosome 15q11-q13, and are caused by deletion, uniparental disomy, or other mutations. Four transcripts designated PAR-5, PAR-7, PAR-1 and PAR-4 were isolated and localized to a region within 300 kb telomeric to the gene encoding small nuclear ribonucleoprotein-associated polypeptide N (SNRPN). Analysis of the transcripts in cultured fibroblasts and lymphoblasts from deletion patients demonstrated that SNRPN, PAR-5 and PAR-1 are expressed exclusively from the paternal chromosome, defining an imprinted domain that spans at least 200 kb. All three imprinted transcripts were absent in cells from three PWS patients (one pair of sibs and one sporadic case) with small deletions that involve a differentially methylated CpG island containing a previously undescribed 5{prime} untranslated exon ({alpha}) of SNRPN. Methylation of the CpG island is specific for the maternal chromosome consistent with paternal expression of the imprinted domain. One deletion, which is benign when maternally transmitted, extends upstream <30 kb from the CpG island, and is associated with altered methylation centromeric to SNRPN, and loss of transcription telomeric to SNRPN, implying the presence of an imprinting control region around the CpG island containingmore » exon {alpha}.« less
Authors:
; ;  [1]
  1. Baylor College of Medicine, Houston, TX (United States) [and others
Publication Date:
OSTI Identifier:
133378
Report Number(s):
CONF-941009--
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0106
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; TRANSCRIPTION; HUMAN CHROMOSOME 15; GENETIC MAPPING; CHROMOSOMAL ABERRATIONS; PATIENTS; HEREDITARY DISEASES; NERVOUS SYSTEM DISEASES; DNA; METHYLATION; GENETICS; CENTROMERES; TELOMERES