Identification and uniparental expression of a novel gene from the Prader-Willi region of chromosome 15
- Stanford Univ., CA (United States)
The Prader-Willi syndrome (PWS) is a neurobehavioral disorder which occurs at a frequency of about 1/25,000. Most patients ({approximately}70%) have a cytogentic deletion of their paternal 15q11-q13 region, while {approximately}30% have uniparental maternal disomy. The parent of origin dependence of the phenotype is thought to be reflective of the uniparental pattern of expression of genes in the region, a phenomenon known as genomic imprinting. A small subset of PWS patient with a typical cytogenetic rearrangements has defined a critical region for genes involved in PWS. We have used STSs from the region to construct a YAC contig including the entire PWS critical region, which is about 350 kb considering presently characterized deletions. We are now using these YACs to isolate and characterize novel genes potentially involved in PWS. Overlapping YACs from the critical region were subjected to the technique of cDNA selection. Gel-purified YAC DNA was biotinylated during PCR amplification and annealed in solution to amplified cDNA. cDNAs remaining after hybridization washing, and denaturation of the hybrids were tested for localization within the YAC contig. One such cDNA mapped back to the YAC contig and was further analyzed. A full length cDNA clone was isolated from a fetal brain library and sequenced. The pattern of expression was determined in cell lines derived from Prader-Willi and Angelman patients and in normal individuals. The gene was found to have monoallelic, paternal expression in normal individuals and is marginally or not expressed in cell lines derived form Prader-Willi individuals. Expression in cell lines from Angelman patients, who are deleted for the same region on the maternal chromosome 15, was normal. Thus this apparently maternally imprinted gene is a candidate for involvement in the Prader-Willi phenotype.
- OSTI ID:
- 133381
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0109
- Journal Information:
- American Journal of Human Genetics, Vol. 55, 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
- Country of Publication:
- United States
- Language:
- English
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