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Initial Genome Scan of the NIMH Genetics Initiative Bipolar Pedigrees: Chromosomes 4, 7, 9, 18, 19, 20, and 21q
Authors:Sevilla D. Detera-Wadleigh  Judith A. Badner  Takeo Yoshikawa  Alan R. Sanders  Lynn R. Goldin  Gordon Turner  Denise Y. Rollins  Tracy Moses  Juliet J. Guroff  Diane Kazuba  Mary E. Maxwell  Howard J. Edenberg  Tatiana Foroud  Debomoy Lahiri  John I. Nurnberger  O. Colin Stine  Francis McMahon  Deborah A. Meyers  Dean MacKinnon  Sylvia Simpson  Melvin McInnis  J. Raymond DePaulo  John Rice  Alison Goate  Theodore Reich  Mary C. Blehar  Elliot S. Gershon
Abstract:An initial genome scan was performed on 540 individuals from 97 families segregating bipolar disorder, collected through the National Institutes of Mental Health Genetics Initiative. We report here affected-sib-pair (ASP) data on 126 marker loci (≈68,000 genotypes) mapping to chromosomes 4, 7, 9, 18, 19, 20, and 21q, under three affection status models. Modest increases in identical-by-descent (IBD) allele sharing were found at the following loci: D4S2397 and D4S391 ( P < 0.05) on 4p, D4S1647 ( P < 0.05) on 4q, D7S1802 and D7S1869 (low P = 0.01) on 7p, D9S302 ( P = 0.004) on 9q, and D20S604 on 20p and D20S173 on 20q ( P ≤ 0.05). In addition, five markers on 7q displayed increased IBD sharing ( P = 0.046–0.002). Additional ASP analyses on chromosomes 18 and 21q marker data were performed using disease phenotype models defined previously. On chromosome 18, only D18S40 on 18p and D18S70 on 18q yielded a slight elevation in allele sharing ( P = 0.02), implying that the reported linkages in these regions were not confirmed. On chromosome 21q, a cluster of markers within an ≈9 cM interval: D21S1254, D21S65, D21S1440, and D21S1255 exhibited excess allele sharing ( P = 0.041–0.008). Multilocus data on overlapping marker quartets, from D21S1265 to D21S1255, which were consistent with increased IBD sharing ( P < 0.01, with a low of 0.0009), overlapped a broad interval of excess allele sharing reported previously, increasing support for a susceptibility locus for bipolar disorder on 21q. Am. J. Med. Genet. 74:254–262, 1997. © 1997 Wiley-Liss, Inc.
Keywords:bipolar pedigree  genome scan  bipolar disorder  linkage
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