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Hinch AG Tandon A Patterson N Song Y Rohland N Palmer CD Chen GK Wang K Buxbaum SG Akylbekova EL Aldrich MC Ambrosone CB Amos C Bandera EV Berndt SI Bernstein L Blot WJ Bock CH Boerwinkle E Cai Q Caporaso N Casey G Cupples LA Deming SL Diver WR Divers J Fornage M Gillanders EM Glessner J Harris CC Hu JJ Ingles SA Isaacs W John EM Kao WH Keating B Kittles RA Kolonel LN Larkin E Le Marchand L McNeill LH Millikan RC Murphy A Musani S Neslund-Dudas C Nyante S Papanicolaou GJ Press MF Psaty BM 《Nature》2011,476(7359):170-175
Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P?value 10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution. 相似文献
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Haiman CA Chen GK Blot WJ Strom SS Berndt SI Kittles RA Rybicki BA Isaacs WB Ingles SA Stanford JL Diver WR Witte JS Hsing AW Nemesure B Rebbeck TR Cooney KA Xu J Kibel AS Hu JJ John EM Gueye SM Watya S Signorello LB Hayes RB Wang Z Yeboah E Tettey Y Cai Q Kolb S Ostrander EA Zeigler-Johnson C Yamamura Y Neslund-Dudas C Haslag-Minoff J Wu W Thomas V Allen GO Murphy A Chang BL Zheng SL Leske MC Wu SY Ray AM Hennis AJ Thun MJ Carpten J Casey G Carter EN Duarte ER Xia LY Sheng X Wan P Pooler LC 《Nature genetics》2011,43(6):570-573
In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ~5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations. 相似文献
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