Genome-wide detection and characterization of positive selection in human populations.
Sabeti PC., Varilly P., Fry B., Lohmueller J., Hostetter E., Cotsapas C., Xie X., Byrne EH., McCarroll SA., Gaudet R., Schaffner SF., Lander ES., International HapMap Consortium None., Frazer KA., Ballinger DG., Cox DR., Hinds DA., Stuve LL., Gibbs RA., Belmont JW., Boudreau A., Hardenbol P., Leal SM., Pasternak S., Wheeler DA., Willis TD., Yu F., Yang H., Zeng C., Gao Y., Hu H., Hu W., Li C., Lin W., Liu S., Pan H., Tang X., Wang J., Wang W., Yu J., Zhang B., Zhang Q., Zhao H., Zhao H., Zhou J., Gabriel SB., Barry R., Blumenstiel B., Camargo A., Defelice M., Faggart M., Goyette M., Gupta S., Moore J., Nguyen H., Onofrio RC., Parkin M., Roy J., Stahl E., Winchester E., Ziaugra L., Altshuler D., Shen Y., Yao Z., Huang W., Chu X., He Y., Jin L., Liu Y., Shen Y., Sun W., Wang H., Wang Y., Wang Y., Xiong X., Xu L., Waye MMY., Tsui SKW., Xue H., Wong JT-F., Galver LM., Fan J-B., Gunderson K., Murray SS., Oliphant AR., Chee MS., Montpetit A., Chagnon F., Ferretti V., Leboeuf M., Olivier J-F., Phillips MS., Roumy S., Sallée C., Verner A., Hudson TJ., Kwok P-Y., Cai D., Koboldt DC., Miller RD., Pawlikowska L., Taillon-Miller P., Xiao M., Tsui L-C., Mak W., Song YQ., Tam PKH., Nakamura Y., Kawaguchi T., Kitamoto T., Morizono T., Nagashima A., Ohnishi Y., Sekine A., Tanaka T., Tsunoda T., Deloukas P., Bird CP., Delgado M., Dermitzakis ET., Gwilliam R., Hunt S., Morrison J., Powell D., Stranger BE., Whittaker P., Bentley DR., Daly MJ., de Bakker PIW., Barrett J., Chretien YR., Maller J., McCarroll S., Patterson N., Pe'er I., Price A., Purcell S., Richter DJ., Sabeti P., Saxena R., Schaffner SF., Sham PC., Varilly P., Altshuler D., Stein LD., Krishnan L., Smith AV., Tello-Ruiz MK., Thorisson GA., Chakravarti A., Chen PE., Cutler DJ., Kashuk CS., Lin S., Abecasis GR., Guan W., Li Y., Munro HM., Qin ZS., Thomas DJ., McVean G., Auton A., Bottolo L., Cardin N., Eyheramendy S., Freeman C., Marchini J., Myers S., Spencer C., Stephens M., Donnelly P., Cardon LR., Clarke G., Evans DM., Morris AP., Weir BS., Tsunoda T., Johnson TA., Mullikin JC., Sherry ST., Feolo M., Skol A., Zhang H., Zeng C., Zhao H., Matsuda I., Fukushima Y., Macer DR., Suda E., Rotimi CN., Adebamowo CA., Ajayi I., Aniagwu T., Marshall PA., Nkwodimmah C., Royal CDM., Leppert MF., Dixon M., Peiffer A., Qiu R., Kent A., Kato K., Niikawa N., Adewole IF., Knoppers BM., Foster MW., Clayton EW., Watkin J., Gibbs RA., Belmont JW., Muzny D., Nazareth L., Sodergren E., Weinstock GM., Wheeler DA., Yakub I., Gabriel SB., Onofrio RC., Richter DJ., Ziaugra L., Birren BW., Daly MJ., Altshuler D., Wilson RK., Fulton LL., Rogers J., Burton J., Carter NP., Clee CM., Griffiths M., Jones MC., McLay K., Plumb RW., Ross MT., Sims SK., Willey DL., Chen Z., Han H., Kang L., Godbout M., Wallenburg JC., L'Archevêque P., Bellemare G., Saeki K., Wang H., An D., Fu H., Li Q., Wang Z., Wang R., Holden AL., Brooks LD., McEwen JE., Guyer MS., Wang VO., Peterson JL., Shi M., Spiegel J., Sung LM., Zacharia LF., Collins FS., Kennedy K., Jamieson R., Stewart J.
With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.