A second generation human haplotype map of over 3.1 million SNPs.
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., 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.
We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.