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PMID: 17943122 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A second generation human haplotype map of over 3.1 million SNPs.

Nature ·Vol. 449 ·No. 7164 ·2007-10-18 ·Pages 851-61

International HapMap Consortium, 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 MM, Tsui SK, Xue H, Wong JT, Galver LM, Fan JB, Gunderson K, Murray SS, Oliphant AR, Chee MS, Montpetit A, Chagnon F, Ferretti V, Leboeuf M, Olivier JF, Phillips MS, Roumy S, Sallée C, Verner A, Hudson TJ, Kwok PY, Cai D, Koboldt DC, Miller RD, Pawlikowska L, Taillon-Miller P, Xiao M, Tsui LC, Mak W, Song YQ, Tam PK, 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 PI, 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 CD, 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

Abstract

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.

MeSH Terms
Female Haplotypes/genetics Homozygote Humans Linkage Disequilibrium/genetics Male Polymorphism, Single Nucleotide/genetics Racial Groups/genetics Recombination, Genetic/genetics Selection, Genetic
Authors & Affiliations
251 authors, click to expand affiliations / ORCID
International HapMap Consortium
The Scripps Research Institute, 10550 North Torrey Pines Road MEM275, La Jolla, California 92037, USA.
Frazer Kelly A
Ballinger Dennis G
Cox David R
Hinds David A
Stuve Laura L
Gibbs Richard A
Belmont John W
Boudreau Andrew
Hardenbol Paul
Leal Suzanne M
Pasternak Shiran
Wheeler David A
Willis Thomas D
Yu Fuli
Yang Huanming
Zeng Changqing
Gao Yang
Hu Haoran
Hu Weitao
Li Chaohua
Lin Wei
Liu Siqi
Pan Hao
Tang Xiaoli
Wang Jian
Wang Wei
Yu Jun
Zhang Bo
Zhang Qingrun
Zhao Hongbin
Zhao Hui
Zhou Jun
Gabriel Stacey B
Barry Rachel
Blumenstiel Brendan
Camargo Amy
Defelice Matthew
Faggart Maura
Goyette Mary
Gupta Supriya
Moore Jamie
Nguyen Huy
Onofrio Robert C
Parkin Melissa
Roy Jessica
Stahl Erich
Winchester Ellen
Ziaugra Liuda
Altshuler David
Shen Yan
Yao Zhijian
Huang Wei
Chu Xun
He Yungang
Jin Li
Liu Yangfan
Shen Yayun
Sun Weiwei
Wang Haifeng
Wang Yi
Wang Ying
Xiong Xiaoyan
Xu Liang
Waye Mary M Y
Tsui Stephen K W
Xue Hong
Wong J Tze-Fei
Galver Luana M
Fan Jian-Bing
Gunderson Kevin
Murray Sarah S
Oliphant Arnold R
Chee Mark S
Montpetit Alexandre
Chagnon Fanny
Ferretti Vincent
Leboeuf Martin
Olivier Jean-François
Phillips Michael S
Roumy Stéphanie
Sallée Clémentine
Verner Andrei
Hudson Thomas J
Kwok Pui-Yan
Cai Dongmei
Koboldt Daniel C
Miller Raymond D
Pawlikowska Ludmila
Taillon-Miller Patricia
Xiao Ming
Tsui Lap-Chee
Mak William
Song You Qiang
Tam Paul K H
Nakamura Yusuke
Kawaguchi Takahisa
Kitamoto Takuya
Morizono Takashi
Nagashima Atsushi
Ohnishi Yozo
Sekine Akihiro
Tanaka Toshihiro
Tsunoda Tatsuhiko
Deloukas Panos
Bird Christine P
Delgado Marcos
Dermitzakis Emmanouil T
Gwilliam Rhian
Hunt Sarah
Morrison Jonathan
Powell Don
Stranger Barbara E
Whittaker Pamela
Bentley David R
Daly Mark J
de Bakker Paul I W
Barrett Jeff
Chretien Yves R
Maller Julian
McCarroll Steve
Patterson Nick
Pe'er Itsik
Price Alkes
Purcell Shaun
Richter Daniel J
Sabeti Pardis
Saxena Richa
Schaffner Stephen F
Sham Pak C
Varilly Patrick
Altshuler David
Stein Lincoln D
Krishnan Lalitha
Smith Albert Vernon
Tello-Ruiz Marcela K
Thorisson Gudmundur A
Chakravarti Aravinda
Chen Peter E
Cutler David J
Kashuk Carl S
Lin Shin
Abecasis Gonçalo R
Guan Weihua
Li Yun
Munro Heather M
Qin Zhaohui Steve
Thomas Daryl J
McVean Gilean
Auton Adam
Bottolo Leonardo
Cardin Niall
Eyheramendy Susana
Freeman Colin
Marchini Jonathan
Myers Simon
Spencer Chris
Stephens Matthew
Donnelly Peter
Cardon Lon R
Clarke Geraldine
Evans David M
Morris Andrew P
Weir Bruce S
Tsunoda Tatsuhiko
Mullikin James C
Sherry Stephen T
Feolo Michael
Skol Andrew
Zhang Houcan
Zeng Changqing
Zhao Hui
Matsuda Ichiro
Fukushima Yoshimitsu
Macer Darryl R
Suda Eiko
Rotimi Charles N
Adebamowo Clement A
Ajayi Ike
Aniagwu Toyin
Marshall Patricia A
Nkwodimmah Chibuzor
Royal Charmaine D M
Leppert Mark F
Dixon Missy
Peiffer Andy
Qiu Renzong
Kent Alastair
Kato Kazuto
Niikawa Norio
Adewole Isaac F
Knoppers Bartha M
Foster Morris W
Clayton Ellen Wright
Watkin Jessica
Gibbs Richard A
Belmont John W
Muzny Donna
Nazareth Lynne
Sodergren Erica
Weinstock George M
Wheeler David A
Yakub Imtaz
Gabriel Stacey B
Onofrio Robert C
Richter Daniel J
Ziaugra Liuda
Birren Bruce W
Daly Mark J
Altshuler David
Wilson Richard K
Fulton Lucinda L
Rogers Jane
Burton John
Carter Nigel P
Clee Christopher M
Griffiths Mark
Jones Matthew C
McLay Kirsten
Plumb Robert W
Ross Mark T
Sims Sarah K
Willey David L
Chen Zhu
Han Hua
Kang Le
Godbout Martin
Wallenburg John C
L'Archevêque Paul
Bellemare Guy
Saeki Koji
Wang Hongguang
An Daochang
Fu Hongbo
Li Qing
Wang Zhen
Wang Renwu
Holden Arthur L
Brooks Lisa D
McEwen Jean E
Guyer Mark S
Wang Vivian Ota
Peterson Jane L
Shi Michael
Spiegel Jack
Sung Lawrence M
Zacharia Lynn F
Collins Francis S
Kennedy Karen
Jamieson Ruth
Stewart John
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
Published
2007-10-18
Pages
851-61
Language
English
Region
England
NLM ID
0410462
PMCID
PMC2689609
Subset
IM
Grants
Wellcome Trust · 077008 · United Kingdom
Wellcome Trust · 077011 · United Kingdom
Wellcome Trust · 077046 · United Kingdom
Wellcome Trust · United Kingdom
Wellcome Trust · 081682 · United Kingdom
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