A second generation human haplotype map of over 3.1 million SNPs

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

doi:10.1038/nature06258

A second generation human haplotype map of over 3.1 million SNPs

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

Research output: Contribution to journal › Article › peer-review

3335 Scopus citations

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.

Original language	English (US)
Pages (from-to)	851-861
Number of pages	11
Journal	Nature
Volume	449
Issue number	7164
DOIs	https://doi.org/10.1038/nature06258
State	Published - Oct 18 2007
Externally published	Yes

ASJC Scopus subject areas

General

Access to Document

10.1038/nature06258

Cite this

Frazer, K. A., Ballinger, D. G., Cox, D. R., Hinds, D. A., Stuve, L. L., Gibbs, R. A., Belmont, J. W., Boudreau, A., Hardenbol, P., Leal, S. M., Pasternak, S., Wheeler, D. A., Willis, T. D., Yu, F., Yang, H., Zeng, C., Gao, Y., Hu, H., Hu, W., ... Stewart, J. (2007). A second generation human haplotype map of over 3.1 million SNPs. Nature, 449(7164), 851-861. https://doi.org/10.1038/nature06258

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, JTF, 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, You, QS, 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, 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, Johnson, TA, Mullikin, JC, Sherry, ST, Feolo, M, Skol, A, Zhang, 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, Muzny, D, Nazareth, L, Sodergren, E, Weinstock, GM, Yakub, I, Birren, BW, 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 2007, 'A second generation human haplotype map of over 3.1 million SNPs', Nature, vol. 449, no. 7164, pp. 851-861. https://doi.org/10.1038/nature06258

@article{75e98b77a7d34f0696e5f8bba93e389f,

title = "A second generation human haplotype map of over 3.1 million SNPs",

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.",

author = "Frazer, {Kelly A.} and Ballinger, {Dennis G.} and Cox, {David R.} and Hinds, {David A.} and Stuve, {Laura L.} and Gibbs, {Richard A.} and Belmont, {John W.} and Andrew Boudreau and Paul Hardenbol and Leal, {Suzanne M.} and Shiran Pasternak and Wheeler, {David A.} and Willis, {Thomas D.} and Fuli Yu and Huanming Yang and Changqing Zeng and Yang Gao and Haoran Hu and Weitao Hu and Chaohua Li and Wei Lin and Siqi Liu and Hao Pan and Xiaoli Tang and Jian Wang and Wei Wang and Jun Yu and Bo Zhang and Qingrun Zhang and Hongbin Zhao and Hui Zhao and Jun Zhou and Gabriel, {Stacey B.} and Rachel Barry and Brendan Blumenstiel and Amy Camargo and Matthew Defelice and Maura Faggart and Mary Goyette and Supriya Gupta and Jamie Moore and Huy Nguyen and Onofrio, {Robert C.} and Melissa Parkin and Jessica Roy and Erich Stahl and Ellen Winchester and Liuda Ziaugra and David Altshuler and Yan Shen and Zhijian Yao and Wei Huang and Xun Chu and Yungang He and Li Jin and Yangfan Liu and Yayun Shen and Weiwei Sun and Haifeng Wang and Yi Wang and Ying Wang and Xiaoyan Xiong and Liang Xu and Waye, {Mary M.Y.} and Tsui, {Stephen K.W.} and Hong Xue and Wong, {J. Tze Fei} and Galver, {Luana M.} and Fan, {Jian Bing} and Kevin Gunderson and Murray, {Sarah S.} and Oliphant, {Arnold R.} and Chee, {Mark S.} and Alexandre Montpetit and Fanny Chagnon and Vincent Ferretti and Martin Leboeuf and Olivier, {Jean Fran{\c c}ois} and Phillips, {Michael S.} and St{\'e}phanie Roumy and Cl{\'e}mentine Sall{\'e}e and Andrei Verner and Hudson, {Thomas J.} and Kwok, {Pui Yan} and Dongmei Cai and Koboldt, {Daniel C.} and Miller, {Raymond D.} and Ludmila Pawlikowska and Patricia Taillon-Miller and Ming Xiao and Tsui, {Lap Chee} and William Mak and You, {Qiang Song} and Tam, {Paul K.H.} and Yusuke Nakamura and Takahisa Kawaguchi and Takuya Kitamoto and Takashi Morizono and Atsushi Nagashima and Yozo Ohnishi and Akihiro Sekine and Toshihiro Tanaka and Tatsuhiko Tsunoda and Panos Deloukas and Bird, {Christine P.} and Marcos Delgado and Dermitzakis, {Emmanouil T.} and Rhian Gwilliam and Sarah Hunt and Jonathan Morrison and Don Powell and Stranger, {Barbara E.} and Pamela Whittaker and Bentley, {David R.} and Daly, {Mark J.} and {De Bakker}, {Paul I.W.} and Jeff Barrett and Chretien, {Yves R.} and Julian Maller and Steve McCarroll and Nick Patterson and Itsik Pe'Er and Alkes Price and Shaun Purcell and Richter, {Daniel J.} and Pardis Sabeti and Richa Saxena and Schaffner, {Stephen F.} and Sham, {Pak C.} and Patrick Varilly and Stein, {Lincoln D.} and Lalitha Krishnan and Smith, {Albert Vernon} and Tello-Ruiz, {Marcela K.} and Thorisson, {Gudmundur A.} and Aravinda Chakravarti and Chen, {Peter E.} and Cutler, {David J.} and Kashuk, {Carl S.} and Shin Lin and Abecasis, {Gon{\c c}alo R.} and Weihua Guan and Yun Li and Munro, {Heather M.} and Qin, {Zhaohui Steve} and Thomas, {Daryl J.} and Gilean McVean and Adam Auton and Leonardo Bottolo and Niall Cardin and Susana Eyheramendy and Colin Freeman and Jonathan Marchini and Simon Myers and Chris Spencer and Matthew Stephens and Peter Donnelly and Cardon, {Lon R.} and Geraldine Clarke and Evans, {David M.} and Morris, {Andrew P.} and Weir, {Bruce S.} and Johnson, {Todd A.} and Mullikin, {James C.} and Sherry, {Stephen T.} and Michael Feolo and Andrew Skol and Houcan Zhang and Ichiro Matsuda and Yoshimitsu Fukushima and MacEr, {Darryl R.} and Eiko Suda and Rotimi, {Charles N.} and Adebamowo, {Clement A.} and Ike Ajayi and Toyin Aniagwu and Marshall, {Patricia A.} and Chibuzor Nkwodimmah and Royal, {Charmaine D.M.} and Leppert, {Mark F.} and Missy Dixon and Andy Peiffer and Renzong Qiu and Alastair Kent and Kazuto Kato and Norio Niikawa and Adewole, {Isaac F.} and Knoppers, {Bartha M.} and Foster, {Morris W.} and Clayton, {Ellen Wright} and Jessica Watkin and Donna Muzny and Lynne Nazareth and Erica Sodergren and Weinstock, {George M.} and Imtaz Yakub and Birren, {Bruce W.} and Wilson, {Richard K.} and Fulton, {Lucinda L.} and Jane Rogers and John Burton and Carter, {Nigel P.} and Clee, {Christopher M.} and Mark Griffiths and Jones, {Matthew C.} and Kirsten McLay and Plumb, {Robert W.} and Ross, {Mark T.} and Sims, {Sarah K.} and Willey, {David L.} and Zhu Chen and Hua Han and Le Kang and Martin Godbout and Wallenburg, {John C.} and Paul L'Archev{\^e}que and Guy Bellemare and Koji Saeki and Hongguang Wang and Daochang An and Hongbo Fu and Qing Li and Zhen Wang and Renwu Wang and Holden, {Arthur L.} and Brooks, {Lisa D.} and McEwen, {Jean E.} and Guyer, {Mark S.} and Wang, {Vivian Ota} and Peterson, {Jane L.} and Michael Shi and Jack Spiegel and Sung, {Lawrence M.} and Zacharia, {Lynn F.} and Collins, {Francis S.} and Karen Kennedy and Ruth Jamieson and John Stewart",

note = "Funding Information: Acknowledgements We thank many people who contributed to this project: all members of the genotyping laboratory and the sample, primer, bioinformatics, data quality and IT groups at Perlegen Sciences for technical and infrastructural support; J. Beck, C. Beiswanger, D. Coppock, A. Leach, J. Mintzer and L. Toji for transforming the Yoruba, Japanese and Han Chinese samples, distributing the DNA and cell lines, storing the samples for use in future research, and producing the community newsletters and reports; J. Greenberg and R. Anderson for providing funding and support for cell line transformation and storage in the NIGMS Human Genetic Cell Repository at the Coriell Institute; T. Dibling, T. Ishikura, S. Kanazawa, S. Mizusawa and S. Saito for help with genotyping; C. Hind and A. Moghadam for technical support in genotyping and all members of the subcloning and sequencing teams at the Wellcome Trust Sanger Institute; X. Ke for help with data analysis; Oxford E-Science Centre for provision of high-performance computing resources; H. Chen, W. Chen, L. Deng, Y. Dong, C. Fu, L. Gao, H. Geng, J. Geng, M. He, H. Li, H. Li, S. Li, X. Li, B. Liu, Z. Liu, F. Lu, F. Lu, G. Lu, C. Luo, X. Wang, Z. Wang, C. Ye and X. Yu for help with genotyping and sample collection; X. Feng, Y. Li, J. Ren and X. Zhou for help with sample collection; J. Fan, W. Gu, W. Guan, S. Hu, H. Jiang, R. Lei, Y. Lin, Z. Niu, B. Wang, L. Yang, W. Yang, Y. Wang, Z. Wang, S. Xu, W. Yan, H. Yang, W. Yuan, C. Zhang, J. Zhang, K. Zhang and G. Zhao for help with genotyping; P. Fong, C. Lai, C. Lau, T. Leung, L. Luk and W. Tong for help with genotyping; C. Pang for help with genotyping; K. Ding, B. Qiang, J. Zhang, X. Zhang and K. Zhou for help with genotyping; Q. Fu, S. Ghose, X. Lu, D. Nelson, A. Perez, S. Poole, R. Vega and H. Yonath for help with genotyping; C. Bruckner, T. Brundage, S. Chow, O. Iartchouk, M. Jain, M. Moorhead and K. Tran for help with genotyping; N. Addleman, J. Atilano, T. Chan, C. Chu, C. Ha, T. Nguyen, M. Minton and A. Phong for help with genotyping, and D. Lind for help with quality control and experimental design; R. Donaldson and S. Duan for help with genotyping, and J. Rice and N. Saccone for help with experimental design; J. Wigginton for help with implementing and testing QA/QC software; A. Clark, B. Keats, R. Myers, D. Nickerson and A. Williamson for providing advice to NIH; C. Juenger, C. Bennet, C. Bird, J. Melone, P. Nailer, M. Weiss, J. Witonsky and E. DeHaut-Combs for help with project management; M. Gray for organizing phone calls and meetings; D. Leja for help with figures; the Yoruba people of Ibadan, Nigeria, the people of Tokyo, Japan, and the community at Beijing Normal University, who participated in public consultations and community engagements; the people in these communities who donated their blood samples; and the people in the Utah CEPH community who allowed the samples they donated earlier to be used for the Project. This work was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology, the Wellcome Trust, Nuffield Trust, Wolfson Foundation, UK EPSRC, Genome Canada, G{\'e}nome Qu{\'e}bec, the Chinese Academy of Sciences, the Ministry of Science and Technology of the People{\textquoteright}s Republic of China, the National Natural Science Foundation of China, the Hong Kong Innovation and Technology Commission, the University Grants Committee of Hong Kong, the SNP Consortium, the US National Institutes of Health (FIC, NCI, NCRR, NEI, NHGRI, NIA, NIAAA, NIAID, NIAMS, NIBIB, NIDA, NIDCD, NIDCR, NIDDK, NIEHS, NIGMS, NIMH, NINDS, NLM, OD), the W.M. Keck Foundation, and the Delores DoreEcclesFoundation.AllSNPsgenotypedwithintheHapMapProject are available from dbSNP (http://www.ncbi.nlm.nih.gov/SNP); all genotype information is available from dbSNP and the HapMap website (http://www.hapmap.org).",

year = "2007",

month = oct,

day = "18",

doi = "10.1038/nature06258",

language = "English (US)",

volume = "449",

pages = "851--861",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7164",

}

TY - JOUR

T1 - A second generation human haplotype map of over 3.1 million SNPs

AU - Frazer, Kelly A.

AU - Ballinger, Dennis G.

AU - Cox, David R.

AU - Hinds, David A.

AU - Stuve, Laura L.

AU - Gibbs, Richard A.

AU - Belmont, John W.

AU - Boudreau, Andrew

AU - Hardenbol, Paul

AU - Leal, Suzanne M.

AU - Pasternak, Shiran

AU - Wheeler, David A.

AU - Willis, Thomas D.

AU - Yu, Fuli

AU - Yang, Huanming

AU - Zeng, Changqing

AU - Gao, Yang

AU - Hu, Haoran

AU - Hu, Weitao

AU - Li, Chaohua

AU - Lin, Wei

AU - Liu, Siqi

AU - Pan, Hao

AU - Tang, Xiaoli

AU - Wang, Jian

AU - Wang, Wei

AU - Yu, Jun

AU - Zhang, Bo

AU - Zhang, Qingrun

AU - Zhao, Hongbin

AU - Zhao, Hui

AU - Zhou, Jun

AU - Gabriel, Stacey B.

AU - Barry, Rachel

AU - Blumenstiel, Brendan

AU - Camargo, Amy

AU - Defelice, Matthew

AU - Faggart, Maura

AU - Goyette, Mary

AU - Gupta, Supriya

AU - Moore, Jamie

AU - Nguyen, Huy

AU - Onofrio, Robert C.

AU - Parkin, Melissa

AU - Roy, Jessica

AU - Stahl, Erich

AU - Winchester, Ellen

AU - Ziaugra, Liuda

AU - Altshuler, David

AU - Shen, Yan

AU - Yao, Zhijian

AU - Huang, Wei

AU - Chu, Xun

AU - He, Yungang

AU - Jin, Li

AU - Liu, Yangfan

AU - Shen, Yayun

AU - Sun, Weiwei

AU - Wang, Haifeng

AU - Wang, Yi

AU - Wang, Ying

AU - Xiong, Xiaoyan

AU - Xu, Liang

AU - Waye, Mary M.Y.

AU - Tsui, Stephen K.W.

AU - Xue, Hong

AU - Wong, J. Tze Fei

AU - Galver, Luana M.

AU - Fan, Jian Bing

AU - Gunderson, Kevin

AU - Murray, Sarah S.

AU - Oliphant, Arnold R.

AU - Chee, Mark S.

AU - Montpetit, Alexandre

AU - Chagnon, Fanny

AU - Ferretti, Vincent

AU - Leboeuf, Martin

AU - Olivier, Jean François

AU - Phillips, Michael S.

AU - Roumy, Stéphanie

AU - Sallée, Clémentine

AU - Verner, Andrei

AU - Hudson, Thomas J.

AU - Kwok, Pui Yan

AU - Cai, Dongmei

AU - Koboldt, Daniel C.

AU - Miller, Raymond D.

AU - Pawlikowska, Ludmila

AU - Taillon-Miller, Patricia

AU - Xiao, Ming

AU - Tsui, Lap Chee

AU - Mak, William

AU - You, Qiang Song

AU - Tam, Paul K.H.

AU - Nakamura, Yusuke

AU - Kawaguchi, Takahisa

AU - Kitamoto, Takuya

AU - Morizono, Takashi

AU - Nagashima, Atsushi

AU - Ohnishi, Yozo

AU - Sekine, Akihiro

AU - Tanaka, Toshihiro

AU - Tsunoda, Tatsuhiko

AU - Deloukas, Panos

AU - Bird, Christine P.

AU - Delgado, Marcos

AU - Dermitzakis, Emmanouil T.

AU - Gwilliam, Rhian

AU - Hunt, Sarah

AU - Morrison, Jonathan

AU - Powell, Don

AU - Stranger, Barbara E.

AU - Whittaker, Pamela

AU - Bentley, David R.

AU - Daly, Mark J.

AU - De Bakker, Paul I.W.

AU - Barrett, Jeff

AU - Chretien, Yves R.

AU - Maller, Julian

AU - McCarroll, Steve

AU - Patterson, Nick

AU - Pe'Er, Itsik

AU - Price, Alkes

AU - Purcell, Shaun

AU - Richter, Daniel J.

AU - Sabeti, Pardis

AU - Saxena, Richa

AU - Schaffner, Stephen F.

AU - Sham, Pak C.

AU - Varilly, Patrick

AU - Stein, Lincoln D.

AU - Krishnan, Lalitha

AU - Smith, Albert Vernon

AU - Tello-Ruiz, Marcela K.

AU - Thorisson, Gudmundur A.

AU - Chakravarti, Aravinda

AU - Chen, Peter E.

AU - Cutler, David J.

AU - Kashuk, Carl S.

AU - Lin, Shin

AU - Abecasis, Gonçalo R.

AU - Guan, Weihua

AU - Li, Yun

AU - Munro, Heather M.

AU - Qin, Zhaohui Steve

AU - Thomas, Daryl J.

AU - McVean, Gilean

AU - Auton, Adam

AU - Bottolo, Leonardo

AU - Cardin, Niall

AU - Eyheramendy, Susana

AU - Freeman, Colin

AU - Marchini, Jonathan

AU - Myers, Simon

AU - Spencer, Chris

AU - Stephens, Matthew

AU - Donnelly, Peter

AU - Cardon, Lon R.

AU - Clarke, Geraldine

AU - Evans, David M.

AU - Morris, Andrew P.

AU - Weir, Bruce S.

AU - Johnson, Todd A.

AU - Mullikin, James C.

AU - Sherry, Stephen T.

AU - Feolo, Michael

AU - Skol, Andrew

AU - Zhang, Houcan

AU - Matsuda, Ichiro

AU - Fukushima, Yoshimitsu

AU - MacEr, Darryl R.

AU - Suda, Eiko

AU - Rotimi, Charles N.

AU - Adebamowo, Clement A.

AU - Ajayi, Ike

AU - Aniagwu, Toyin

AU - Marshall, Patricia A.

AU - Nkwodimmah, Chibuzor

AU - Royal, Charmaine D.M.

AU - Leppert, Mark F.

AU - Dixon, Missy

AU - Peiffer, Andy

AU - Qiu, Renzong

AU - Kent, Alastair

AU - Kato, Kazuto

AU - Niikawa, Norio

AU - Adewole, Isaac F.

AU - Knoppers, Bartha M.

AU - Foster, Morris W.

AU - Clayton, Ellen Wright

AU - Watkin, Jessica

AU - Muzny, Donna

AU - Nazareth, Lynne

AU - Sodergren, Erica

AU - Weinstock, George M.

AU - Yakub, Imtaz

AU - Birren, Bruce W.

AU - Wilson, Richard K.

AU - Fulton, Lucinda L.

AU - Rogers, Jane

AU - Burton, John

AU - Carter, Nigel P.

AU - Clee, Christopher M.

AU - Griffiths, Mark

AU - Jones, Matthew C.

AU - McLay, Kirsten

AU - Plumb, Robert W.

AU - Ross, Mark T.

AU - Sims, Sarah K.

AU - Willey, David L.

AU - Chen, Zhu

AU - Han, Hua

AU - Kang, Le

AU - Godbout, Martin

AU - Wallenburg, John C.

AU - L'Archevêque, Paul

AU - Bellemare, Guy

AU - Saeki, Koji

AU - Wang, Hongguang

AU - An, Daochang

AU - Fu, Hongbo

AU - Li, Qing

AU - Wang, Zhen

AU - Wang, Renwu

AU - Holden, Arthur L.

AU - Brooks, Lisa D.

AU - McEwen, Jean E.

AU - Guyer, Mark S.

AU - Wang, Vivian Ota

AU - Peterson, Jane L.

AU - Shi, Michael

AU - Spiegel, Jack

AU - Sung, Lawrence M.

AU - Zacharia, Lynn F.

AU - Collins, Francis S.

AU - Kennedy, Karen

AU - Jamieson, Ruth

AU - Stewart, John

N1 - Funding Information: Acknowledgements We thank many people who contributed to this project: all members of the genotyping laboratory and the sample, primer, bioinformatics, data quality and IT groups at Perlegen Sciences for technical and infrastructural support; J. Beck, C. Beiswanger, D. Coppock, A. Leach, J. Mintzer and L. Toji for transforming the Yoruba, Japanese and Han Chinese samples, distributing the DNA and cell lines, storing the samples for use in future research, and producing the community newsletters and reports; J. Greenberg and R. Anderson for providing funding and support for cell line transformation and storage in the NIGMS Human Genetic Cell Repository at the Coriell Institute; T. Dibling, T. Ishikura, S. Kanazawa, S. Mizusawa and S. Saito for help with genotyping; C. Hind and A. Moghadam for technical support in genotyping and all members of the subcloning and sequencing teams at the Wellcome Trust Sanger Institute; X. Ke for help with data analysis; Oxford E-Science Centre for provision of high-performance computing resources; H. Chen, W. Chen, L. Deng, Y. Dong, C. Fu, L. Gao, H. Geng, J. Geng, M. He, H. Li, H. Li, S. Li, X. Li, B. Liu, Z. Liu, F. Lu, F. Lu, G. Lu, C. Luo, X. Wang, Z. Wang, C. Ye and X. Yu for help with genotyping and sample collection; X. Feng, Y. Li, J. Ren and X. Zhou for help with sample collection; J. Fan, W. Gu, W. Guan, S. Hu, H. Jiang, R. Lei, Y. Lin, Z. Niu, B. Wang, L. Yang, W. Yang, Y. Wang, Z. Wang, S. Xu, W. Yan, H. Yang, W. Yuan, C. Zhang, J. Zhang, K. Zhang and G. Zhao for help with genotyping; P. Fong, C. Lai, C. Lau, T. Leung, L. Luk and W. Tong for help with genotyping; C. Pang for help with genotyping; K. Ding, B. Qiang, J. Zhang, X. Zhang and K. Zhou for help with genotyping; Q. Fu, S. Ghose, X. Lu, D. Nelson, A. Perez, S. Poole, R. Vega and H. Yonath for help with genotyping; C. Bruckner, T. Brundage, S. Chow, O. Iartchouk, M. Jain, M. Moorhead and K. Tran for help with genotyping; N. Addleman, J. Atilano, T. Chan, C. Chu, C. Ha, T. Nguyen, M. Minton and A. Phong for help with genotyping, and D. Lind for help with quality control and experimental design; R. Donaldson and S. Duan for help with genotyping, and J. Rice and N. Saccone for help with experimental design; J. Wigginton for help with implementing and testing QA/QC software; A. Clark, B. Keats, R. Myers, D. Nickerson and A. Williamson for providing advice to NIH; C. Juenger, C. Bennet, C. Bird, J. Melone, P. Nailer, M. Weiss, J. Witonsky and E. DeHaut-Combs for help with project management; M. Gray for organizing phone calls and meetings; D. Leja for help with figures; the Yoruba people of Ibadan, Nigeria, the people of Tokyo, Japan, and the community at Beijing Normal University, who participated in public consultations and community engagements; the people in these communities who donated their blood samples; and the people in the Utah CEPH community who allowed the samples they donated earlier to be used for the Project. This work was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology, the Wellcome Trust, Nuffield Trust, Wolfson Foundation, UK EPSRC, Genome Canada, Génome Québec, the Chinese Academy of Sciences, the Ministry of Science and Technology of the People’s Republic of China, the National Natural Science Foundation of China, the Hong Kong Innovation and Technology Commission, the University Grants Committee of Hong Kong, the SNP Consortium, the US National Institutes of Health (FIC, NCI, NCRR, NEI, NHGRI, NIA, NIAAA, NIAID, NIAMS, NIBIB, NIDA, NIDCD, NIDCR, NIDDK, NIEHS, NIGMS, NIMH, NINDS, NLM, OD), the W.M. Keck Foundation, and the Delores DoreEcclesFoundation.AllSNPsgenotypedwithintheHapMapProject are available from dbSNP (http://www.ncbi.nlm.nih.gov/SNP); all genotype information is available from dbSNP and the HapMap website (http://www.hapmap.org).

PY - 2007/10/18

Y1 - 2007/10/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=35348983887&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35348983887&partnerID=8YFLogxK

U2 - 10.1038/nature06258

DO - 10.1038/nature06258

M3 - Article

C2 - 17943122

AN - SCOPUS:35348983887

SN - 0028-0836

VL - 449

SP - 851

EP - 861

JO - Nature

JF - Nature

IS - 7164

ER -

A second generation human haplotype map of over 3.1 million SNPs

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