Portal de Periódicos da CAPES

A second generation human haplotype map of over 3.1 million SNPs

2007; Nature Portfolio; Volume: 449; Issue: 7164 Linguagem: Inglês

10.1038/nature06258

1476-4687

Kelly A. Frazer, Dennis G. Ballinger, David R. Cox, David A. Hinds, Laura L. Stuvé, Richard A. Gibbs, John W. Belmont, Andrew Boudreau, Paul Hardenbol, Suzanne M. Leal, Shiran Pasternak, David A. Wheeler, T. 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 Gabriel, Rachel Barry, Brendan Blumenstiel, Amy L. 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, Jin Li, Yangfan Liu, Yayun Shen, Weiwei Sun, Haifeng Wang, Yi Wang, Ying Wang, Xiaoyan Xiong, Liang Xu, Mary Miu Yee Waye, Stephen Kwok‐Wing Tsui, Hong Xue, J. Tze‐Fei Wong, Luana Galver, Jian-Bing Fan, Kevin L. Gunderson, Sarah S. Murray, Arnold Oliphant, Mark S. Chee, Alexandre Montpetit, Fanny Chagnon, Vincent Ferretti, Martin Leboeuf, Jean François Olivier, Michael 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, You‐Qiang Song, Paul Kwong Hang Tam, Yusuke Nakamura, Takahisa Kawaguchi, Takuya Kitamoto, Takashi Morizono, Atsushi Nagashima, Yozo Ohnishi, Akihiro Sekine, Toshihiro Tanaka, Tatsuhiko Tsunoda, Panos Deloukas, Christine Bird, Marcos Delgado, Emmanouil T. Dermitzakis, Rhian Gwilliam, Sarah Hunt, Jonathan J. Morrison, Don Powell, Barbara E. Stranger, Pamela Whittaker, David Bentley, Mark J. Daly, Paul I. W. de Bakker, Jeff Barrett, Yves Chrétien, Julian Maller, Steve McCarroll, Hon‐Cheong So, Itsik Pe’er, Alkes L. Price, Shaun Purcell, Daniel J. Richter, Pardis C. Sabeti, Richa Saxena, S. F. Schaffner, Pak C. Sham, Patrick Varilly, Lincoln D. Stein, Lalitha Krishnan, Albert V. Smith, Marcela K. Tello-Ruiz, Guðmundur Á. Þórisson, Aravinda Chakravarti, Peter E. Chen, David J. Cutler, Carl Kashuk, Shin Lin, Gonçalo R. Abecasis, Weihua Guan, Yun Li, Heather M. Munro, Zhaohui Qin, Daryl J. Thomas, Gil McVean, Adam Auton, Leonardo Bottolo, Niall J. Cardin, S. Eyheramendy, Colin Freeman, Jonathan Marchini, Simon Myers, Chris Spencer, Matthew Stephens, Peter Donnelly, Lon R. Cardon, Geraldine M Clarke, David M. Evans, Andrew P. Morris, Bruce S. Weir, Todd A. Johnson, James C. Mullikin, Stephen T. Sherry, Michael Feolo, Andrew D. Skol, Houcan Zhang, Ichiro Matsuda, Yoshimitsu Fukushima, Darryl Macer, Eiko Suda, Charles N. Rotimi, Clement Adebamowo, IkeOluwapo O. Ajayi, Toyin Aniagwu, Patricia A. Marshall, Chibuzor Nkwodimmah, Charmaine Royal, Mark Leppert, Missy Dixon, Andy Peiffer, Renzong Qiu, Alastair Kent, Yoshihiro Kato, Norio Niikawa, Isaac F. Adewole, Bartha Maria Knoppers, Morris W. Foster, Ellen Wright Clayton, Jessica Watkin, Donna M. Muzny, Lynne Nazareth, Erica Sodergren, George M. Weinstock, Imtaz Yakub, Bruce W. Birren, Richard K. Wilson, Lucinda Fulton, Jane Rogers, John H. Burton, Nigel P. Carter, Christopher M. Clee, Mark Griffiths, Matthew Jones, Kirsten McLay, R. 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, K. 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,

Genetic Mapping and Diversity in Plants and Animals

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. The International HapMap Consortium has produced a second-generation version of its remarkable haplotype map of the human genome. The Phase II HapMap charts human genetic variation even more extensively than the original, tripling of the number of genetic markers included. The original HapMap was instrumental in making large-scale genome-wide association studies possible. An indication of how this type of work will be extended with 'HapMap2' is presented in this issue: Sabeti et al. build on previous work detecting signs of positive natural selection on human genes. With many more markers now available, they have discovered three examples of apparent population-specific selection based on geographic area — involving gene pairs linked to Lassa virus in West Africa, skin pigmentation in Europe and hair follicle development in Asia — and they speculate on how these may relate to human biology. A consortium reports the tripling of the number of genetic markers in Phase II of the International HapMap Project. This map of human genetic variation will continue to revolutionize discovery of susceptibility loci in common genetic diseases, and study of genes under selection in humans.