%0 Journal Article %J Nature %D 2010 %T Integrating common and rare genetic variation in diverse human populations. %A Altshuler, David M %A Gibbs, Richard A %A Peltonen, Leena %A Altshuler, David M %A Gibbs, Richard A %A Peltonen, Leena %A Dermitzakis, Emmanouil %A Schaffner, Stephen F %A Yu, Fuli %A Peltonen, Leena %A Dermitzakis, Emmanouil %A Bonnen, Penelope E %A Altshuler, David M %A Gibbs, Richard A %A de Bakker, Paul I W %A Deloukas, Panos %A Gabriel, Stacey B %A Gwilliam, Rhian %A Hunt, Sarah %A Inouye, Michael %A Jia, Xiaoming %A Palotie, Aarno %A Parkin, Melissa %A Whittaker, Pamela %A Yu, Fuli %A Chang, Kyle %A Hawes, Alicia %A Lewis, Lora R %A Ren, Yanru %A Wheeler, David %A Gibbs, Richard A %A Muzny, Donna Marie %A Barnes, Chris %A Darvishi, Katayoon %A Hurles, Matthew %A Korn, Joshua M %A Kristiansson, Kati %A Lee, Charles %A McCarrol, Steven A %A Nemesh, James %A Dermitzakis, Emmanouil %A Keinan, Alon %A Montgomery, Stephen B %A Pollack, Samuela %A Price, Alkes L %A Soranzo, Nicole %A Bonnen, Penelope E %A Gibbs, Richard A %A Gonzaga-Jauregui, Claudia %A Keinan, Alon %A Price, Alkes L %A Yu, Fuli %A Anttila, Verneri %A Brodeur, Wendy %A Daly, Mark J %A Leslie, Stephen %A McVean, Gil %A Moutsianas, Loukas %A Nguyen, Huy %A Schaffner, Stephen F %A Zhang, Qingrun %A Ghori, Mohammed J R %A McGinnis, Ralph %A McLaren, William %A Pollack, Samuela %A Price, Alkes L %A Schaffner, Stephen F %A Takeuchi, Fumihiko %A Grossman, Sharon R %A Shlyakhter, Ilya %A Hostetter, Elizabeth B %A Sabeti, Pardis C %A Adebamowo, Clement A %A Foster, Morris W %A Gordon, Deborah R %A Licinio, Julio %A Manca, Maria Cristina %A Marshall, Patricia A %A Matsuda, Ichiro %A Ngare, Duncan %A Wang, Vivian Ota %A Reddy, Deepa %A Rotimi, Charles N %A Royal, Charmaine D %A Sharp, Richard R %A Zeng, Changqing %A Brooks, Lisa D %A McEwen, Jean E %K DNA Copy Number Variations %K Genome, Human %K Human Genome Project %K Humans %K Polymorphism, Single Nucleotide %K Population Groups %X

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of %B Nature %V 467 %P 52-8 %8 2010 Sep 02 %G eng %N 7311 %1 https://www.ncbi.nlm.nih.gov/pubmed/20811451?dopt=Abstract %R 10.1038/nature09298 %0 Journal Article %J Nature %D 2007 %T Genome-wide detection and characterization of positive selection in human populations. %A Sabeti, Pardis C %A Varilly, Patrick %A Fry, Ben %A Lohmueller, Jason %A Hostetter, Elizabeth %A Cotsapas, Chris %A Xie, Xiaohui %A Byrne, Elizabeth H %A McCarroll, Steven A %A Gaudet, Rachelle %A Schaffner, Stephen F %A Lander, Eric S %A Frazer, Kelly A %A Ballinger, Dennis G %A Cox, David R %A Hinds, David A %A Stuve, Laura L %A Gibbs, Richard A %A Belmont, John W %A Boudreau, Andrew %A Hardenbol, Paul %A Leal, Suzanne M %A Pasternak, Shiran %A Wheeler, David A %A Willis, Thomas D %A Yu, Fuli %A Yang, Huanming %A Zeng, Changqing %A Gao, Yang %A Hu, Haoran %A Hu, Weitao %A Li, Chaohua %A Lin, Wei %A Liu, Siqi %A Pan, Hao %A Tang, Xiaoli %A Wang, Jian %A Wang, Wei %A Yu, Jun %A Zhang, Bo %A Zhang, Qingrun %A Zhao, Hongbin %A Zhao, Hui %A Zhou, Jun %A Gabriel, Stacey B %A Barry, Rachel %A Blumenstiel, Brendan %A Camargo, Amy %A Defelice, Matthew %A Faggart, Maura %A Goyette, Mary %A Gupta, Supriya %A Moore, Jamie %A Nguyen, Huy %A Onofrio, Robert C %A Parkin, Melissa %A Roy, Jessica %A Stahl, Erich %A Winchester, Ellen %A Ziaugra, Liuda %A Altshuler, David %A Shen, Yan %A Yao, Zhijian %A Huang, Wei %A Chu, Xun %A He, Yungang %A Jin, Li %A Liu, Yangfan %A Shen, Yayun %A Sun, Weiwei %A Wang, Haifeng %A Wang, Yi %A Wang, Ying %A Xiong, Xiaoyan %A Xu, Liang %A Waye, Mary M Y %A Tsui, Stephen K W %A Xue, Hong %A Wong, J Tze-Fei %A Galver, Luana M %A Fan, Jian-Bing %A Gunderson, Kevin %A Murray, Sarah S %A Oliphant, Arnold R %A Chee, Mark S %A Montpetit, Alexandre %A Chagnon, Fanny %A Ferretti, Vincent %A Leboeuf, Martin %A Olivier, Jean-François %A Phillips, Michael S %A Roumy, Stéphanie %A Sallée, Clémentine %A Verner, Andrei %A Hudson, Thomas J %A Kwok, Pui-Yan %A Cai, Dongmei %A Koboldt, Daniel C %A Miller, Raymond D %A Pawlikowska, Ludmila %A Taillon-Miller, Patricia %A Xiao, Ming %A Tsui, Lap-Chee %A Mak, William %A Song, You Qiang %A Tam, Paul K H %A Nakamura, Yusuke %A Kawaguchi, Takahisa %A Kitamoto, Takuya %A Morizono, Takashi %A Nagashima, Atsushi %A Ohnishi, Yozo %A Sekine, Akihiro %A Tanaka, Toshihiro %A Tsunoda, Tatsuhiko %A Deloukas, Panos %A Bird, Christine P %A Delgado, Marcos %A Dermitzakis, Emmanouil T %A Gwilliam, Rhian %A Hunt, Sarah %A Morrison, Jonathan %A Powell, Don %A Stranger, Barbara E %A Whittaker, Pamela %A Bentley, David R %A Daly, Mark J %A de Bakker, Paul I W %A Barrett, Jeff %A Chretien, Yves R %A Maller, Julian %A McCarroll, Steve %A Patterson, Nick %A Pe'er, Itsik %A Price, Alkes %A Purcell, Shaun %A Richter, Daniel J %A Sabeti, Pardis %A Saxena, Richa %A Schaffner, Stephen F %A Sham, Pak C %A Varilly, Patrick %A Altshuler, David %A Stein, Lincoln D %A Krishnan, Lalitha %A Smith, Albert Vernon %A Tello-Ruiz, Marcela K %A Thorisson, Gudmundur A %A Chakravarti, Aravinda %A Chen, Peter E %A Cutler, David J %A Kashuk, Carl S %A Lin, Shin %A Abecasis, Gonçalo R %A Guan, Weihua %A Li, Yun %A Munro, Heather M %A Qin, Zhaohui Steve %A Thomas, Daryl J %A McVean, Gilean %A Auton, Adam %A Bottolo, Leonardo %A Cardin, Niall %A Eyheramendy, Susana %A Freeman, Colin %A Marchini, Jonathan %A Myers, Simon %A Spencer, Chris %A Stephens, Matthew %A Donnelly, Peter %A Cardon, Lon R %A Clarke, Geraldine %A Evans, David M %A Morris, Andrew P %A Weir, Bruce S %A Tsunoda, Tatsuhiko %A Johnson, Todd A %A Mullikin, James C %A Sherry, Stephen T %A Feolo, Michael %A Skol, Andrew %A Zhang, Houcan %A Zeng, Changqing %A Zhao, Hui %A Matsuda, Ichiro %A Fukushima, Yoshimitsu %A Macer, Darryl R %A Suda, Eiko %A Rotimi, Charles N %A Adebamowo, Clement A %A Ajayi, Ike %A Aniagwu, Toyin %A Marshall, Patricia A %A Nkwodimmah, Chibuzor %A Royal, Charmaine D M %A Leppert, Mark F %A Dixon, Missy %A Peiffer, Andy %A Qiu, Renzong %A Kent, Alastair %A Kato, Kazuto %A Niikawa, Norio %A Adewole, Isaac F %A Knoppers, Bartha M %A Foster, Morris W %A Clayton, Ellen Wright %A Watkin, Jessica %A Gibbs, Richard A %A Belmont, John W %A Muzny, Donna %A Nazareth, Lynne %A Sodergren, Erica %A Weinstock, George M %A Wheeler, David A %A Yakub, Imtaz %A Gabriel, Stacey B %A Onofrio, Robert C %A Richter, Daniel J %A Ziaugra, Liuda %A Birren, Bruce W %A Daly, Mark J %A Altshuler, David %A Wilson, Richard K %A Fulton, Lucinda L %A Rogers, Jane %A Burton, John %A Carter, Nigel P %A Clee, Christopher M %A Griffiths, Mark %A Jones, Matthew C %A McLay, Kirsten %A Plumb, Robert W %A Ross, Mark T %A Sims, Sarah K %A Willey, David L %A Chen, Zhu %A Han, Hua %A Kang, Le %A Godbout, Martin %A Wallenburg, John C %A L'Archevêque, Paul %A Bellemare, Guy %A Saeki, Koji %A Wang, Hongguang %A An, Daochang %A Fu, Hongbo %A Li, Qing %A Wang, Zhen %A Wang, Renwu %A Holden, Arthur L %A Brooks, Lisa D %A McEwen, Jean E %A Guyer, Mark S %A Wang, Vivian Ota %A Peterson, Jane L %A Shi, Michael %A Spiegel, Jack %A Sung, Lawrence M %A Zacharia, Lynn F %A Collins, Francis S %A Kennedy, Karen %A Jamieson, Ruth %A Stewart, John %K Antiporters %K Edar Receptor %K Gene Frequency %K Genetics, Population %K Genome, Human %K Geography %K Haplotypes %K Humans %K Models, Molecular %K Polymorphism, Single Nucleotide %K Protein Structure, Tertiary %K Selection, Genetic %X

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.

%B Nature %V 449 %P 913-8 %8 2007 Oct 18 %G eng %N 7164 %1 https://www.ncbi.nlm.nih.gov/pubmed/17943131?dopt=Abstract %R 10.1038/nature06250 %0 Journal Article %J Nature %D 2007 %T A second generation human haplotype map of over 3.1 million SNPs. %A Frazer, Kelly A %A Ballinger, Dennis G %A Cox, David R %A Hinds, David A %A Stuve, Laura L %A Gibbs, Richard A %A Belmont, John W %A Boudreau, Andrew %A Hardenbol, Paul %A Leal, Suzanne M %A Pasternak, Shiran %A Wheeler, David A %A Willis, Thomas D %A Yu, Fuli %A Yang, Huanming %A Zeng, Changqing %A Gao, Yang %A Hu, Haoran %A Hu, Weitao %A Li, Chaohua %A Lin, Wei %A Liu, Siqi %A Pan, Hao %A Tang, Xiaoli %A Wang, Jian %A Wang, Wei %A Yu, Jun %A Zhang, Bo %A Zhang, Qingrun %A Zhao, Hongbin %A Zhao, Hui %A Zhou, Jun %A Gabriel, Stacey B %A Barry, Rachel %A Blumenstiel, Brendan %A Camargo, Amy %A Defelice, Matthew %A Faggart, Maura %A Goyette, Mary %A Gupta, Supriya %A Moore, Jamie %A Nguyen, Huy %A Onofrio, Robert C %A Parkin, Melissa %A Roy, Jessica %A Stahl, Erich %A Winchester, Ellen %A Ziaugra, Liuda %A Altshuler, David %A Shen, Yan %A Yao, Zhijian %A Huang, Wei %A Chu, Xun %A He, Yungang %A Jin, Li %A Liu, Yangfan %A Shen, Yayun %A Sun, Weiwei %A Wang, Haifeng %A Wang, Yi %A Wang, Ying %A Xiong, Xiaoyan %A Xu, Liang %A Waye, Mary M Y %A Tsui, Stephen K W %A Xue, Hong %A Wong, J Tze-Fei %A Galver, Luana M %A Fan, Jian-Bing %A Gunderson, Kevin %A Murray, Sarah S %A Oliphant, Arnold R %A Chee, Mark S %A Montpetit, Alexandre %A Chagnon, Fanny %A Ferretti, Vincent %A Leboeuf, Martin %A Olivier, Jean-François %A Phillips, Michael S %A Roumy, Stéphanie %A Sallée, Clémentine %A Verner, Andrei %A Hudson, Thomas J %A Kwok, Pui-Yan %A Cai, Dongmei %A Koboldt, Daniel C %A Miller, Raymond D %A Pawlikowska, Ludmila %A Taillon-Miller, Patricia %A Xiao, Ming %A Tsui, Lap-Chee %A Mak, William %A Song, You Qiang %A Tam, Paul K H %A Nakamura, Yusuke %A Kawaguchi, Takahisa %A Kitamoto, Takuya %A Morizono, Takashi %A Nagashima, Atsushi %A Ohnishi, Yozo %A Sekine, Akihiro %A Tanaka, Toshihiro %A Tsunoda, Tatsuhiko %A Deloukas, Panos %A Bird, Christine P %A Delgado, Marcos %A Dermitzakis, Emmanouil T %A Gwilliam, Rhian %A Hunt, Sarah %A Morrison, Jonathan %A Powell, Don %A Stranger, Barbara E %A Whittaker, Pamela %A Bentley, David R %A Daly, Mark J %A de Bakker, Paul I W %A Barrett, Jeff %A Chretien, Yves R %A Maller, Julian %A McCarroll, Steve %A Patterson, Nick %A Pe'er, Itsik %A Price, Alkes %A Purcell, Shaun %A Richter, Daniel J %A Sabeti, Pardis %A Saxena, Richa %A Schaffner, Stephen F %A Sham, Pak C %A Varilly, Patrick %A Altshuler, David %A Stein, Lincoln D %A Krishnan, Lalitha %A Smith, Albert Vernon %A Tello-Ruiz, Marcela K %A Thorisson, Gudmundur A %A Chakravarti, Aravinda %A Chen, Peter E %A Cutler, David J %A Kashuk, Carl S %A Lin, Shin %A Abecasis, Gonçalo R %A Guan, Weihua %A Li, Yun %A Munro, Heather M %A Qin, Zhaohui Steve %A Thomas, Daryl J %A McVean, Gilean %A Auton, Adam %A Bottolo, Leonardo %A Cardin, Niall %A Eyheramendy, Susana %A Freeman, Colin %A Marchini, Jonathan %A Myers, Simon %A Spencer, Chris %A Stephens, Matthew %A Donnelly, Peter %A Cardon, Lon R %A Clarke, Geraldine %A Evans, David M %A Morris, Andrew P %A Weir, Bruce S %A Tsunoda, Tatsuhiko %A Mullikin, James C %A Sherry, Stephen T %A Feolo, Michael %A Skol, Andrew %A Zhang, Houcan %A Zeng, Changqing %A Zhao, Hui %A Matsuda, Ichiro %A Fukushima, Yoshimitsu %A Macer, Darryl R %A Suda, Eiko %A Rotimi, Charles N %A Adebamowo, Clement A %A Ajayi, Ike %A Aniagwu, Toyin %A Marshall, Patricia A %A Nkwodimmah, Chibuzor %A Royal, Charmaine D M %A Leppert, Mark F %A Dixon, Missy %A Peiffer, Andy %A Qiu, Renzong %A Kent, Alastair %A Kato, Kazuto %A Niikawa, Norio %A Adewole, Isaac F %A Knoppers, Bartha M %A Foster, Morris W %A Clayton, Ellen Wright %A Watkin, Jessica %A Gibbs, Richard A %A Belmont, John W %A Muzny, Donna %A Nazareth, Lynne %A Sodergren, Erica %A Weinstock, George M %A Wheeler, David A %A Yakub, Imtaz %A Gabriel, Stacey B %A Onofrio, Robert C %A Richter, Daniel J %A Ziaugra, Liuda %A Birren, Bruce W %A Daly, Mark J %A Altshuler, David %A Wilson, Richard K %A Fulton, Lucinda L %A Rogers, Jane %A Burton, John %A Carter, Nigel P %A Clee, Christopher M %A Griffiths, Mark %A Jones, Matthew C %A McLay, Kirsten %A Plumb, Robert W %A Ross, Mark T %A Sims, Sarah K %A Willey, David L %A Chen, Zhu %A Han, Hua %A Kang, Le %A Godbout, Martin %A Wallenburg, John C %A L'Archevêque, Paul %A Bellemare, Guy %A Saeki, Koji %A Wang, Hongguang %A An, Daochang %A Fu, Hongbo %A Li, Qing %A Wang, Zhen %A Wang, Renwu %A Holden, Arthur L %A Brooks, Lisa D %A McEwen, Jean E %A Guyer, Mark S %A Wang, Vivian Ota %A Peterson, Jane L %A Shi, Michael %A Spiegel, Jack %A Sung, Lawrence M %A Zacharia, Lynn F %A Collins, Francis S %A Kennedy, Karen %A Jamieson, Ruth %A Stewart, John %K Female %K Haplotypes %K Homozygote %K Humans %K Linkage Disequilibrium %K Male %K Polymorphism, Single Nucleotide %K Racial Groups %K Recombination, Genetic %K Selection, Genetic %X

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.

%B Nature %V 449 %P 851-61 %8 2007 Oct 18 %G eng %N 7164 %1 https://www.ncbi.nlm.nih.gov/pubmed/17943122?dopt=Abstract %R 10.1038/nature06258