An integrated map of genetic variation from 1,092 human genomes.
The 1000 Genomes Project Consortium +; Corresponding Author; McVean, Gil A. 1,2,*; Steering committee; Altshuler, David M. (Co-Chair) 3,4,5; Durbin, Richard M. (Co-Chair) 6; Abecasis, Goncalo R. 7; Bentley, David R. 8; Chakravarti, Aravinda 9; Clark, Andrew G. 10; Donnelly, Peter 1,2; Eichler, Evan E. 11; Flicek, Paul 12; Gabriel, Stacey B. 3; Gibbs, Richard A. 13; Green, Eric D. 14; Hurles, Matthew E. 6; Knoppers, Bartha M. 15; Korbel, Jan O. 16; Lander, Eric S. 3; Lee, Charles 17; Lehrach, Hans 18,19; Mardis, Elaine R. 20; Marth, Gabor T. (Principal Investigator) (Co-Chair) 21; Nickerson, Deborah A. 22; Schmidt, Jeanette P. 23; Sherry, Stephen T. 24; Wang, Jun 25,26,27; Wilson, Richard K. 20; Production group: Baylor College of Medicine; Dinh, Huyen 13; Kovar, Christie 13; Lee, Sandra 13; Lewis, Lora 13; Muzny, Donna 13; Reid, Jeff 13; Wang, Min 13; Production group: BGI-Shenzhen; Wang, Jun (Principal Investigator) 25,26,27; Fang, Xiaodong 25; Guo, Xiaosen 25; Jian, Min 25; Jiang, Hui 25; Jin, Xin 25; Li, Guoqing 25; Li, Jingxiang 25; Li, Yingrui 25; Li, Zhuo 25; Liu, Xiao 25; Lu, Yao 25; Ma, Xuedi 25; Su, Zhe 25; Tai, Shuaishuai 25; Tang, Meifang 25; Wang, Bo 25; Wang, Guangbiao 25; Wu, Honglong 25; Wu, Renhua 25; Yin, Ye 25; Zhang, Wenwei 25; Zhao, Jiao 25; Zhao, Meiru 25; Zheng, Xiaole 25; Zhou, Yan 25; Production group: Broad Institute of MIT and Harvard; Lander, Eric S. (Principal Investigator) 3; Gabriel, Stacey B. (Co-Chair) 3; Gupta, Namrata 3; Production group: European Bioinformatics Institute; Flicek, Paul (Principal Investigator); Clarke, Laura 12; Leinonen, Rasko 12; Smith, Richard E. 12; Zheng-Bradley, Xiangqun 12; Production group: Illumina; Bentley, David R. (Principal Investigator) 8; Grocock, Russell 8; Humphray, Sean 8; James, Terena 8; Kingsbury, Zoya 8; Production group: Max Planck Institute for Molecular Genetics; Lehrach, Hans (Principal Investigator) 18,19; Sudbrak, Ralf (Project Leader) 18; Albrecht, Marcus W. 28; Amstislavskiy, Vyacheslav S. 18; Borodina, Tatiana A. 28; Lienhard, Matthias 18; Mertes, Florian 18; Sultan, Marc 18; Timmermann, Bernd 18; Yaspo, Marie-Laure 18; Production group: US National Institutes of Health; Sherry, Stephen T. (Principal Investigator); Production group: University of Oxford; McVean, Gil A. (Principal Investigator) 2; Production group: Washington University in St Louis; Mardis, Elaine R. (Co-Principal Investigator) (Co-Chair); Wilson, Richard K. (Co-Principal Investigator) 20; Fulton, Lucinda 20; Fulton, Robert 20; Weinstock, George M. 20; Production group: Wellcome Trust Sanger Institute; Durbin, Richard M. (Principal Investigator) 6; Balasubramaniam, Senduran 6; Burton, John 6; Danecek, Petr 6; Keane, Thomas M. 6; Kolb-Kokocinski, Anja 6; McCarthy, Shane 6; Stalker, James 6; Quail, Michael 6; Analysis group: Affymetrix; Schmidt, Jeanette P. (Principal Investigator) 23; Davies, Christopher J. 23; Gollub, Jeremy 23; Webster, Teresa 23; Wong, Brant 23; Zhan, Yiping 23; Analysis group: Albert Einstein College of Medicine; Auton, Adam (Principal Investigator) 29; Analysis group: Baylor College of Medicine; Yu, Fuli (Project Leader) 13; Bainbridge, Matthew 13; Challis, Danny 13; Evani, Uday S. 13; Lu, James 13; Nagaswamy, Uma 13; Sabo, Aniko 13; Wang, Yi 13; Yu, Jin 13; Analysis group: BGI-Shenzhen; Coin, Lachlan J. M. 25; Fang, Lin 25; Li, Qibin 25; Li, Zhenyu 25; Lin, Haoxiang 25; Liu, Binghang 25; Luo, Ruibang 25; Qin, Nan 25; Shao, Haojing 25; Wang, Bingqiang 25; Xie, Yinlong 25; Ye, Chen 25; Yu, Chang 25; Zhang, Fan 25; Zheng, Hancheng 25; Zhu, Hongmei 25; Analysis group: Boston College; Garrison, Erik P. 21; Kural, Deniz 21; Lee, Wan-Ping 21; Fung Leong, Wen 21; Ward, Alistair N. 21; Wu, Jiantao 21; Zhang, Mengyao 21; Analysis group: Brigham and Women's Hospital; Lee, Charles (Principal Investigator); Griffin, Lauren 17; Hsieh, Chih-Heng 17; Mills, Ryan E. 17,30; Shi, Xinghua 17; von Grotthuss, Marcin 17; Zhang, Chengsheng 17; Analysis group: Broad Institute of MIT and Harvard; Daly, Mark J. (Principal Investigator) 3; DePristo, Mark A. (Project Leader) 3; Banks, Eric 3; Bhatia, Gaurav 3; Carneiro, Mauricio O. 3; del Angel, Guillermo 3; Genovese, Giulio 3; Handsaker, Robert E. 3,5; Hartl, Chris 3; McCarroll, Steven A. 3; Nemesh, James C. 3; Poplin, Ryan E. 3; Schaffner, Stephen F. 3; Shakir, Khalid 3; Analysis group: Cold Spring Harbor Laboratory; Yoon, Seungtai C. (Principal Investigator) 31; Lihm, Jayon 31; Makarov, Vladimir 32; Analysis group: Dankook University; Jin, Hanjun (Principal Investigator) 33; Kim, Wook 34; Cheol Kim, Ki 34; Analysis group: European Molecular Biology Laboratory; Korbel, Jan O. (Principal Investigator); Rausch, Tobias 16; Analysis group: European Bioinformatics Institute; Beal, Kathryn 12; Cunningham, Fiona 12; Herrero, Javier 12; McLaren, William M. 12; Ritchie, Graham R. S. 12; Analysis group: Cornell University; Clark, Andrew G. (Principal Investigator) 10; Gottipati, Srikanth 35; Keinan, Alon 10; Rodriguez-Flores, Juan L. 10; Analysis group: Harvard University; Sabeti, Pardis C. (Principal Investigator) 3,36; Grossman, Sharon R. 3,36; Tabrizi, Shervin 3,36; Tariyal, Ridhi 3,36; Analysis group: Human Gene Mutation Database; Cooper, David N. (Principal Investigator) 37; Ball, Edward V. 37; Stenson, Peter D. 37; Analysis group: Illumina; Barnes, Bret 38; Bauer, Markus 8; Keira Cheetham, R. 8; Cox, Tony 8; Eberle, Michael 8; Kahn, Scott 38; Murray, Lisa 8; Peden, John; Shaw, Richard 8; Analysis group: Leiden University Medical Center; Ye, Kai (Principal Investigator) 39; Analysis group: Louisiana State University; Batzer, Mark A. (Principal Investigator) 40; Konkel, Miriam K. 40; Walker, Jerilyn A. 40; Analysis group: Massachusetts General Hospital; MacArthur, Daniel G. (Principal Investigator) 41; Lek, Monkol 41; Analysis group: Max Planck Institute for Molecular Genetics; Sudbrak, (Project Leader) 18; Herwig, Ralf 18; Analysis group: Pennsylvania State University; Shriver, Mark D. (Principal Investigator) 42; Analysis group: Stanford University; Bustamante, Carlos D. (Principal Investigator) 43; Byrnes, Jake K. 44; De La Vega, Francisco M. 10; Gravel, Simon 43; Kenny, Eimear E. 43; Kidd, Jeffrey M. 43; Lacroute, Phil 43; Maples, Brian K. 43; Moreno-Estrada, Andres 43; Zakharia, Fouad 43; Analysis group: Tel-Aviv University; Halperin, Eran (Principal Investigator) 45,46,47; Baran, Yael 45; Analysis group: Translational Genomics Research Institute; Craig, David W. (Principal Investigator) 48; Christoforides, Alexis 48; Homer, Nils 49; Izatt, Tyler 48; Kurdoglu, Ahmet A. 48; Sinari, Shripad A. 48; Squire, Kevin 50; Analysis group: US National Institutes of Health; Xiao, Chunlin 24; Analysis group: University of California, San Diego; Sebat, Jonathan (Principal Investigator) 51,52; Bafna, Vineet 53; Ye, Kenny 54; Analysis group: University of California, San Francisco; Burchard, Esteban G. (Principal Investigator) 55; Hernandez, Ryan D. (Principal Investigator) 55; Gignoux, Christopher R. 55; Analysis group: University of California, Santa Cruz; Haussler, David (Principal Investigator) 56,57; Katzman, Sol J. 56; James Kent, W. 56; Analysis group: University of Chicago; Howie, Bryan 58; Analysis group: University College London; Ruiz-Linares, Andres (Principal Investigator) 59; Analysis group: University of Geneva; Dermitzakis, Emmanouil T. (Principal Investigator) 60,61,62; Lappalainen, Tuuli 60,61,62; Analysis group: University of Maryland School of Medicine; Devine, Scott E. (Principal Investigator) 63; Liu, Xinyue 63; Maroo, Ankit 63; Tallon, Luke J. 63; Analysis group: University of Medicine and Dentistry of New Jersey; Rosenfeld, Jeffrey A. (Principal Investigator) 64,65; Analysis group: University of Michigan; Min Kang, Hyun (Project Leader) 7; Anderson, Paul 7; Angius, Andrea 66; Bigham, Abigail 67; Blackwell, Tom 7; Busonero, Fabio 7,66,68; Cucca, Francesco 66,68; Fuchsberger, Christian 7; Jones, Chris 69; Jun, Goo 7; Li, Yun 70; Lyons, Robert 71; Maschio, Andrea 7,66,68; Porcu, Eleonora 7,66,68; Reinier, Fred 69; Sanna, Serena 66; Schlessinger, David 72; Sidore, Carlo 7,66,68; Tan, Adrian 7; Kate Trost, Mary 7; Analysis group: University of Montreal; Awadalla, Philip (Principal Investigator) 73; Hodgkinson, Alan 73; Analysis group: University of Oxford; Lunter, Gerton (Principal Investigator) 1; McVean, Gil A. (Principal Investigator) (Co-Chair) 2; Marchini, Jonathan L. (Principal Investigator) 1,2; Myers, Simon (Principal Investigator) 1,2; Churchhouse, Claire 2; Delaneau, Olivier 2; Gupta-Hinch, Anjali 1; Iqbal, Zamin 1; Mathieson, Iain 1; Rimmer, Andy 1; Xifara, Dionysia K. 1,2; Analysis group: University of Puerto Rico; Oleksyk, Taras K. (Principal Investigator) 74; Analysis group: University of Texas Health Sciences Center at Houston; Fu, Yunxin (Principal Investigator) 75; Liu, Xiaoming 75; Xiong, Momiao 75; Analysis group: University of Utah; Jorde, Lynn (Principal Investigator) 76; Witherspoon, David 76; Xing, Jinchuan 77; Analysis group: University of Washington; Eichler, Evan E. (Principal Investigator); Browning, Brian L. (Principal Investigator) 78; Alkan, Can 22,79; Hajirasouliha, Iman 80; Hormozdiari, Fereydoun 22; Ko, Arthur 22; Sudmant, Peter H. 22; Analysis group: Washington University in St Louis; Mardis, Elaine R. (Co-Principal Investigator); Chen, Ken 81; Chinwalla, Asif 20; Ding, Li 20; Dooling, David 20; Koboldt, Daniel C. 20; McLellan, Michael D. 20; Wallis, John W. 20; Wendl, Michael C. 20; Zhang, Qunyuan 20; Analysis group: Wellcome Trust Sanger Institute; Hurles, Matthew E. (Principal Investigator); Tyler-Smith, Chris (Principal Investigator); Albers, Cornelis A. 82; Ayub, Qasim 6; Chen, Yuan 6; Coffey, Alison J. 6; Colonna, Vincenza 6,83; Huang, Ni 6; Jostins, Luke 6; Li, Heng 3,6; Scally, Aylwyn 6; Walter, Klaudia 6; Xue, Yali 6; Zhang, Yujun 6; Analysis group: Yale University; Gerstein, Mark B. (Principal Investigator) 84,85,86; Abyzov, Alexej 84,86; Balasubramanian, Suganthi 86; Chen, Jieming 84; Clarke, Declan 87; Fu, Yao 84; Habegger, Lukas 84; Harmanci, Arif O. 84; Jin, Mike 86; Khurana, Ekta 86; Jasmine Mu, Xinmeng 84; Sisu, Cristina 84; Structural variation group: BGI-Shenzhen; Structural variation group: Brigham and Women's Hospital; Lee, Charles (Principal Investigator) (Co-Chair); Structural variation group: Boston College; Structural variation group: Broad Institute of MIT and Harvard; McCarroll, Steven A. (Project Leader) 3; Structural variation group: Cold Spring Harbor Laboratory; Structural variation group: Cornell University; Degenhardt, Jeremiah 10; Structural variation group: European Bioinformatics Institute; Structural variation group: European Molecular Biology Laboratory; Korbel, Jan O. (Principal Investigator) (Co-Chair); Stutz, Adrian M. 16; Structural variation group: Illumina; Structural variation group: Leiden University Medical Center; Structural variation group: Louisiana State University; Structural variation group: Stanford University; Structural variation group: Translational Genomics Research Institute; Structural variation group: US National Institutes of Health; Church, Deanna 24; Structural variation group: University of California, San Diego; Michaelson, Jacob J. 88; Structural variation group: University of Maryland School of Medicine; Structural variation group: University of Oxford; Structural variation group: University of Utah; Structural variation group: University of Washington; Eichler, Evan E. (Principal Investigator) (Co-Chair); Structural variation group: Washington University in St Louis; Structural variation group: Wellcome Trust Sanger Institute; Hurles, Matthew E. (Principal Investigator) (Co-Chair) 6; Blackburne, Ben 6; Lindsay, Sarah J. 6; Ning, Zemin 6; Structural variation group: Yale University; Exome group: Baylor College of Medicine; Exome group: BGI-Shenzhen; Exome group: Boston College; Exome group: Broad Institute of MIT and Harvard; DePristo, Mark A. 3; Exome group: Cornell University; Exome group: European Bioinformatics Institute; Exome group: Massachusetts General Hospital; Exome group: Stanford University; Exome group: Translational Genomics Research Institute; Exome group: US National Institutes of Health; Exome group: University of Geneva; Exome group: University of Michigan; Min Kang, Hyun 7; Exome group: University of Oxford; Exome group: Washington University in St Louis; Mardis, Elaine R. (Principal Investigator); Exome group: Wellcome Trust Sanger Institute; Exome group: Yale University; Functional interpretation group: Boston College; Functional interpretation group: Baylor College of Medicine; Yu, Fuli 13; Functional interpretation group: Broad Institute of MIT and Harvard; Functional interpretation group: Cold Spring Harbor Laboratory; Functional interpretation group: Cornell University; Functional interpretation group: Dankook University; Functional interpretation group: European Bioinformatics Institute; Functional interpretation group: Harvard University; Functional interpretation group: Massachusetts General Hospital; Functional interpretation group: Stanford University; Functional interpretation group: Translational Genomics Research Institute; Functional interpretation group: University of Geneva; Functional interpretation group: University of Medicine and Dentistry of New Jersey; Michelson, Leslie P. 64,65; Functional interpretation group: University of Montreal; Functional interpretation group: University of Oxford; Functional interpretation group: Washington University in St Louis; Functional interpretation group: Wellcome Trust Sanger Institute; Tyler-Smith, Chris (Principal Investigator) (Co-Chair); Frankish, Adam 6; Harrow, Jennifer 6; Functional interpretation group: Yale University; Data coordination centre group: Baylor College of Medicine; Fowler, Gerald 13; Hale, Walker 13; Kalra, Divya 13; Data coordination centre group: BGI-Shenzhen; Data coordination centre group: Broad Institute of MIT and Harvard; Data coordination centre group: European Bioinformatics Institute; Flicek, Paul (Principal Investigator) (Co-Chair); Clarke, Laura (Project Leader) 12; Barker, Jonathan 12; Kelman, Gavin 12; Kulesha, Eugene 12; Radhakrishnan, Rajesh 12; Roa, Asier 12; Smirnov, Dmitriy 12; Streeter, Ian 12; Toneva, Iliana 12; Vaughan, Brendan 12; Data coordination centre group: Illumina; Data coordination centre group: Max Planck Institute for Molecular Genetics; Data coordination centre group: Translational Genomics Research Institute; Data coordination centre group: US National Institutes of Health; Sherry, Stephen T. (Principal Investigator) (Co-Chair); Ananiev, Victor 24; Belaia, Zinaida 24; Beloslyudtsev, Dimitriy 24; Bouk, Nathan 24; Chen, Chao 24; Cohen, Robert 24; Cook, Charles 24; Garner, John 24; Hefferon, Timothy 24; Kimelman, Mikhail 24; Liu, Chunlei 24; Lopez, John 24; Meric, Peter 24; O'Sullivan, Chris 89; Ostapchuk, Yuri 24; Phan, Lon 24; Ponomarov, Sergiy 24; Schneider, Valerie 24; Shekhtman, Eugene 24; Sirotkin, Karl 24; Slotta, Douglas 24; Zhang, Hua 24; Data coordination centre group: University of California, Santa Cruz; Data coordination centre group: University of Michigan; Data coordination centre group: University of Oxford; Data coordination centre group: University of Washington; Data coordination centre group: Washington University in St Louis; Data coordination centre group: Wellcome Trust Sanger Institute; Data coordination centre group: Samples and ELSI group; Chakravarti, Aravinda (Co-Chair) 9; Knoppers, Bartha M. (Co-Chair) 15; Barnes, Kathleen C. 90; Beiswanger, Christine 91; Burchard, Esteban G. 55; Bustamante, Carlos D. 43; Cai, Hongyu 25; Cao, Hongzhi 25; Durbin, Richard M. 6; Gharani, Neda 91; Henn, Brenna 43; Jones, Danielle 35; Jorde, Lynn 76; Kaye, Jane S. 92; Kent, Alastair 93; Kerasidou, Angeliki 1; Mathias, Rasika 94; Ossorio, Pilar N. 95,96; Parker, Michael 97; Reich, David 5; Rotimi, Charles N. 98; Royal, Charmaine D. 99; Sandoval, Karla 43; Su, Yeyang 25; Sudbrak, Ralf 18; Tian, Zhongming 25; Tishkoff, Sarah 100; Toji, Lorraine H. 91; Tyler-Smith, Chris 6; Via, Marc 101; Wang, Yuhong 25; Yang, Huanming 25; Yang, Ling 25; Zhu, Jiayong 25; Sample collection: British from England and Scotland (GBR); Bodmer, Walter 102; Sample collection: Colombians in Medellin, Colombia (CLM); Bedoya, Gabriel 103; Ruiz-Linares, Andres 59; Sample collection: Han Chinese South (CHS); Zhi Ming, Cai 25; Yang, Gao 104; Jia You, Chu 105; Sample collection: Finnish in Finland (FIN); Peltonen, Leena 112; Sample collection: Iberian populations in Spain (IBS); Garcia-Montero, Andres 106; Orfao, Alberto 107; Sample collection: Puerto Ricans in Puerto Rico (PUR); Dutil, Julie 108; Martinez-Cruzado, Juan C. 74; Oleksyk, Taras K. 74; Sample collection: Scientific management; Brooks, Lisa D. 109; Felsenfeld, Adam L. 109; McEwen, Jean E. 109; Clemm, Nicholas C. 109; Duncanson, Audrey 110; Dunn, Michael 110; Guyer, Mark S. 109; Peterson, Jane L. 109; Sample collection: Writing group; Abecasis, Goncalo R.; Auton, Adam 29
[Article]
Nature.
491(7422):56-65, November 1, 2012.
(Format: HTML, PDF)
: By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.
(C) 2012 Nature Publishing Group