A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium; The 1000 Genomes Consortium (Participants are arranged by project role, then by institution alphabetically, and finally alphabetically within institutions except for Principal Investigators and Project Leaders, as indicated.) 79; Corresponding author; Durbin, Richard M. 1; Steering committee; Altshuler, David L. (Co-Chair) 2,3,4; Durbin, Richard M. (Co-Chair) 1; Abecasis, Goncalo R. 5; Bentley, David R. 6; Chakravarti, Aravinda 7; Clark, Andrew G. 8; Collins, Francis S. 9; De La Vega, Francisco M. 10; Donnelly, Peter 11; Egholm, Michael 12; Flicek, Paul 13; Gabriel, Stacey B. 2; Gibbs, Richard A. 14; Knoppers, Bartha M. 15; Lander, Eric S. 2; Lehrach, Hans 16; Mardis, Elaine R. 17; McVean, Gil A. 11,18; Nickerson, Debbie A. 19; Peltonen, Leena 80; Schafer, Alan J. 20; Sherry, Stephen T. 21; Wang, Jun 22,23; Wilson, Richard K. 17; Production group: Baylor College of Medicine; Gibbs, Richard A. (Principal Investigator) 14; Deiros, David 14; Metzker, Mike 14; Muzny, Donna 14; Reid, Jeff 14; Wheeler, David 14; BGI-Shenzhen; Wang, Jun (Principal Investigator) 22,23; Li, Jingxiang 22; Jian, Min 22; Li, Guoqing 22; Li, Ruiqiang 22,23; Liang, Huiqing 22; Tian, Geng 22; Wang, Bo 22; Wang, Jian 22; Wang, Wei 22; Yang, Huanming 22; Zhang, Xiuqing 22; Zheng, Huisong 22; Broad Institute of MIT and Harvard; Lander, Eric S. (Principal Investigator) 2; Altshuler, David L. 2,3,4; Ambrogio, Lauren 2; Bloom, Toby 2; Cibulskis, Kristian 2; Fennell, Tim J. 2; Gabriel, Stacey B. (Co-Chair) 2; Jaffe, David B. 2; Shefler, Erica 2; Sougnez, Carrie L. 2; Illumina; Bentley, David R. (Principal Investigator) 6; Gormley, Niall 6; Humphray, Sean 6; Kingsbury, Zoya 6; Koko-Gonzales, Paula 6; Stone, Jennifer 6; Life Technologies; McKernan, Kevin J. (Principal Investigator) 24; Costa, Gina L. 24; Ichikawa, Jeffry K. 24; Lee, Clarence C. 24; Max Planck Institute for Molecular Genetics; Sudbrak, Ralf (Project Leader) 16; Lehrach, Hans (Principal Investigator) 16; Borodina, Tatiana A. 16; Dahl, Andreas 25; Davydov, Alexey N. 16; Marquardt, Peter 16; Mertes, Florian 16; Nietfeld, Wilfiried 16; Rosenstiel, Philip 26; Schreiber, Stefan 26; Soldatov, Aleksey V. 16; Timmermann, Bernd 16; Tolzmann, Marius 16; Roche Applied Science; Egholm, Michael (Principal Investigator) 12; Affourtit, Jason 27; Ashworth, Dana 27; Attiya, Said 27; Bachorski, Melissa 27; Buglione, Eli 27; Burke, Adam 27; Caprio, Amanda 27; Celone, Christopher 27; Clark, Shauna 27; Conners, David 27; Desany, Brian 27; Gu, Lisa 27; Guccione, Lorri 27; Kao, Kalvin 27; Kebbel, Andrew 27; Knowlton, Jennifer 27; Labrecque, Matthew 27; McDade, Louise 27; Mealmaker, Craig 27; Minderman, Melissa 27; Nawrocki, Anne 27; Niazi, Faheem 27; Pareja, Kristen 27; Ramenani, Ravi 27; Riches, David 27; Song, Wanmin 27; Turcotte, Cynthia 27; Wang, Shally 27; Washington University in St Louis; Mardis, Elaine R. (Co-Chair) (Co-Principal Investigator) 17; Wilson, Richard K. (Co-Principal Investigator) 17; Dooling, David 17; Fulton, Lucinda 17; Fulton, Robert 17; Weinstock, George 17; Wellcome Trust Sanger Institute; Durbin, Richard M. (Principal Investigator) 1; Burton, John 1; Carter, David M. 1; Churcher, Carol 1; Coffey, Alison 1; Cox, Anthony 1; Palotie, Aarno 1,28; Quail, Michael 1; Skelly, Tom 1; Stalker, James 1; Swerdlow, Harold P. 1; Turner, Daniel 1; Analysis group: Agilent Technologies; De Witte, Anniek 29; Giles, Shane 29; Baylor College of Medicine; Bainbridge, Matthew 14; Challis, Danny 14; Sabo, Aniko 14; Yu, Fuli 14; Yu, Jin 14; Fang, Xiaodong 22; Guo, Xiaosen 22; Li, Yingrui 22; Luo, Ruibang 22; Tai, Shuaishuai 22; Wu, Honglong 22; Zheng, Hancheng 22; Zheng, Xiaole 22; Zhou, Yan 22; Boston College; Marth, Gabor T. (Principal Investigator) 30; Garrison, Erik P. 30; Huang, Weichun 31; Indap, Amit 30; Kural, Deniz 30; Lee, Wan-Ping 30; Fung Leong, Wen 30; Quinlan, Aaron R. 32; Stewart, Chip 30; Stromberg, Michael P. 33; Ward, Alistair N. 30; Wu, Jiantao 30; Brigham and Women's Hospital; Lee, Charles (Principal Investigator) 34; Mills, Ryan E. 34; Shi, Xinghua 34; Daly, Mark J. (Principal Investigator) 2; DePristo, Mark A. (Project Leader) 2; Ball, Aaron D. 2; Banks, Eric 2; Browning, Brian L. 35; Garimella, Kiran V. 2; Grossman, Sharon R. 2,36; Handsaker, Robert E. 2; Hanna, Matt 2; Hartl, Chris 2; Kernytsky, Andrew M. 2; Korn, Joshua M. 2; Li, Heng 2; Maguire, Jared R. 2; McCarroll, Steven A. 2,4; McKenna, Aaron 2; Nemesh, James C. 2; Philippakis, Anthony A. 2; Poplin, Ryan E. 2; Price, Alkes 37; Rivas, Manuel A. 2; Sabeti, Pardis C. 2,36; Schaffner, Stephen F. 2; Shlyakhter, Ilya A. 2,36; Cardiff University, The Human Gene Mutation Database; Cooper, David N. (Principal Investigator) 38; Ball, Edward V. 38; Mort, Matthew 38; Phillips, Andrew D. 38; Stenson, Peter D. 38; Cold Spring Harbor Laboratory; Sebat, Jonathan (Principal Investigator) 39; Makarov, Vladimir 40; Ye, Kenny 41; Yoon, Seungtai C. 42; Cornell and Stanford Universities; Bustamante, Carlos D. (Co-Principal Investigator) 43; Clark, Andrew G. (Co-Principal Investigator) 8; Boyko, Adam 43; Degenhardt, Jeremiah 8; Gravel, Simon 43; Gutenkunst, Ryan N. 44; Kaganovich, Mark 43; Keinan, Alon 8; Lacroute, Phil 43; Ma, Xin 8; Reynolds, Andy 8; European Bioinformatics Institute; Clarke, Laura (Project Leader) 13; Flicek, Paul (Co-Chair, DCC) (Principal Investigator Principal Investigator) 13; Cunningham, Fiona 13; Herrero, Javier 13; Keenen, Stephen 13; Kulesha, Eugene 13; Leinonen, Rasko 13; McLaren, William M. 13; Radhakrishnan, Rajesh 13; Smith, Richard E. 13; Zalunin, Vadim 13; Zheng-Bradley, Xiangqun 13; European Molecular Biology Laboratory; Korbel, Jan O. (Principal Investigator) 45; Stutz, Adrian M. 45; Humphray, Sean (Project Leader) 6; Bauer, Markus 6; Cheetham, Keira R. 6; Cox, Tony 6; Eberle, Michael 6; James, Terena 6; Kahn, Scott 6; Murray, Lisa 6; Johns Hopkins University; Leiden University Medical Center; Ye, Kai 46; De La Vega, Francisco M. (Principal Investigator) 10; Fu, Yutao 24; Hyland, Fiona C. L. 10; Manning, Jonathan M. 24; McLaughlin, Stephen F. 24; Peckham, Heather E. 24; Sakarya, Onur 10; Sun, Yongming A. 10; Tsung, Eric F. 24; Louisiana State University; Batzer, Mark A. (Principal Investigator) 47; Konkel, Miriam K. 47; Walker, Jerilyn A. 47; Albrecht, Marcus W. 16; Amstislavskiy, Vyacheslav S. 16; Herwig, Ralf 16; Parkhomchuk, Dimitri V. 16; US National Institutes of Health; Sherry, Stephen T. (Co-Chair, DCC) (Principal Investigator) 21; Agarwala, Richa 21; Khouri, Hoda M. 21; Morgulis, Aleksandr O. 21; Paschall, Justin E. 21; Phan, Lon D. 21; Rotmistrovsky, Kirill E. 21; Sanders, Robert D. 21; Shumway, Martin F. 21; Xiao, Chunlin 21; Oxford University; McVean, Gil A. (Co-Chair, Population Genetics) (Principal Investigator) 11,18; Auton, Adam 11; Iqbal, Zamin 11; Lunter, Gerton 11; Marchini, Jonathan L. 11,18; Moutsianas, Loukas 18; Myers, Simon 11,18; Tumian, Afidalina 18; Desany, Brian (Project Leader) 27; Knight, James 27; Winer, Roger 27; The Translational Genomics Research Institute; Craig, David W. (Principal Investigator) 48; Beckstrom-Sternberg, Steve M. 48; Christoforides, Alexis 48; Kurdoglu, Ahmet A. 48; Pearson, John V. 48; Sinari, Shripad A. 48; Tembe, Waibhav D. 48; University of California, Santa Cruz; Haussler, David (Principal Investigator) 49; Hinrichs, Angie S. 49; Katzman, Sol J. 49; Kern, Andrew 49; Kuhn, Robert M. 49; University of Chicago; Przeworski, Molly (Co-Chair, Population Genetics) (Principal Investigator) 50; Hernandez, Ryan D. 51; Howie, Bryan 52; Kelley, Joanna L. 52; Cord Melton, S. 52; University of Michigan; Abecasis, Goncalo R. (Co-Chair Principal Investigator) 5; Li, Yun (Project Leader) 5; Anderson, Paul 5; Blackwell, Tom 5; Chen, Wei 5; Cookson, William O. 53; Ding, Jun 5; Min Kang, Hyun 5; Lathrop, Mark 54; Liang, Liming 55; Moffatt, Miriam F. 53; Scheet, Paul 56; Sidore, Carlo 5; Snyder, Matthew 5; Zhan, Xiaowei 5; Zollner, Sebastian 5; University of Montreal; Awadalla, Philip (Principal Investigator) 57; Casals, Ferran 58; Idaghdour, Youssef 58; Keebler, John 58; Stone, Eric A. 58; Zilversmit, Martine 58; University of Utah; Jorde, Lynn (Principal Investigator) 59; Xing, Jinchuan 59; University of Washington; Eichler, Evan E. (Principal Investigator) 60; Aksay, Gozde 19; Alkan, Can 60; Hajirasouliha, Iman 61; Hormozdiari, Fereydoun 61; Sahinalp, Cenk S. 61; Sudmant, Peter H. 19; Mardis, Elaine R. (Co-Principal Investigator) 17; Chen, Ken 17; Chinwalla, Asif 17; Ding, Li 17; Koboldt, Daniel C. 17; McLellan, Mike D. 17; Wallis, John W. 17; Wendl, Michael C. 17; Zhang, Qunyuan 17; Albers, Cornelis A. 62; Ayub, Qasim 1; Balasubramaniam, Senduran 1; Barrett, Jeffrey C. 1; Chen, Yuan 1; Conrad, Donald F. 1; Danecek, Petr 1; Dermitzakis, Emmanouil T. 63; Hu, Min 1; Huang, Ni 1; Hurles, Matt E. 1; Jin, Hanjun 64; Jostins, Luke 1; Keane, Thomas M. 1; Quang Le, Si 1; Lindsay, Sarah 1; Long, Quan 1; MacArthur, Daniel G. 1; Montgomery, Stephen B. 63; Parts, Leopold 1; Tyler-Smith, Chris 1; Walter, Klaudia 1; Zhang, Yujun 1; Yale and Stanford Universities; Gerstein, Mark B. (Co-Principal Investigator) 65,66; Snyder, Michael (Co-Principal Investigator) 43; Abyzov, Alexej 65; Balasubramanian, Suganthi 67; Bjornson, Robert 66; Du, Jiang 66; Grubert, Fabian 43; Habegger, Lukas 65; Haraksingh, Rajini 65; Jee, Justin 65; Khurana, Ekta 67; Lam, Hugo Y. K. 43; Leng, Jing 65; Jasmine Mu, Xinmeng 65; Urban, Alexander E. 43,68; Zhang, Zhengdong 67; Structural variation group: BGI-Shenzhen; Lee, Charles (Co-Chair Principal Investigator) 34; McCarroll, Steven A. (Project Leader) 2,4; DePristo, Mark A. 2; Korbel, Jan O. 45; De La Vega, Francisco M. (Principal Invesigator) 10; Blackwell, Tom (Project Leader) 5; Eichler, Evan E. (Co-Chair) (Principal Investigator) 60; Kidd, Jeffrey M. 19,43; Hurles, Matt E. (Co-Chair) (Principal Investigator) 1; Exon pilot group: Baylor College of Medicine; Gibbs, Richard A. (Co-Chair) (Principal Investigator) 14; Coafra, Cristian 14; Dinh, Huyen 14; Kovar, Christie 14; Lee, Sandy 14; Nazareth, Lynne 14; Marth, Gabor T. (Co-Chair) (Principal Investigator) 30; Wilkinson, Jane 2; Flicek, Paul (Principal Investigator) 13; Sherry, Stephen T. (Principal Investigator) 21; Abecasis, Goncalo R. (Principal Investigator) 5; Mardis, Elaine R. (Principal Investigator) 17; Coffey, Allison 1; Scott, Carol 1; Yale University; Gerstein, Mark B. (Principal Investigator) 65,66; Samples and ELSI group; Chakravarti, Aravinda (Co-Chair) 7; Knoppers, Bartha M. (Co-Chair) 15; Bustamante, Carlos D. 43; Gharani, Neda 69; Jorde, Lynn 59; Kaye, Jane S. 70; Kent, Alastair 71; Li, Taosha 22; McGuire, Amy L. 72; Ossorio, Pilar N. 73; Rotimi, Charles N. 74; Su, Yeyang 22; Toji, Lorraine H. 69; Scientific management; Brooks, Lisa D. 75; Felsenfeld, Adam L. 75; McEwen, Jean E. 75; Abdallah, Assya 76; Juenger, Christopher R. 77; Clemm, Nicholas C. 75; Duncanson, Audrey 20; Green, Eric D. 78; Guyer, Mark S. 75; Peterson, Jane L. 75; Writing group
[Article]
Nature.
467(7319):1061-1073, October 28, 2010.
(Format: HTML, PDF)
: The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10-8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.
(C) 2010 Nature Publishing Group