A map of human genome variation from population-scale sequencing

David L. Altshuler, Richard M. Durbin, Gonçalo R. Abecasis, David R. Bentley, Aravinda Chakravarti, Andrew G. Clark, Francis S. Collins, Francisco M. De La Vega, Peter Donnelly, Michael Egholm, Paul Flicek, Stacey B. Gabriel, Richard A. Gibbs, Bartha M. Knoppers, Eric S. Lander, Hans Lehrach, Elaine R. Mardis, Gil A. McVean, Debbie A. Nickerson, Leena PeltonenAlan J. Schafer, Stephen T. Sherry, Jun Wang, Richard K. Wilson, David Deiros, Mike Metzker, Donna Muzny, Jeff Reid, David Wheeler, Shenzhen Jun Wang, Jingxiang Li, Min Jian, Guoqing Li, Ruiqiang Li, Huiqing Liang, Geng Tian, Bo Wang, Jian Wang, Wei Wang, Huanming Yang, Xiuqing Zhang, Huisong Zheng, Lauren Ambrogio, Toby Bloom, Kristian Cibulskis, Tim J. Fennell, David B. Jaffe, Erica Shefler, Carrie L. Sougnez, Illumina David R Bentley, Niall Gormley, Sean Humphray, Zoya Kingsbury, Paula Koko-Gonzales, Jennifer Stone, Kevin J. Mc Kernan, Gina L. Costa, Jeffry K. Ichikawa, Clarence C. Lee, Ralf Sudbrak, Tatiana A. Borodina, Andreas Dahl, Alexey N. Davydov, Peter Marquardt, Florian Mertes, Wilfiried Nietfeld, Philip Rosenstiel, Stefan Schreiber, Aleksey V. Soldatov, Bernd Timmermann, Marius Tolzmann, Jason Affourtit, Dana Ashworth, Said Attiya, Melissa Bachorski, Eli Buglione, Adam Burke, Amanda Caprio, Christopher Celone, Shauna Clark, David Conners, Brian Desany, Lisa Gu, Lorri Guccione, Kalvin Kao, Andrew Kebbel, Jennifer Knowlton, Matthew Labrecque, Louise McDade, Craig Mealmaker, Melissa Minderman, Anne Nawrocki, Faheem Niazi, Kristen Pareja, Ravi Ramenani, David Riches, Wanmin Song, Cynthia Turcotte, Shally Wang, David Dooling, Lucinda Fulton, Robert Fulton, George Weinstock, John Burton, David M. Carter, Carol Churcher, Alison Coffey, Anthony Cox, Aarno Palotie, Michael Quail, Tom Skelly, James Stalker, Harold P. Swerdlow, Daniel Turner, Anniek De Witte, Shane Giles, Matthew Bainbridge, Danny Challis, Aniko Sabo, Fuli Yu, Jin Yu, Xiaodong Fang, Xiaosen Guo, Yingrui Li, Ruibang Luo, Shuaishuai Tai, Honglong Wu, Hancheng Zheng, Xiaole Zheng, Yan Zhou, Gabor T. Marth, Erik P. Garrison, Weichun Huang, Amit Indap, Deniz Kural, Wan Ping Lee, Wen Fung Leong, Aaron R. Quinlan, Chip Stewart, Michael P. Stromberg, Alistair N. Ward, Jiantao Wu, Charles Lee, Ryan E. Mills, Xinghua Shi, Mark J. Daly, Mark A. DePristo, Aaron D. Ball, Eric Banks, Brian L. Browning, Kiran V. Garimella, Sharon R. Grossman, Robert E. Handsaker, Matt Hanna, Chris Hartl, Andrew M. Kernytsky, Joshua M. Korn, Heng Li, Jared R. Maguire, Aaron McKenna, James C. Nemesh, Anthony A. Philippakis, Ryan E. Poplin, Alkes Price, Manuel A. Rivas, Pardis C. Sabeti, Stephen F. Schaffner, Ilya A. Shlyakhter, David N. Cooper, Edward V. Ball, Matthew Mort, Andrew D. Phillips, Peter D. Stenson, Jonathan Sebat, Vladimir Makarov, Kenny Ye, Seungtai C. Yoon, Carlos D. Bustamante, Adam Boyko, Jeremiah Degenhardt, Simon Gravel, Ryan N. Gutenkunst, Mark Kaganovich, Alon Keinan, Phil Lacroute, Xin Ma, Andy Reynolds, Laura Clarke, Fiona Cunningham, Javier Herrero, Stephen Keenen, Eugene Kulesha, Rasko Leinonen, William M. McLaren, Rajesh Radhakrishnan, Richard E. Smith, Vadim Zalunin, Jan O. Korbel, Adrian M. Stütz, Illumina Sean Humphray, Markus Bauer, R. Keira Cheetham, Tony Cox, Michael Eberle, Terena James, Scott Kahn, Lisa Murray, Kai Ye, Yutao Fu, Fiona C L Hyland, Jonathan M. Manning, F. McLaughlin Stephen, Heather E. Peckham, Onur Sakarya, Yongming A. Sun, Eric F. Tsung, A. Batzer Mark, Miriam K. Konkel, Jerilyn A. Walker, Marcus W. Albrecht, Vyacheslav S. Amstislavskiy, Ralf Herwig, Dimitri V. Parkhomchuk, Richa Agarwala, Hoda M. Khouri, Aleksandr O. Morgulis, Justin E. Paschall, Lon D. Phan, Kirill E. Rotmistrovsky, Robert D. Sanders, Martin F. Shumway, Chunlin Xiao, A. McVean Gil, Adam Auton, Zamin Iqbal, Gerton Lunter, Jonathan L. Marchini, Loukas Moutsianas, Simon Myers, Afidalina Tumian, James Knight, Roger Winer, David W. Craig, Stephen M Beckstrom-Sternberg, Alexis Christoforides, Ahmet A. Kurdoglu, John V. Pearson, Shripad A. Sinari, Waibhav D. Tembe, David Haussler, Angie S. Hinrichs, Sol J. Katzman, Andrew Kern, Robert M. Kuhn, Molly Przeworski, Ryan D. Hernandez, Bryan Howie, Joanna L. Kelley, S. Cord Melton, Yun Li, Paul Anderson, Tom Blackwell, Wei Chen, William O. Cookson, Jun Ding, Hyun Min Kang, Mark Lathrop, Liming Liang, Miriam F. Moffatt, Paul Scheet, Carlo Sidore, Matthew Snyder, Xiaowei Zhan, Sebastian Zöllner, Philip Awadalla, Ferran Casals, Youssef Idaghdour, John Keebler, Eric A. Stone, Martine Zilversmit, Lynn Jorde, Jinchuan Xing, Evan E. Eichler, Gozde Aksay, Can Alkan, Iman Hajirasouliha, Fereydoun Hormozdiari, Jeffrey M. Kidd, S. CenkSahinalp, Peter H. Sudmant, Ken Chen, Asif Chinwalla, Li Ding, Daniel C. Koboldt, Mike D. McLellan, John W. Wallis, Michael C. Wendl, Qunyuan Zhang, Cornelis A. Albers, Qasim Ayub, Senduran Balasubramaniam, Jeffrey C. Barrett, Yuan Chen, Donald F. Conrad, Petr Danecek, Emmanouil T. Dermitzakis, Min Hu, Ni Huang, E. Hurles Matt, Hanjun Jin, Luke Jostins, Thomas M. Keane, Si Quang Le, Sarah Lindsay, Quan Long, Daniel G. MacArthur, Stephen B. Montgomery, Leopold Parts, Tyler-Smith Chris Tyler-Smith, Klaudia Walter, Yujun Zhang, Mark B. Gerstein, Michael Snyder, Alexej Abyzov, Suganthi Balasubramanian, Robert Bjornson, Fabian Grubert, Lukas Habegger, Rajini Haraksingh, Ekta Khurana, Hugo Y K Lam, Jing Leng, Xinmeng Jasmine Mu, Alexander E. Urban, Zhengdong Zhang, Steven A. McCarroll, Xiangqun Zheng-Bradley, Mark A. Batzer, Matt E. Hurles, Jiang Du, Justin Jee, Cristian Coafra, Huyen Dinh, Christie Kovar, Sandy Lee, Lynne Nazareth, Jane Wilkinson, Allison Coffey, Carol Scott, Chris Tyler-Smith, Neda Gharani, Jane S. Kaye, Alastair Kent, Taosha Li, Amy L. McGuire, Pilar N. Ossorio, Charles N. Rotimi, Yeyang Su, Lorraine H. Toji, Adam L. Felsenfeld, Jean E. McEwen, Assya Abdallah, Christopher R. Juenger, Nicholas C. Clemm, Audrey Duncanson, Eric D. Green, Mark S. Guyer, Jane L. Peterson

5050 Scopus citations

Abstract

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 g-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.

Original languageEnglish (US)
Pages (from-to)1061-1073
Number of pages13
JournalNature
Volume467
Issue number7319
DOIs
StatePublished - Oct 28 2010
Externally publishedYes

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A map of human genome variation from population-scale sequencing. / Altshuler, David L.; Durbin, Richard M.; Abecasis, Gonçalo R.; Bentley, David R.; Chakravarti, Aravinda; Clark, Andrew G.; Collins, Francis S.; De La Vega, Francisco M.; Donnelly, Peter; Egholm, Michael; Flicek, Paul; Gabriel, Stacey B.; Gibbs, Richard A.; Knoppers, Bartha M.; Lander, Eric S.; Lehrach, Hans; Mardis, Elaine R.; McVean, Gil A.; Nickerson, Debbie A.; Peltonen, Leena; Schafer, Alan J.; Sherry, Stephen T.; Wang, Jun; Wilson, Richard K.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Wheeler, David; Wang, Shenzhen Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Ambrogio, Lauren; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Bentley, Illumina David R; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; Mc Kernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Sudbrak, Ralf; Borodina, Tatiana A.; Dahl, Andreas; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Rosenstiel, Philip; Schreiber, Stefan; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; Burton, John; Carter, David M.; Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Quail, Michael; Skelly, Tom; Stalker, James; Swerdlow, Harold P.; Turner, Daniel; De Witte, Anniek; Giles, Shane; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Fang, Xiaodong; Guo, Xiaosen; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Marth, Gabor T.; Garrison, Erik P.; Huang, Weichun; Indap, Amit; Kural, Deniz; Lee, Wan Ping; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Daly, Mark J.; DePristo, Mark A.; Ball, Aaron D.; Banks, Eric; Browning, Brian L.; Garimella, Kiran V.; Grossman, Sharon R.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Price, Alkes; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Shlyakhter, Ilya A.; Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Bustamante, Carlos D.; Boyko, Adam; Degenhardt, Jeremiah; Gravel, Simon; Gutenkunst, Ryan N.; Kaganovich, Mark; Keinan, Alon; Lacroute, Phil; Ma, Xin; Reynolds, Andy; Clarke, Laura; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, William M.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Korbel, Jan O.; Stütz, Adrian M.; Humphray, Illumina Sean; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott; Murray, Lisa; Ye, Kai; Fu, Yutao; Hyland, Fiona C L; Manning, Jonathan M.; Stephen, F. McLaughlin; Peckham, Heather E.; Sakarya, Onur; Sun, Yongming A.; Tsung, Eric F.; Mark, A. Batzer; Konkel, Miriam K.; Walker, Jerilyn A.; Albrecht, Marcus W.; Amstislavskiy, Vyacheslav S.; Herwig, Ralf; Parkhomchuk, Dimitri V.; Agarwala, Richa; Khouri, Hoda M.; Morgulis, Aleksandr O.; Paschall, Justin E.; Phan, Lon D.; Rotmistrovsky, Kirill E.; Sanders, Robert D.; Shumway, Martin F.; Xiao, Chunlin; Gil, A. McVean; Auton, Adam; Iqbal, Zamin; Lunter, Gerton; Marchini, Jonathan L.; Moutsianas, Loukas; Myers, Simon; Tumian, Afidalina; Knight, James; Winer, Roger; Craig, David W.; Beckstrom-Sternberg, Stephen M; Christoforides, Alexis; Kurdoglu, Ahmet A.; Pearson, John V.; Sinari, Shripad A.; Tembe, Waibhav D.; Haussler, David; Hinrichs, Angie S.; Katzman, Sol J.; Kern, Andrew; Kuhn, Robert M.; Przeworski, Molly; Hernandez, Ryan D.; Howie, Bryan; Kelley, Joanna L.; Melton, S. Cord; Li, Yun; Anderson, Paul; Blackwell, Tom; Chen, Wei; Cookson, William O.; Ding, Jun; Kang, Hyun Min; Lathrop, Mark; Liang, Liming; Moffatt, Miriam F.; Scheet, Paul; Sidore, Carlo; Snyder, Matthew; Zhan, Xiaowei; Zöllner, Sebastian; Awadalla, Philip; Casals, Ferran; Idaghdour, Youssef; Keebler, John; Stone, Eric A.; Zilversmit, Martine; Jorde, Lynn; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; CenkSahinalp, S.; Sudmant, Peter H.; Chen, Ken; Chinwalla, Asif; Ding, Li; Koboldt, Daniel C.; McLellan, Mike D.; Wallis, John W.; Wendl, Michael C.; Zhang, Qunyuan; Albers, Cornelis A.; Ayub, Qasim; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Chen, Yuan; Conrad, Donald F.; Danecek, Petr; Dermitzakis, Emmanouil T.; Hu, Min; Huang, Ni; Matt, E. Hurles; Jin, Hanjun; Jostins, Luke; Keane, Thomas M.; Quang Le, Si; Lindsay, Sarah; Long, Quan; MacArthur, Daniel G.; Montgomery, Stephen B.; Parts, Leopold; Chris Tyler-Smith, Tyler-Smith; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Balasubramanian, Suganthi; Bjornson, Robert; Grubert, Fabian; Habegger, Lukas; Haraksingh, Rajini; Khurana, Ekta; Lam, Hugo Y K; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; McCarroll, Steven A.; Zheng-Bradley, Xiangqun; Batzer, Mark A.; Hurles, Matt E.; Du, Jiang; Jee, Justin; Coafra, Cristian; Dinh, Huyen; Kovar, Christie; Lee, Sandy; Nazareth, Lynne; Wilkinson, Jane; Coffey, Allison; Scott, Carol; Tyler-Smith, Chris; Gharani, Neda; Kaye, Jane S.; Kent, Alastair; Li, Taosha; McGuire, Amy L.; Ossorio, Pilar N.; Rotimi, Charles N.; Su, Yeyang; Toji, Lorraine H.; Felsenfeld, Adam L.; McEwen, Jean E.; Abdallah, Assya; Juenger, Christopher R.; Clemm, Nicholas C.; Duncanson, Audrey; Green, Eric D.; Guyer, Mark S.; Peterson, Jane L.

In: Nature, Vol. 467, No. 7319, 28.10.2010, p. 1061-1073.

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