A map of human genome variation from population-scale sequencing View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-10-28

AUTHORS

Richard M. Durbin, 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 Peltonen, Alan J. Schafer, Stephen T. Sherry, Jun Wang, Richard K. Wilson, Richard A. Gibbs, David Deiros, Mike Metzker, Donna Muzny, Jeff Reid, David Wheeler, 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, Eric S. Lander, David L. Altshuler, Lauren Ambrogio, Toby Bloom, Kristian Cibulskis, Tim J. Fennell, Stacey B. Gabriel, David B. Jaffe, Erica Shefler, Carrie L. Sougnez, David R. Bentley, Niall Gormley, Sean Humphray, Zoya Kingsbury, Paula Koko-Gonzales, Jennifer Stone, Kevin J. McKernan, Gina L. Costa, Jeffry K. Ichikawa, Clarence C. Lee, Ralf Sudbrak, Hans Lehrach, 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, Michael Egholm, 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, Elaine R. Mardis, Richard K. Wilson, David Dooling, Lucinda Fulton, Robert Fulton, George Weinstock, Richard M. Durbin, 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, Richard A. Gibbs, David Wheeler, Matthew Bainbridge, Danny Challis, Aniko Sabo, Fuli Yu, Jin Yu, Jun Wang, Xiaodong Fang, Xiaosen Guo, Ruiqiang Li, Yingrui Li, Ruibang Luo, Shuaishuai Tai, Honglong Wu, Hancheng Zheng, Xiaole Zheng, Yan Zhou, Guoqing Li, Jian Wang, Huanming Yang, 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, David L. Altshuler, Aaron D. Ball, Eric Banks, Toby Bloom, Brian L. Browning, Kristian Cibulskis, Tim J. Fennell, Kiran V. Garimella, Sharon R. Grossman, Robert E. Handsaker, Matt Hanna, Chris Hartl, David B. Jaffe, Andrew M. Kernytsky, Joshua M. Korn, Heng Li, Jared R. Maguire, Steven A. McCarroll, Aaron McKenna, James C. Nemesh, Anthony A. Philippakis, Ryan E. Poplin, Alkes Price, Manuel A. Rivas, Pardis C. Sabeti, Stephen F. Schaffner, Erica Shefler, 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, Andrew G. Clark, Adam Boyko, Jeremiah Degenhardt, Simon Gravel, Ryan N. Gutenkunst, Mark Kaganovich, Alon Keinan, Phil Lacroute, Xin Ma, Andy Reynolds, Laura Clarke, Paul Flicek, Fiona Cunningham, Javier Herrero, Stephen Keenen, Eugene Kulesha, Rasko Leinonen, William M. McLaren, Rajesh Radhakrishnan, Richard E. Smith, Vadim Zalunin, Xiangqun Zheng-Bradley, Jan O. Korbel, Adrian M. Stütz, Sean Humphray, Markus Bauer, R. Keira Cheetham, Tony Cox, Michael Eberle, Terena James, Scott Kahn, Lisa Murray, Aravinda Chakravarti, Kai Ye, Francisco M. De La Vega, Yutao Fu, Fiona C. L. Hyland, Jonathan M. Manning, Stephen F. McLaughlin, Heather E. Peckham, Onur Sakarya, Yongming A. Sun, Eric F. Tsung, Mark A. Batzer, Miriam K. Konkel, Jerilyn A. Walker, Ralf Sudbrak, Marcus W. Albrecht, Vyacheslav S. Amstislavskiy, Ralf Herwig, Dimitri V. Parkhomchuk, Stephen T. Sherry, 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, Gil A. McVean, Adam Auton, Zamin Iqbal, Gerton Lunter, Jonathan L. Marchini, Loukas Moutsianas, Simon Myers, Afidalina Tumian, Brian Desany, James Knight, Roger Winer, David W. Craig, Steve 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, Gonçalo R. Abecasis, 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. Cenk Sahinalp, Peter H. Sudmant, Elaine R. Mardis, Ken Chen, Asif Chinwalla, Li Ding, Daniel C. Koboldt, Mike D. McLellan, David Dooling, George Weinstock, John W. Wallis, Michael C. Wendl, Qunyuan Zhang, Richard M. Durbin, Cornelis A. Albers, Qasim Ayub, Senduran Balasubramaniam, Jeffrey C. Barrett, David M. Carter, Yuan Chen, Donald F. Conrad, Petr Danecek, Emmanouil T. Dermitzakis, Min Hu, Ni Huang, Matt E. Hurles, Hanjun Jin, Luke Jostins, Thomas M. Keane, Si Quang Le, Sarah Lindsay, Quan Long, Daniel G. MacArthur, Stephen B. Montgomery, Leopold Parts, James Stalker, Chris Tyler-Smith, Klaudia Walter, Yujun Zhang, Mark B. Gerstein, Michael Snyder, Alexej Abyzov, Suganthi Balasubramanian, Robert Bjornson, Jiang Du, Fabian Grubert, Lukas Habegger, Rajini Haraksingh, Justin Jee, Ekta Khurana, Hugo Y. K. Lam, Jing Leng, Xinmeng Jasmine Mu, Alexander E. Urban, Zhengdong Zhang, Yingrui Li, Ruibang Luo, Gabor T. Marth, Erik P. Garrison, Deniz Kural, Aaron R. Quinlan, Chip Stewart, Michael P. Stromberg, Alistair N. Ward, Jiantao Wu, Charles Lee, Ryan E. Mills, Xinghua Shi, Steven A. McCarroll, Eric Banks, Mark A. DePristo, Robert E. Handsaker, Chris Hartl, Joshua M. Korn, Heng Li, James C. Nemesh, Jonathan Sebat, Vladimir Makarov, Kenny Ye, Seungtai C. Yoon, Jeremiah Degenhardt, Mark Kaganovich, Laura Clarke, Richard E. Smith, Xiangqun Zheng-Bradley, Jan O. Korbel, Sean Humphray, R. Keira Cheetham, Michael Eberle, Scott Kahn, Lisa Murray, Kai Ye, Francisco M. De La Vega, Yutao Fu, Heather E. Peckham, Yongming A. Sun, Mark A. Batzer, Miriam K. Konkel, Jerilyn A. Walker, Chunlin Xiao, Zamin Iqbal, Brian Desany, Tom Blackwell, Matthew Snyder, Jinchuan Xing, Evan E. Eichler, Gozde Aksay, Can Alkan, Iman Hajirasouliha, Fereydoun Hormozdiari, Jeffrey M. Kidd, Ken Chen, Asif Chinwalla, Li Ding, Mike D. McLellan, John W. Wallis, Matt E. Hurles, Donald F. Conrad, Klaudia Walter, Yujun Zhang, Mark B. Gerstein, Michael Snyder, Alexej Abyzov, Jiang Du, Fabian Grubert, Rajini Haraksingh, Justin Jee, Ekta Khurana, Hugo Y. K. Lam, Jing Leng, Xinmeng Jasmine Mu, Alexander E. Urban, Zhengdong Zhang, Richard A. Gibbs, Matthew Bainbridge, Danny Challis, Cristian Coafra, Huyen Dinh, Christie Kovar, Sandy Lee, Donna Muzny, Lynne Nazareth, Jeff Reid, Aniko Sabo, Fuli Yu, Jin Yu, Gabor T. Marth, Erik P. Garrison, Amit Indap, Wen Fung Leong, Aaron R. Quinlan, Chip Stewart, Alistair N. Ward, Jiantao Wu, Kristian Cibulskis, Tim J. Fennell, Stacey B. Gabriel, Kiran V. Garimella, Chris Hartl, Erica Shefler, Carrie L. Sougnez, Jane Wilkinson, Andrew G. Clark, Simon Gravel, Fabian Grubert, Laura Clarke, Paul Flicek, Richard E. Smith, Xiangqun Zheng-Bradley, Stephen T. Sherry, Hoda M. Khouri, Justin E. Paschall, Martin F. Shumway, Chunlin Xiao, Gil A. McVean, Sol J. Katzman, Gonçalo R. Abecasis, Tom Blackwell, Elaine R. Mardis, David Dooling, Lucinda Fulton, Robert Fulton, Daniel C. Koboldt, Richard M. Durbin, Senduran Balasubramaniam, Allison Coffey, Thomas M. Keane, Daniel G. MacArthur, Aarno Palotie, Carol Scott, James Stalker, Chris Tyler-Smith, Mark B. Gerstein, Suganthi Balasubramanian, Aravinda Chakravarti, Bartha M. Knoppers, Gonçalo R. Abecasis, Carlos D. Bustamante, Neda Gharani, Richard A. Gibbs, Lynn Jorde, Jane S. Kaye, Alastair Kent, Taosha Li, Amy L. McGuire, Gil A. McVean, Pilar N. Ossorio, Charles N. Rotimi, Yeyang Su, Lorraine H. Toji, Chris Tyler-Smith, Lisa D. Brooks, Adam L. Felsenfeld, Jean E. McEwen, Assya Abdallah, Christopher R. Juenger, Nicholas C. Clemm, Francis S. Collins, Audrey Duncanson, Eric D. Green, Mark S. Guyer, Jane L. Peterson, Alan J. Schafer, Gonçalo R. Abecasis, David L. Altshuler, Adam Auton, Lisa D. Brooks, Richard M. Durbin, Richard A. Gibbs, Matt E. Hurles, Gil A. McVean

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(-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. More... »

PAGES

1061

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  • Journal

    TITLE

    Nature

    ISSUE

    7319

    VOLUME

    467

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature09534

    DOI

    http://dx.doi.org/10.1038/nature09534

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010608717

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20981092


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