A map of human genome variation from population-scale sequencing

作者：Richard Durbin, John Burton, David M. Carter, Carol Churcher, Coffey Ak, Anthony Cox, A Palotie, Michael Quail, Tom Skelly, James Stalker, Harold P. Swerdlow, Daniel Turner, Qasim Ayub, Senduran Balasubramaniam, Jeffrey C. Barrett, Yuan Chen, Donald F. Conrad, Petr Danecek, Min Hu, Ni Huang, Matt Hurles, Luke Jostins, Thomas Keane, Si Quang Le, Sarah Lindsay, Quan Long, Daniel G. MacArthur, Leopold Parts, C Tyler-Smith, Klaudia Walter, Yali Xue, Yujun Zhang, Allison Coffey, Carol Scott, Stacey B. Gabriel, Eric S. Lander, David Altshuler, Lauren Ambrogio, Toby Bloom, Kristian Cibulskis, Tim Fennell, David B. Jaffe, Erica Shefler, Carrie Sougnez, Aaron D. Ball, Eric Banks, Kiran Garimella, Sharon R. Grossman, Robert E. Handsaker, Matt Hanna, Chris Hartl, Andrew Kernytsky, Joshua M. Korn, H Li, Jared R. Maguire, S A McCarroll, Aaron McKenna, James Nemesh, Anthony A. Philippakis, Ryan Poplin, Manuel A. Rivas, Sabeti Pc, S. F. Schaffner, Ilya Shlyakhter, Mark A. DePristo, Jane Wilkinson, Paul Anderson, Tom Blackwell, Wei Chen, Jun Ding, Hyun Min Kang, Carlo Sidore, Matthew Snyder, Xiaowei Zhan, S Zollner, Gonçalo R. Abecasis, David R. Bentley, Ñ Lauren Gormley, Sean Humphray, Zoya Kingsbury, Paula Kokko‐Gonzales, Jennifer Stone, R. Keira Cheetham, Tony Cox, Michael Eberle, Terena James, Scott Kahn, Lisa Murray, A Chakravarti, Andrew G. Clark, Jeremiah Degenhardt, Collins Fs, Francisco M. De La Vega, Fiona Hyland, Onur Sakarya, Yongming A. Sun, Peter Donnelly, Gil A. McVean, Adam Auton, Zamin Iqbal, Gerton Lunter, Jonathan L. Marchini, Simon Myers, Michael Egholm, Paul Flicek, Fiona Cunningham, Javier Herrero, Stephen Keenen, Eugene Kulesha, Rasko Leinonen, William McLaren, Rajesh Radhakrishnan, RICHARD E. SMITH, Vadim Zalunin, Xiangqun Zheng-Bradley, Richard A. Gibbs, David Deiros, Mike Metzker, Muzny Dm, Jeff Reid, David A. Wheeler, Matthew Bainbridge, Danny Challis, Aniko Sabo, Fuli Yu, Jin Yu, Cristian Coafra, Huyen Dinh, Christie Kovar, Sandy Lee, Lynne Nazareth, Bartha M. Knoppers, Hans Lehrach, Tatiana Borodina, Alexey N. Davydov, Peter Marquardt, Florian Mertes, Wilfiried Nietfeld, Aleksey V. Soldatov, Bernd Timmermann, Marius Tolzmann, Marcus W. Albrecht, Vyacheslav Amstislavskiy, Ralf Herwig, Dimitri V. Parkhomchuk, Elaine R. Mardis, Wilson Rk, David Dooling, L L Fulton, R J Fulton, George Weinstock, Ken Chen, Asif Chinwalla, Li Ding, Daniel C. Koboldt, Mike D. McLellan, John W. Wallis, Michael C. Wendl, Qunyuan Zhang, Loukas Moutsianas, Afidalina Tumian, Deborah A. Nickerson, Gozde Aksay, Jeffrey M. Kidd, Alan J. Schafer, Audrey Duncanson, Stephen T. Sherry, Richa Agarwala, Hoda Khouri, Aleksandr Morgulis, Justin Paschall, Lon D. Phan, Kirill E. Rotmistrovsky, Robert D. Sanders, Martin Shumway, Chunlin Xiao, Yi-Xiang Wang, Min Jian, Guoqing Li, Ruiqiang Li, Huiqing Liang, Geng Tian, Bo Wang, Yi-Xiang Wang, W J Wang, Huanming Yang, Xi Zhang, Huisong Zheng, Xiaodong Fang, Xiaosen Guo, Yingrui Li, Ruibang Luo, Shuaishuai Tai, Honglong Wu, Hancheng Zheng, Xiaole Zheng, Yan Zhou, Taosha Li, Yeyang Su, Gina L. Costa, Jeffry K. Ichikawa, Clarence Lee, Yutao Fu, Jonathan M. Manning, Stephen F. McLaughlin, Heather E. Peckham, Eric F. Tsung, Andreas Dahl, Philip Rosenstiel, Stefan Schreiber, Jason Affourtit, Ashworth Dn, 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, Riches Dj, Wanmin Song, Cynthia Turcotte, Shally Wang, James Knight, Roger Winer, Anniek De Witte, Shane Giles, Erik Garrison, Amit Indap, Deniz Kural, Wan-Ping Lee, Wen Fung Leong, Chip Stewart, Alistair Ward, Jiantao Wu, Weichun Huang, Aaron R. Quinlan, Michael P. Strömberg, Ryan E. Mills, Xinghua Shi, Brian L. Browning (9548786), Alkes Price, Edward V. Ball, Matthew Mort, Andrew D. Phillips, Stenson Pd, Vladimir Makarov, Seungtai C. Yoon, Kenny Ye, Fabian Grubert, Hugo Y. K. Lam, A Urban, Mark Kaganovich, Gravel, Adrian M. Stütz, J K Korbel, Kai Ye, Miriam K. Konkel, Jerilyn A. Walker, Steve M. Beckstrom-Sternberg, Alexis Christoforides, Ahmet Kurdoglu, John V. Pearson, Shripad Sinari, Waibhav D. Tembe, Angie S. Hinrichs, Sol Katzman, Andrew Kern, Robert M. Kuhn, Molly Przeworski, Ryan D. Hernandez, B Howie, Joanna L. Kelley, S. Cord Melton, William O. Cookson, Miriam F. Moffatt, Mark Lathrop, Liming Liang, Paul Scheet, Ferrán Casals, Youssef Idaghdour, Keebler Js, Eric A. Stone, Martine Zilversmit, Jinchuan Xing, Jorde Lb, Evan E. Eichler, Can Alkan, Iman Hajirasouliha, Fereydoun Hormozdiari, Cornelis A. Albers, E. T. Dermitzakis, Stephen B. Montgomery, Hanjun Jin, Alexej Abyzov, Lukas Habegger, Rajini Haraksingh, Justin Jee, Jing Leng, Xinmeng Jasmine Mu, Robert Bjornson, Jiang Du, Suganthi Balasubramanian, E Khurana, Zhengdong Zhang, Neda Gharani, Lorraine H. Toji, Jane Kaye, Alastair Kent, Amy L. McGuire, Pilar N. Ossorio, Charles N. Rotimi, Lisa D. Brooks, Adam L. Felsenfeld, Jean E. McEwen, Nicholas C. Clemm, Mark S. Guyer, Jane L. Peterson, Assya Abdallah, Christopher R. Juenger, Ed Green, Reed A. Cartwright · 发表于：Nature · 年份：2010 · DOI：10.1038/nature09534 · 被引用次数：8126 · 研究领域：Genomics and Rare Diseases、Genetic Associations and Epidemiology、Genomic variations and chromosomal abnormalities

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 na...