An integrated map of genetic variation from 1,092 human genomes

作者：Gil A. McVean, Peter Donnelly, Anjali Gupta-Hinch, Zamin Iqbal, Iain Mathieson, Andy Rimmer, Dionysia K. Xifara, Angeliki Kerasidou, Claire Churchhouse, Olivier Delaneau, Stacey B. Gabriel, Eric S. Lander, David Altshuler, Namrata Gupta, Eric Banks, Gaurav Bhatia, Mauricio O. Carneiro, Guillermo del Angel, G Genovese, Robert E. Handsaker, Chris Hartl, S A McCarroll, James Nemesh, Ryan Poplin, S. F. Schaffner, Khalid Shakir, Sharon R. Grossman, Shervin Tabrizi, Ridhi Tariyal, H Li, Mark A. DePristo, David Reich, M. E. Hurles, Senduran Balasubramaniam, John Burton, Petr Danecek, Thomas Keane, Anja Kolb-Kokocinski, Shane McCarthy, James Stalker, Michael Quail, Qasim Ayub, Yuan Chen, Coffey Ak, Vincenza Colonna, Ni Huang, Luke Jostins, Aylwyn Scally, Klaudia Walter, Yali Xue, Yujun Zhang, Ben Blackburne, Sarah Lindsay, Zemin Ning, Adam Frankish, J Harrow, Richard Durbin, C Tyler-Smith, Abecasis Gb, Paul Anderson, Tom Blackwell, Fabio Busonero, Christian Fuchsberger, Goo Jun, Andrea Maschio, Eleonora Porcu, Carlo Sidore, Adrian Tan, Mary Kate Trost, Kang Hc, David R. Bentley, Grocock Rj, Sean Humphray, Terena James, Zoya Kingsbury, Markus Bauer, R. Keira Cheetham, Tony Cox, Michael Eberle, Lisa Murray, Richard Shaw, A Chakravarti, Andrew G. Clark, Alon Keinan, Juan L. Rodriguez-Flores, Francisco M. De La Vega, Jeremiah Degenhardt, Evan E. Eichler, P Flicek, Laura Clarke, Rasko Leinonen, RICHARD E. SMITH, Xiangqun Zheng-Bradley, Kathryn Beal, Fiona Cunningham, Javier Herrero, William McLaren, Graham R. S. Ritchie, JA Barker, Gavin Kelman, Eugene Kulesha, Rajesh Radhakrishnan, Asier Roa, Dmitriy Smirnov, Ian Streeter, Iliana Toneva, Brendan Vaughan, Richard A. Gibbs, Huyen Dinh, Christie Kovar, Sandra Lee, Lora Lewis, Muzny Dm, Jeff Reid, M Wang, Matthew Bainbridge, Danny Challis, Uday S. Evani, James Lu, Uma Nagaswamy, Aniko Sabo, Yue Wang, Jin Yu, Fuli Yu, G. Fowler, Walker Hale, Divya Kalra, Ed Green, Bartha M. Knoppers, J K Korbel, Tobias Rausch, Adrian M. Stütz, Charles Lee, Lauren Griffin, Chih-Heng Hsieh, Ryan E. Mills, Xinghua Shi, Marcin von Grotthuss, Chengsheng Zhang, Hans Lehrach, Vyacheslav Amstislavskiy, Matthias Lienhard, Florian Mertes, Marc Sultan, Bernd Timmermann, Yaspo Ml, Ralf Herwig, Ralf Sudbrak, Elaine R. Mardis, Wilson Rk, L L Fulton, R J Fulton, George M. Weinstock, Asif Chinwalla, Li Ding, David Dooling, Daniel C. Koboldt, Michael D. McLellan, John W. Wallis, Michael C. Wendl, Qunyuan Zhang, Gábor Marth, Erik Garrison, Deniz Kural, Wan-Ping Lee, Wen Fung Leong, Alistair Ward, Jiantao Wu, Mengyao Zhang, Deborah A. Nickerson, Can Alkan, Fereydoun Hormozdiari, Arthur Ko, Peter H. Sudmant, Jeanette P. Schmidt, Christopher J. Davies, Jeremy Gollub, Teresa Webster, Brant Wong, Yiping Zhan, Stephen T. Sherry, Chunlin Xiao, Deanna Church, Victor Ananiev, Zinaida Belaia, Dimitriy Beloslyudtsev, Nathan Bouk, Chao Chen, Cohen Rm, Charles Cook, John Garner, Timothy Hefferon, Mikhail Kimelman, Chunlei Liu, John Lopez, Peter Meric, Yuri Ostapchuk, Lon Phan, Sergiy Ponomarov, Valerie Schneider, Shekhtman Em, Karl Sirotkin, Douglas Slotta, Haitao Zhang, Yi-Xiang Wang, Xiaodong Fang, Xiaosen Guo, Min Jian, Hui Jiang, Xin Jin, Guoqing Li, Jingxiang Li, Yingrui Li, Zhuo Li, Xiao Liu, Yao Lu, Xuedi Ma, Zhe Su, Shuaishuai Tai, Meifang Tang, Bo Wang, Guangbiao Wang, Honglong Wu, Renhua Wu, Ye Yin, Wei Zhang, Jiao Zhao, Meiru Zhao, Xiaole Zheng, Yan Zhou, Lachlan Coin, Li Fang, Qibin Li, Zhenyu Li, Haoxiang Lin, Binghang Liu, Ruibang Luo, Nan Qin, Haojing Shao, Bingqiang Wang, Yinlong Xie, Yuehua Chen, Chang Yu, Fan Zhang, Hancheng Zheng, Hongmei Zhu, Hongyu Cai, Hongzhi Cao, Yeyang Su, Zhongming Tian, Yuhong Wang, Huanming Yang, L Yang, Jiayong Zhu, Cai Zhi Ming, Marcus W. Albrecht, Tatiana Borodina, Adam Auton, Jayon Lihm, Vladimir Makarov, Wook Kim, Ki Cheol Kim, Srikanth Gottipati, D. Jones, Edward V. Ball, Stenson Pd, Bret Barnes, Scott Kahn, Miriam K. Konkel, Jerilyn A. Walker, Monkol Lek, Gravel, Eimear E. Kenny, Jeffrey M. Kidd, Phil Lacroute, Brian K. Maples, Andres Moreno-Estrada, Fouad Zakharia, Bustamante Cd, Brenna Henn, Karla Sandoval, Jake Byrnes, Yael Baran, Alexis Christoforides, Tyler Izatt, Ahmet Kurdoglu, Shripad Sinari, Nils Homer, Kevin Squire, Vineet Bafna, Kenny Ye, Christopher R. Gignoux, E G Burchard, Sol Katzman, W. James Kent, B Howie, Andrés Ruiz-Linares, Tuuli Lappalainen, Xinyue Liu, Ankit Maroo, Luke J. Tallon, Leslie P. Michelson, Andrea Angius, Francesco Cucca, Serena Sanna, Abigail Bigham, Chris Jones, Fred Reinier, Yun Li, Robert Lyons, David Schlessinger, Alan Hodgkinson, Juan C. Martínez-Cruzado, Tarás K. Oleksyk, Xiaoming Liu, Momiao Xiong, David Witherspoon, Jorde Lb, Jinchuan Xing, Iman Hajirasouliha, Ken Chen, Cornelis A. Albers, Alexej Abyzov, Jieming Chen, Yao Fu, Lukas Habegger, Arif O. Harmanci, Xinmeng Jasmine Mu, Cristina Sisu, Suganthi Balasubramanian, Mike Jin, E Khurana, Declan Clarke, Jacob J. Michaelson, Chris O’Sullivan, Barnes Kc, Christine Beiswanger, Neda Gharani, Lorraine H. Toji, Jane Kaye, Alastair Kent, Rasika Mathias, Pilar N. Ossorio, Michael Parker, Charles N. Rotimi, Charmaine D. Royal, Sarah Tishkoff, Marc Via, Walter Bodmer, Gabriel Bedoya, Gao Yang, Chu Jia You, Leticia García, Alberto Órfão, Julie Dutil, Lisa D. Brooks, Adam L. Felsenfeld, Jean E. McEwen, Nicholas C. Clemm, Mark S. Guyer, Jane L. Peterson, Audrey Duncanson, Michael Dunn · 发表于：Nature · 年份：2012 · DOI：10.1038/nature11632 · 被引用次数：8271 · 研究领域：Genetic Associations and Epidemiology、Genomics and Rare Diseases、Genetic Mapping and Diversity in Plants and Animals

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. This report from the 1000 Genomes ...