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

David M. Altshuler, Richard M. Durbin, Gonçalo R. Abecasis, David R. Bentley, Aravinda Chakravarti, Andrew G. Clark, Peter Donnelly, Evan E. Eichler, Paul Flicek, Stacey B. Gabriel, Richard A. Gibbs, Eric D. Green, Matthew E. Hurles, Bartha M. Knoppers, Jan O. Korbel, Eric S. Lander, Charles Lee, Hans Lehrach, Elaine R. Mardis, Gabor T. MarthGil A. McVean, Deborah A. Nickerson, Jeanette P. Schmidt, Stephen T. Sherry, Jun Wang, Richard K. Wilson, Huyen Dinh, Christie Kovar, Sandra Lee, Lora Lewis, Donna Muzny, Jeff Reid, Min 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, Wenwei Zhang, Jiao Zhao, Meiru Zhao, Xiaole Zheng, Yan Zhou, Namrata Gupta, Laura Clarke, Rasko Leinonen, Richard E. Smith, Xiangqun Zheng-Bradley, Russell Grocock, Sean Humphray, Terena James, Zoya Kingsbury, Ralf Sudbrak, Marcus W. Albrecht, Vyacheslav S. Amstislavskiy, Tatiana A. Borodina, Matthias Lienhard, Florian Mertes, Marc Sultan, Bernd Timmermann, Marie Laure Yaspo, Lucinda Fulton, Robert Fulton, George M. Weinstock, Senduran Balasubramaniam, John Burton, Petr Danecek, Thomas M. Keane, Anja Kolb-Kokocinski, Shane McCarthy, James Stalker, Michael Quail, Christopher J. Davies, Jeremy Gollub, Teresa Webster, Brant Wong, Yiping Zhan, Adam Auton, Fuli Yu, Matthew Bainbridge, Danny Challis, Uday S. Evani, James Lu, Uma Nagaswamy, Aniko Sabo, Yi Wang, Jin Yu, Lachlan J.M. Coin, Lin Fang, Qibin Li, Zhenyu Li, Haoxiang Lin, Binghang Liu, Ruibang Luo, Nan Qin, Haojing Shao, Bingqiang Wang, Yinlong Xie, Chen Ye, Chang Yu, Fan Zhang, Hancheng Zheng, Hongmei Zhu, Erik P. Garrison, Deniz Kural, Wan Ping Lee, Wen Fung Leong, Alistair N. Ward, Jiantao Wu, Mengyao Zhang, Lauren Griffin, Chih Heng Hsieh, Ryan E. Mills, Xinghua Shi, Marcin Von Grotthuss, Chengsheng Zhang, Mark J. Daly, Mark A. Depristo, Eric Banks, Gaurav Bhatia, Mauricio O. Carneiro, Guillermo Del Angel, Giulio Genovese, Robert E. Handsaker, Chris Hartl, Steven A. McCarroll, James C. Nemesh, Ryan E. Poplin, Stephen F. Schaffner, Khalid Shakir, Seungtai C. Yoon, Jayon Lihm, Vladimir Makarov, Hanjun Jin, Wook Kim, Ki Cheol Kim, Tobias Rausch, Kathryn Beal, Fiona Cunningham, Javier Herrero, William M. McLaren, Graham R.S. Ritchie, Srikanth Gottipati, Alon Keinan, Juan L. Rodriguez-Flores, Pardis C. Sabeti, Sharon R. Grossman, Shervin Tabrizi, Ridhi Tariyal, David N. Cooper, Edward V. Ball, Peter D. Stenson, Bret Barnes, Markus Bauer, R. Keira Cheetham, Tony Cox, Michael Eberle, Scott Kahn, Lisa Murray, John Peden, Richard Shaw, Kai Ye, Mark A. Batzer, Miriam K. Konkel, Jerilyn A. Walker, Daniel G. MacArthur, Monkol Lek, Ralf Herwig, Mark D. Shriver, Carlos D. Bustamante, Jake K. Byrnes, Francisco M. De La Vega, Simon Gravel, Eimear E. Kenny, Jeffrey M. Kidd, Brian K. Maples, Andres Moreno-Estrada, Fouad Zakharia, Eran Halperin, Yael Baran, David W. Craig, Alexis Christoforides, Nils Homer, Tyler Izatt, Ahmet A. Kurdoglu, Shripad A. Sinari, Kevin Squire, Chunlin Xiao, Jonathan Sebat, Vineet Bafna, Kenny Ye, Esteban G. Burchard, Ryan D. Hernandez, Christopher R. Gignoux, David Haussler, Sol J. Katzman, W. James Kent, Bryan Howie, Andres Ruiz-Linares, Emmanouil T. Dermitzakis, Tuuli Lappalainen, Scott E. Devine, Xinyue Liu, Ankit Maroo, Luke J. Tallon, Jeffrey A. Rosenfeld, Leslie P. Michelson, Hyun Min Kang, Paul Anderson, Andrea Angius, Abigail Bigham, Tom Blackwell, Fabio Busonero, Francesco Cucca, Christian Fuchsberger, Chris Jones, Goo Jun, Yun Li, Robert Lyons, Andrea Maschio, Eleonora Porcu, Fred Reinier, Serena Sanna, David Schlessinger, Carlo Sidore, Adrian Tan, Mary Kate Trost, Philip Awadalla, Alan Hodgkinson, Gerton Lunter, Jonathan L. Marchini, Simon Myers, Claire Churchhouse, Olivier Delaneau, Anjali Gupta-Hinch, Zamin Iqbal, Iain Mathieson, Andy Rimmer, Dionysia K. Xifara, Taras K. Oleksyk, Yunxin Fu, Xiaoming Liu, Momiao Xiong, Lynn Jorde, David Witherspoon, Jinchuan Xing, Brian L. Browning, Can Alkan, Iman Hajirasouliha, Fereydoun Hormozdiari, Arthur Ko, Peter H. Sudmant, Ken Chen, Asif Chinwalla, Li Ding, David Dooling, Daniel C. Koboldt, Michael D. McLellan, John W. Wallis, Michael C. Wendl, Qunyuan Zhang, Chris Tyler-Smith, Cornelis A. Albers, Qasim Ayub, Yuan Chen, Alison J. Coffey, Vincenza Colonna, Ni Huang, Luke Jostins, Heng Li, Aylwyn Scally, Klaudia Walter, Yali Xue, Yujun Zhang, Mark B. Gerstein, Alexej Abyzov, Suganthi Balasubramanian, Jieming Chen, Declan Clarke, Yao Fu, Lukas Habegger, Arif O. Harmanci, Mike Jin, Ekta Khurana, Xinmeng Jasmine Mu, Cristina Sisu, Jeremiah Degenhardt, Adrian M. Stütz, R. Keira Cheetham, Deanna Church, Jacob J. Michaelson, Ben Blackburne, Sarah J. Lindsay, Zemin Ning, Adam Frankish, Jennifer Harrow, Xinmeng Jasmine Mu, Gerald Fowler, Walker Hale, Divya Kalra, Jonathan Barker, Gavin Kelman, Eugene Kulesha, Rajesh Radhakrishnan, Asier Roa, Dmitriy Smirnov, Ian Streeter, Iliana Toneva, Brendan Vaughan, Victor Ananiev, Zinaida Belaia, Dimitriy Beloslyudtsev, Nathan Bouk, Chao Chen, Robert Cohen, Charles Cook, John Garner, Timothy Hefferon, Mikhail Kimelman, Chunlei Liu, John Lopez, Peter Meric, Chris O'Sullivan, Yuri Ostapchuk, Lon Phan, Sergiy Ponomarov, Valerie Schneider, Eugene Shekhtman, Karl Sirotkin, Douglas Slotta, Hua Zhang, Kathleen C. Barnes, Christine Beiswanger, Hongyu Cai, Hongzhi Cao, Neda Gharani, Brenna Henn, Danielle Jones, Jane S. Kaye, Alastair Kent, Angeliki Kerasidou, Rasika Mathias, Pilar N. Ossorio, Michael Parker, David Reich, Charles N. Rotimi, Charmaine D. Royal, Karla Sandoval, Yeyang Su, Zhongming Tian, Sarah Tishkoff, Lorraine H. Toji, Marc Via, Yuhong Wang, Huanming Yang, Ling Yang, Jiayong Zhu, Walter Bodmer, Gabriel Bedoya, Cai Zhi Ming, Gao Yang, Chu Jia You, Leena Peltonen, Andres Garcia-Montero, Alberto Orfao, Julie Dutil, Juan C. Martinez-Cruzado, Lisa D. Brooks, Adam L. Felsenfeld, Jean E. McEwen, Nicholas C. Clemm, Audrey Duncanson, Michael Dunn, Mark S. Guyer, Jane L. Peterson, Phil Lacroute

Research output: Contribution to journalArticle

4750 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)56-65
Number of pages10
JournalNature
Volume491
Issue number7422
DOIs
StatePublished - Nov 1 2012

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'An integrated map of genetic variation from 1,092 human genomes'. Together they form a unique fingerprint.

  • Cite this

    Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., Clark, A. G., Donnelly, P., Eichler, E. E., Flicek, P., Gabriel, S. B., Gibbs, R. A., Green, E. D., Hurles, M. E., Knoppers, B. M., Korbel, J. O., Lander, E. S., Lee, C., Lehrach, H., Mardis, E. R., ... Lacroute, P. (2012). An integrated map of genetic variation from 1,092 human genomes. Nature, 491(7422), 56-65. https://doi.org/10.1038/nature11632