A global reference for human genetic variation

Authors: Corresponding authors, Adam Auton, Gonçalo R. Abecasis, David M. Altshuler, Richard 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, Gábor Marth, Gil A. McVean, Deborah A. Nickerson, Jeanette P. Schmidt, Stephen T. Sherry, Jun Wang, Richard K. Wilson, Production group, Richard A. Gibbs, Eric Boerwinkle, HarshaVardhan Doddapaneni, Yi Han, Viktoriya Korchina, Christie Kovar, Sandra Lee, Donna M. Muzny, Jeffrey G. Reid, Yiming Zhu, BGI-Shenzhen, Jun Wang, Yuqi Chang, Qiang Feng, Xiaodong Fang, Xiaosen Guo, Min Jian, Hui Jiang, Xin Jin, Tianming Lan, Guoqing Li, Jingxiang Li, Yingrui Li, Shengmao Liu, Xiao Liu, Yao Lu, Xuedi Ma, Meifang Tang, Bo Wang, Guangbiao Wang, Honglong Wu, Renhua Wu, Xun Xu, Ye Yin, Dandan Zhang, Wenwei Zhang, Jiao Zhao, Meiru Zhao, Xiaole Zheng, Eric S. Lander, David M. Altshuler, Stacey Gabriel, Namrata Gupta, Neda Gharani, Lorraine H. Toji, Norman P. Gerry, Alissa Resch, Paul Flicek, Jonathan Barker, Laura Clarke, Laurent Gil, Sarah Hunt, Gavin Kelman, Eugene Kulesha, Rasko Leinonen, William McLaren, Rajesh Radhakrishnan, Asier Roa, Dmitriy Smirnov, Richard E. Smith, Ian Streeter, Anja Thormann, Iliana Toneva, Brendan Vaughan, Xiangqun Zheng-Bradley, Illumina, David R. Bentley, Russell Grocock, Sean Humphray, Terena James, Zoya Kingsbury, Hans Lehrach, Ralf Sudbrak, Marcus W. Albrecht, Vyacheslav S. Amstislavskiy, Tatiana Borodina, Matthias Lienhard, Florian Mertes, Marc Sultan, Bernd Timmermann, Marie‐Laure Yaspo, Elaine R. Mardis, Richard K. Wilson, Lucinda Fulton, Robert S. Fulton, Stephen T. Sherry, Victor Ananiev, Zinaida Belaia, Dimitriy Beloslyudtsev, Nathan Bouk, Chao Chen, Deanna M. Church, 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, Valérie Schneider, Eugene Shekhtman, Karl Sirotkin, Douglas J. Slotta, Hua Zhang, Gil A. McVean, Richard Durbin, Senduran Balasubramaniam, John H. Burton, Petr Danecek, Thomas Keane, Anja Kolb‐Kokocinski, Shane McCarthy, James Stalker, Michael A. Quail, Analysis group, Affymetrix, Jeanette P. Schmidt, Christopher J. Davies, Jeremy Gollub, Teresa Webster, Brant Wong, Yiping Zhan, Adam Auton, Christopher Campbell, Yu Kong, Anthony Marcketta, Richard A. Gibbs, Fuli Yu, Lilian Antunes, Matthew N. Bainbridge, Donna Muzny, Aniko Sabo, Zhuoyi Huang, BGI-Shenzhen, Jun Wang, Lachlan Coin, Lin Fang, Xiaosen Guo, Xin Jin, Guoqing Li, Qibin Li, Yingrui Li, Zhenyu Li, Haoxiang Lin, Binghang Liu, Ruibang Luo, Haojing Shao, Yinlong Xie, Chen Ye, Chang Yu, Fan Zhang, Hancheng Zheng, Hongmei Zhu, Can Alkan, Elif Dal, Fatma Kahveci, Gabor T. Marth, Erik Garrison, Deniz Kural, Wan-Ping Lee, Wen Fung Leong, Michael P. Strömberg, Alistair Ward, Jiantao Wu, Mengyao Zhang, Mark J. Daly, Mark A. DePristo, Robert E. Handsaker, David M. Altshuler, Eric Banks, Gaurav Bhatia, Guillermo del Angel, Stacey B. Gabriel, Giulio Genovese, Namrata Gupta, Heng Li, Seva Kashin, Eric S. Lander, Steven A. McCarroll, James Nemesh, Ryan Poplin, Seungtai Yoon, Jayon Lihm, Vladimir Makarov, Andrew G. Clark, Srikanth Gottipati, Alon Keinan, Juan L. Rodríguez-Flores, Jan O. Korbel, Tobias Rausch, Markus H. Fritz, Adrian M. Stütz, Paul Flicek, Kathryn Beal, Laura Clarke, Avik Datta, Javier Herrero, William McLaren, Graham R. S. Ritchie, Richard E. Smith, Daniel R. Zerbino, Xiangqun Zheng-Bradley, Pardis C. Sabeti, Ilya Shlyakhter, S. F. Schaffner, Joseph J. Vitti, Human Gene Mutation Database, D.N. Cooper, Edward V. Ball, Peter D. Stenson, Illumina, David R. Bentley, Bret Barnes, Markus Bauer, R. Keira Cheetham, Anthony J. Cox, Michael Eberle, Sean Humphray, Scott Kahn, Lisa Murray, John F. Peden, Richard J. Shaw, Eimear E. Kenny, Mark A. Batzer, Miriam K. Konkel, Jerilyn A. Walker, Daniel G. MacArthur, Monkol Lek, Ralf Sudbrak, Vyacheslav S. Amstislavskiy, Ralf Herwig, Elaine R. Mardis, Li Ding, Daniel C. Koboldt, David E. Larson, Kai Ye, Simon Gravel, Anand Swaroop, Emily Y. Chew, Tuuli Lappalainen, Yaniv Erlich, Melissa Gymrek, Thomas Frederick Willems, Jared T. Simpson, Mark D. Shriver, Jeffrey Rosenfeld, Carlos D. Bustamante, Stephen B. Montgomery, Francisco M. De La Vega, Jake Byrnes, Andrew Carroll, Marianne K. DeGorter, Phil Lacroute, Brian K. Maples, Alicia R. Martin, Andres Moreno-Estrada, Suyash Shringarpure, Fouad Zakharia, Eran Halperin, Yael Baran, Charles Lee, Eliza Cerveira, Jaeho Hwang, Ankit Malhotra, Dariusz Plewczyński, Kamen Radew, Mallory Romanovitch, Chengsheng Zhang, Thermo Fisher Scientific, Fiona Hyland, David W. Craig, Alexis Christoforides, Nils Homer, Tyler Izatt, Ahmet Kurdoglu, Shripad Sinari, Kevin Squire, Stephen T. Sherry, Chunlin Xiao, Jonathan Sebat, Danny Antaki, Madhusudan Gujral, Amina Noor, Kenny Ye, Esteban G. Burchard, Ryan D. Hernandez, Christopher R. Gignoux, David Haussler, Sol Katzman, Wm. Kent, Bryan Howie, Andrés Ruiz‐Linares, Emmanouil T. Dermitzakis, Scott E. Devine, Gonçalo R. Abecasis, Hyun Min Kang, Jeffrey M. Kidd, Tom Blackwell, Sean Caron, Wei Chen, Sarah Emery, Lars G. Fritsche, Christian Fuchsberger, Goo Jun, Bingshan Li, Robert Lyons, Chris Scheller, Carlo Sidore, Shiya Song, Elżbieta Śliwerska, Daniel Taliun, Adrian Tan, Ryan Welch, Mary Kate Wing, Xiaowei Zhan, Philip Awadalla, Alan Hodgkinson, Yun Li, Xinghua Shi, Andrew Quitadamo, Gerton Lunter, Gil McVean, Jonathan L. Marchini, Simon Myers, Claire Churchhouse, Olivier Delaneau, Anjali Gupta Hinch, Warren W. Kretzschmar, Zamin Iqbal, Iain Mathieson, Androniki Menelaou, Andy Rimmer, Dionysia K. Xifara, Tarás K. Oleksyk, Yun‐Xin Fu, Xiaoming Liu, Momiao Xiong, Lynn B. Jorde, David J. Witherspoon, Jinchuan Xing, Evan E. Eichler, Brian L. Browning, Sharon R. Browning, Fereydoun Hormozdiari, Peter H. Sudmant, Ekta Khurana, Richard Durbin, Matthew E. Hurles, Chris Tyler-Smith, Cornelis A. Albers, Qasim Ayub, Senduran Balasubramaniam, Yuan Chen, Vincenza Colonna, Petr Danecek, Luke Jostins, Thomas Keane, Shane McCarthy, Klaudia Walter, Yali Xue, Mark Gerstein, Alexej Abyzov, Suganthi Balasubramanian, Jieming Chen, Declan Clarke, Yao Fu, Arif Harmanci, Mike Jin, Donghoon Lee, Jeremy Liu, Xinmeng Jasmine Mu, Jing Zhang, Yan Zhang, Structural variation group, BGI-Shenzhen, Yingrui Li, Ruibang Luo, Hongmei Zhu, Can Alkan, Elif Dal, Fatma Kahveci, Gabor T. Marth, Erik P. Garrison, Deniz Kural, Wan-Ping Lee, Alistair Ward, Jiantao Wu, Mengyao Zhang, Steven A. McCarroll, Robert E. Handsaker, David M. Altshuler, Eric Banks, Guillermo del Angel, Giulio Genovese, Chris Hartl, Heng Li, Seva Kashin, James Nemesh, Khalid Shakir, Seungtai Yoon, Jayon Lihm, Vladimir Makarov, Jeremiah D. Degenhardt, Jan O. Korbel, Markus H. Fritz, Sascha Meiers, Benjamin Raeder, Tobias Rausch, Adrian M. Stütz, Paul Flicek, Francesco Paolo Casale, Laura Clarke, Richard E. Smith, Oliver Stegle, Xiangqun Zheng-Bradley, Illumina, David R. Bentley, Bret Barnes, R. Keira Cheetham, Michael Eberle, Sean Humphray, Scott D. Kahn, Lisa Murray, Richard J. Shaw, Eric-Wubbo Lameijer, Mark A. Batzer, Miriam K. Konkel, Jerilyn A. Walker, Li Ding, Ira M. Hall, Kai Ye, Phil Lacroute, Charles Lee, Eliza Cerveira, Ankit Malhotra, Jaeho Hwang, Dariusz Plewczyński, Kamen Radew, Mallory Romanovitch, Chengsheng Zhang, David W. Craig, Nils Homer, Deanna M. Church, Chunlin Xiao, Jonathan Sebat, Danny Antaki, Vineet Bafna, Jacob J. Michaelson, Kenny Ye, Scott E. Devine, Eugene J. Gardner, Gonçalo R. Abecasis, Jeffrey M. Kidd, Ryan E. Mills, Gargi Dayama, Sarah Emery, Goo Jun, Xinghua Shi, Andrew Quitadamo, Gerton Lunter, Gil A. McVean, Ken Chen, Xian Fan, Zechen Chong, Tenghui Chen, David J. Witherspoon, Jinchuan Xing, Evan E. Eichler, Mark Chaisson, Fereydoun Hormozdiari, John Huddleston, Maika Malig, Bradley J. Nelson, Peter H. Sudmant, Nicholas F. Parrish, Ekta Khurana, Matthew E. Hurles, Ben Blackburne, Sarah Lindsay, Zemin Ning, Klaudia Walter, Yujun Zhang, Mark Gerstein, Alexej Abyzov, Jieming Chen, Declan Clarke, Hugo Y. K. Lam, Xinmeng Jasmine Mu, Cristina Sisu, Jing Zhang, Yan Zhang, Exome group, Richard A. Gibbs, Fuli Yu, Matthew N. Bainbridge, Danny Challis, Uday S. Evani, Christie Kovar, James T. Lu, Donna Muzny, Uma Nagaswamy, Jeffrey G. Reid, Aniko Sabo, Jin Yu, BGI-Shenzhen, Xiaosen Guo, Wangshen Li, Yingrui Li, Renhua Wu, Gábor Marth, Erik P. Garrison, Wen Fung Leong, Alistair Ward, Guillermo del Angel, Mark A. DePristo, Stacey Gabriel, Namrata Gupta, Chris Hartl, Ryan Poplin, Andrew G. Clark, Juan L. Rodríguez-Flores, Paul Flicek, Laura Clarke, Richard E. Smith, Xiangqun Zheng-Bradley, Daniel G. MacArthur, Elaine R. Mardis, Robert S. Fulton, Daniel C. Koboldt, Simon Gravel, Carlos D. Bustamante, David W. Craig, Alexis Christoforides, Nils Homer, Tyler Izatt, Stephen T. Sherry, Chunlin Xiao, Emmanouil T. Dermitzakis, Gonçalo R. Abecasis, Hyun Min Kang, Gil McVean, Mark B. Gerstein, Suganthi Balasubramanian, Lukas Habegger, Functional interpretation group, Haiyuan Yu, Paul Flicek, Laura Clarke, Fiona Cunningham, Ian Dunham, Daniel R. Zerbino, Xiangqun Zheng-Bradley, Kasper Lage, Jakob Berg Jespersen, Heiko Horn, Stephen B. Montgomery, Marianne K. DeGorter, Ekta Khurana, Chris Tyler‐Smith, Yuan Chen, Vincenza Colonna, Yali Xue, Mark Gerstein, Suganthi Balasubramanian, Yao Fu, Donghoon Kim, Chromosome Y group, Adam Auton, Anthony Marcketta, Rob DeSalle, Apurva Narechania, Melissa A. Wilson Sayres, Erik P. Garrison, Robert E. Handsaker, Seva Kashin, Steven A. McCarroll, Juan L. Rodríguez-Flores, Paul Flicek, Laura Clarke, Xiangqun Zheng-Bradley, Yaniv Erlich, Melissa Gymrek, Thomas Frederick Willems, Carlos D. Bustamante, Fernando L. Méndez, G. David Poznik, Peter A. Underhill, Charles Lee, Eliza Cerveira, Ankit Malhotra, Mallory Romanovitch, Chengsheng Zhang, Gonçalo R. Abecasis, Lachlan Coin, Haojing Shao, David Mittelman, Chris Tyler-Smith, Qasim Ayub, Ruby Banerjee, María Cerezo, Yuan Chen, Thomas W. Fitzgerald, Sandra Louzada, Andrea Massaia, Shane McCarthy, Graham R. S. Ritchie, Yali Xue, Fengtang Yang, Richard A. Gibbs, Christie Kovar, Divya Kalra, Walker Hale, Donna Muzny, Jeffrey G. Reid, BGI-Shenzhen, Jun Wang, Xu Dan, Xiaosen Guo, Guoqing Li, Yingrui Li, Chen Ye, Xiaole Zheng, David M. Altshuler, Paul Flicek, Laura Clarke, Xiangqun Zheng-Bradley, Illumina, David Bentley, Anthony J. Cox, Sean Humphray, Scott Kahn, Ralf Sudbrak, Marcus W. Albrecht, Matthias Lienhard, David E. Larson, David W. Craig, Tyler Izatt, Ahmet Kurdoglu, Stephen T. Sherry, Chunlin Xiao, David Haussler, Gonçalo R. Abecasis, Gil A. McVean, Richard M. Durbin, Senduran Balasubramaniam, Thomas Keane, Shane McCarthy, James Stalker, Samples and ELSI group, Aravinda Chakravarti, Bartha M. Knoppers, Gonçalo R. Abecasis, Kathleen C. Barnes, Christine Beiswanger, Esteban G. Burchard, Carlos D. Bustamante, Hongyu Cai, Hongzhi Cao, Richard M. Durbin, Norman P. Gerry, Neda Gharani, Richard A. Gibbs, Christopher R. Gignoux, Simon Gravel, Brenna M. Henn, D. A. Jones, Lynn B. Jorde, Jane Kaye, Alon Keinan, Alastair Kent, Angeliki Kerasidou, Yingrui Li, Rasika A. Mathias, Gil A. McVean, Andres Moreno-Estrada, Pilar N. Ossorio, Michael Parker, Alissa Resch, Charles N. Rotimi, Charmaine Royal, Karla Sandoval, Yeyang Su, Ralf Sudbrak, Zhongming Tian, Sarah A. Tishkoff, Lorraine H. Toji, Chris Tyler-Smith, Marc Vía, Yuhong Wang, Huanming Yang, Ling Yang, Jiayong Zhu, Sample collection, British from England and Scotland (GBR), Walter F. Bodmer, Colombians in Medellín, Colombia (CLM), Gabriel Bedoya, Andrés Ruiz‐Linares, Han Chinese South (CHS), Zhiming Cai, Yang Gao, Jiayou Chu, Finnish in Finland (FIN), Leena Peltonen, Iberian Populations in Spain (IBS), Andrés C. García‐Montero, Alberto Órfão, Puerto Ricans in Puerto Rico (PUR), Julie Dutil, Juan Carlos Martínez‐Cruzado, Tarás K. Oleksyk, African Caribbean in Barbados (ACB), Kathleen C. Barnes, Rasika A. Mathias, Anselm Hennis, Harold Watson, Colin A. McKenzie, Bengali in Bangladesh (BEB), Firdausi Qadri, Regina C. LaRocque, Pardis C. Sabeti, Chinese Dai in Xishuangbanna, China (CDX), Jiayong Zhu, Xiaoyan Deng, Esan in Nigeria (ESN), Pardis C. Sabeti, Danny Asogun, Onikepe Folarin, Christian Happi, Omonwunmi Omoniwa, Matt Stremlau, Ridhi Tariyal, Gambian in Western Division – Mandinka (GWD), Muminatou Jallow, Fatoumatta Sisay Joof, Tumani Corrah, Kirk A. Rockett, Dominic Kwiatkowski, Indian Telugu in the UK (ITU) and Sri Lankan Tamil in the UK (STU), Jaspal S. Kooner, Kinh in Ho Chi Minh City, Vietnam (KHV), Trâ`n Tịnh Hiê`n, Sarah J. Dunstan, Nguyen Thuy Hang, Mende in Sierra Leone (MSL), Richard Fonnie, Robert F. Garry, Lansana Kanneh, Lina Moses, Pardis C. Sabeti, John S. Schieffelin, Donald S. Grant, Peruvian in Lima, Peru (PEL), Carla Gallo, Giovanni Poletti, Punjabi in Lahore, Pakistan (PJL), Danish Saleheen, Asif Rasheed, Scientific management, Lisa Brooks, Adam L. Felsenfeld, Jean E. McEwen, Yekaterina Vaydylevich, Eric D. Green, Audrey Duncanson, Michael Dunn, Jeffery A. Schloss, Jun Wang, Huanming Yang, Writing group, Adam Auton, Lisa Brooks, Richard Durbin, Erik P. Garrison, Hyun Min Kang, Jan O. Korbel, Jonathan L. Marchini, Shane McCarthy, Gil A. McVean, Gonçalo R. Abecasis - Nature 2015 cited by 20,303

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics. The 1000 Genomes Project has sought to comprehensively catalogue human genetic variation across populations, providing a valuable public genomic resource. The data obtained so far have found applications ranging from association studies and fine mapping studies to the filtering of likely neutral variants in rare-disease cohorts. The authors now report on the final phase of the project, phase 3, which covers previously uncharacterized areas of human genetic diversity in terms of the populations sampled and categories of characterized variation. The sample now includes more than 2,500 individuals from 26 global populations, with low coverage whole-genome and deep exome sequencing, as well as dense microarray genotyping. They find that while most common variants are shared across populations, rarer variants are often restricted to closely related populations. The authors also demonstrate the use of the phase 3 dataset as a reference panel for imputation to improve the resolution in genetic association studies.