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 language | English |
|---|---|
| Pages (from-to) | 56-65 |
| Number of pages | 10 |
| Journal | Nature |
| Volume | 491 |
| Issue number | 7422 |
| DOIs | |
| State | Published - Nov 1 2012 |
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
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Nature, Vol. 491, No. 7422, 01.11.2012, p. 56-65.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - An integrated map of genetic variation from 1,092 human genomes
AU - Altshuler, David M.
AU - Durbin, Richard M.
AU - Abecasis, Gonçalo R.
AU - Bentley, David R.
AU - Chakravarti, Aravinda
AU - Clark, Andrew G.
AU - Donnelly, Peter
AU - Eichler, Evan E.
AU - Flicek, Paul
AU - Gabriel, Stacey B.
AU - Gibbs, Richard A.
AU - Green, Eric D.
AU - Hurles, Matthew E.
AU - Knoppers, Bartha M.
AU - Korbel, Jan O.
AU - Lander, Eric S.
AU - Lee, Charles
AU - Lehrach, Hans
AU - Mardis, Elaine R.
AU - Marth, Gabor T.
AU - McVean, Gil A.
AU - Nickerson, Deborah A.
AU - Schmidt, Jeanette P.
AU - Sherry, Stephen T.
AU - Wang, Jun
AU - Wilson, Richard K.
AU - Dinh, Huyen
AU - Kovar, Christie
AU - Lee, Sandra
AU - Lewis, Lora
AU - Muzny, Donna
AU - Reid, Jeff
AU - Wang, Min
AU - Fang, Xiaodong
AU - Guo, Xiaosen
AU - Jian, Min
AU - Jiang, Hui
AU - Jin, Xin
AU - Li, Guoqing
AU - Li, Jingxiang
AU - Li, Yingrui
AU - Li, Zhuo
AU - Liu, Xiao
AU - Lu, Yao
AU - Ma, Xuedi
AU - Su, Zhe
AU - Tai, Shuaishuai
AU - Tang, Meifang
AU - Wang, Bo
AU - Wang, Guangbiao
AU - Wu, Honglong
AU - Wu, Renhua
AU - Yin, Ye
AU - Zhang, Wenwei
AU - Zhao, Jiao
AU - Zhao, Meiru
AU - Zheng, Xiaole
AU - Zhou, Yan
AU - Gupta, Namrata
AU - Clarke, Laura
AU - Leinonen, Rasko
AU - Smith, Richard E.
AU - Zheng-Bradley, Xiangqun
AU - Grocock, Russell
AU - Humphray, Sean
AU - James, Terena
AU - Kingsbury, Zoya
AU - Sudbrak, Ralf
AU - Albrecht, Marcus W.
AU - Amstislavskiy, Vyacheslav S.
AU - Borodina, Tatiana A.
AU - Lienhard, Matthias
AU - Mertes, Florian
AU - Sultan, Marc
AU - Timmermann, Bernd
AU - Yaspo, Marie Laure
AU - Fulton, Lucinda
AU - Fulton, Robert
AU - Weinstock, George M.
AU - Balasubramaniam, Senduran
AU - Burton, John
AU - Danecek, Petr
AU - Keane, Thomas M.
AU - Kolb-Kokocinski, Anja
AU - McCarthy, Shane
AU - Stalker, James
AU - Quail, Michael
AU - Davies, Christopher J.
AU - Gollub, Jeremy
AU - Webster, Teresa
AU - Wong, Brant
AU - Zhan, Yiping
AU - Auton, Adam
AU - Yu, Fuli
AU - Bainbridge, Matthew
AU - Challis, Danny
AU - Evani, Uday S.
AU - Lu, James
AU - Nagaswamy, Uma
AU - Sabo, Aniko
AU - Wang, Yi
AU - Yu, Jin
AU - Coin, Lachlan J.M.
AU - Fang, Lin
AU - Li, Qibin
AU - Li, Zhenyu
AU - Lin, Haoxiang
AU - Liu, Binghang
AU - Luo, Ruibang
AU - Qin, Nan
AU - Shao, Haojing
AU - Wang, Bingqiang
AU - Xie, Yinlong
AU - Ye, Chen
AU - Yu, Chang
AU - Zhang, Fan
AU - Zheng, Hancheng
AU - Zhu, Hongmei
AU - Garrison, Erik P.
AU - Kural, Deniz
AU - Lee, Wan Ping
AU - Fung Leong, Wen
AU - Ward, Alistair N.
AU - Wu, Jiantao
AU - Zhang, Mengyao
AU - Griffin, Lauren
AU - Hsieh, Chih Heng
AU - Mills, Ryan E.
AU - Shi, Xinghua
AU - Von Grotthuss, Marcin
AU - Zhang, Chengsheng
AU - Daly, Mark J.
AU - Depristo, Mark A.
AU - Banks, Eric
AU - Bhatia, Gaurav
AU - Carneiro, Mauricio O.
AU - Del Angel, Guillermo
AU - Genovese, Giulio
AU - Handsaker, Robert E.
AU - Hartl, Chris
AU - McCarroll, Steven A.
AU - Nemesh, James C.
AU - Poplin, Ryan E.
AU - Schaffner, Stephen F.
AU - Shakir, Khalid
AU - Yoon, Seungtai C.
AU - Lihm, Jayon
AU - Makarov, Vladimir
AU - Jin, Hanjun
AU - Kim, Wook
AU - Cheol Kim, Ki
AU - Rausch, Tobias
AU - Beal, Kathryn
AU - Cunningham, Fiona
AU - Herrero, Javier
AU - McLaren, William M.
AU - Ritchie, Graham R.S.
AU - Gottipati, Srikanth
AU - Keinan, Alon
AU - Rodriguez-Flores, Juan L.
AU - Sabeti, Pardis C.
AU - Grossman, Sharon R.
AU - Tabrizi, Shervin
AU - Tariyal, Ridhi
AU - Cooper, David N.
AU - Ball, Edward V.
AU - Stenson, Peter D.
AU - Barnes, Bret
AU - Bauer, Markus
AU - Keira Cheetham, R.
AU - Cox, Tony
AU - Eberle, Michael
AU - Kahn, Scott
AU - Murray, Lisa
AU - Peden, John
AU - Shaw, Richard
AU - Ye, Kai
AU - Batzer, Mark A.
AU - Konkel, Miriam K.
AU - Walker, Jerilyn A.
AU - MacArthur, Daniel G.
AU - Lek, Monkol
AU - Herwig, Ralf
AU - Shriver, Mark D.
AU - Bustamante, Carlos D.
AU - Byrnes, Jake K.
AU - De La Vega, Francisco M.
AU - Gravel, Simon
AU - Kenny, Eimear E.
AU - Kidd, Jeffrey M.
AU - Maples, Brian K.
AU - Moreno-Estrada, Andres
AU - Zakharia, Fouad
AU - Halperin, Eran
AU - Baran, Yael
AU - Craig, David W.
AU - Christoforides, Alexis
AU - Homer, Nils
AU - Izatt, Tyler
AU - Kurdoglu, Ahmet A.
AU - Sinari, Shripad A.
AU - Squire, Kevin
AU - Xiao, Chunlin
AU - Sebat, Jonathan
AU - Bafna, Vineet
AU - Ye, Kenny
AU - Burchard, Esteban G.
AU - Hernandez, Ryan D.
AU - Gignoux, Christopher R.
AU - Haussler, David
AU - Katzman, Sol J.
AU - James Kent, W.
AU - Howie, Bryan
AU - Ruiz-Linares, Andres
AU - Dermitzakis, Emmanouil T.
AU - Lappalainen, Tuuli
AU - Devine, Scott E.
AU - Liu, Xinyue
AU - Maroo, Ankit
AU - Tallon, Luke J.
AU - Rosenfeld, Jeffrey A.
AU - Michelson, Leslie P.
AU - Min Kang, Hyun
AU - Anderson, Paul
AU - Angius, Andrea
AU - Bigham, Abigail
AU - Blackwell, Tom
AU - Busonero, Fabio
AU - Cucca, Francesco
AU - Fuchsberger, Christian
AU - Jones, Chris
AU - Jun, Goo
AU - Li, Yun
AU - Lyons, Robert
AU - Maschio, Andrea
AU - Porcu, Eleonora
AU - Reinier, Fred
AU - Sanna, Serena
AU - Schlessinger, David
AU - Sidore, Carlo
AU - Tan, Adrian
AU - Kate Trost, Mary
AU - Awadalla, Philip
AU - Hodgkinson, Alan
AU - Lunter, Gerton
AU - Marchini, Jonathan L.
AU - Myers, Simon
AU - Churchhouse, Claire
AU - Delaneau, Olivier
AU - Gupta-Hinch, Anjali
AU - Iqbal, Zamin
AU - Mathieson, Iain
AU - Rimmer, Andy
AU - Xifara, Dionysia K.
AU - Oleksyk, Taras K.
AU - Fu, Yunxin
AU - Liu, Xiaoming
AU - Xiong, Momiao
AU - Jorde, Lynn
AU - Witherspoon, David
AU - Xing, Jinchuan
AU - Browning, Brian L.
AU - Alkan, Can
AU - Hajirasouliha, Iman
AU - Hormozdiari, Fereydoun
AU - Ko, Arthur
AU - Sudmant, Peter H.
AU - Chen, Ken
AU - Chinwalla, Asif
AU - Ding, Li
AU - Dooling, David
AU - Koboldt, Daniel C.
AU - McLellan, Michael D.
AU - Wallis, John W.
AU - Wendl, Michael C.
AU - Zhang, Qunyuan
AU - Tyler-Smith, Chris
AU - Albers, Cornelis A.
AU - Ayub, Qasim
AU - Chen, Yuan
AU - Coffey, Alison J.
AU - Colonna, Vincenza
AU - Huang, Ni
AU - Jostins, Luke
AU - Li, Heng
AU - Scally, Aylwyn
AU - Walter, Klaudia
AU - Xue, Yali
AU - Zhang, Yujun
AU - Gerstein, Mark B.
AU - Abyzov, Alexej
AU - Balasubramanian, Suganthi
AU - Chen, Jieming
AU - Clarke, Declan
AU - Fu, Yao
AU - Habegger, Lukas
AU - Harmanci, Arif O.
AU - Jin, Mike
AU - Khurana, Ekta
AU - Jasmine Mu, Xinmeng
AU - Sisu, Cristina
AU - Degenhardt, Jeremiah
AU - Stütz, Adrian M.
AU - Keira Cheetham, R.
AU - Church, Deanna
AU - Michaelson, Jacob J.
AU - Blackburne, Ben
AU - Lindsay, Sarah J.
AU - Ning, Zemin
AU - Frankish, Adam
AU - Harrow, Jennifer
AU - Mu, Xinmeng Jasmine
AU - Fowler, Gerald
AU - Hale, Walker
AU - Kalra, Divya
AU - Barker, Jonathan
AU - Kelman, Gavin
AU - Kulesha, Eugene
AU - Radhakrishnan, Rajesh
AU - Roa, Asier
AU - Smirnov, Dmitriy
AU - Streeter, Ian
AU - Toneva, Iliana
AU - Vaughan, Brendan
AU - Ananiev, Victor
AU - Belaia, Zinaida
AU - Beloslyudtsev, Dimitriy
AU - Bouk, Nathan
AU - Chen, Chao
AU - Cohen, Robert
AU - Cook, Charles
AU - Garner, John
AU - Hefferon, Timothy
AU - Kimelman, Mikhail
AU - Liu, Chunlei
AU - Lopez, John
AU - Meric, Peter
AU - O'Sullivan, Chris
AU - Ostapchuk, Yuri
AU - Phan, Lon
AU - Ponomarov, Sergiy
AU - Schneider, Valerie
AU - Shekhtman, Eugene
AU - Sirotkin, Karl
AU - Slotta, Douglas
AU - Zhang, Hua
AU - Barnes, Kathleen C.
AU - Beiswanger, Christine
AU - Cai, Hongyu
AU - Cao, Hongzhi
AU - Gharani, Neda
AU - Henn, Brenna
AU - Jones, Danielle
AU - Kaye, Jane S.
AU - Kent, Alastair
AU - Kerasidou, Angeliki
AU - Mathias, Rasika
AU - Ossorio, Pilar N.
AU - Parker, Michael
AU - Reich, David
AU - Rotimi, Charles N.
AU - Royal, Charmaine D.
AU - Sandoval, Karla
AU - Su, Yeyang
AU - Tian, Zhongming
AU - Tishkoff, Sarah
AU - Toji, Lorraine H.
AU - Via, Marc
AU - Wang, Yuhong
AU - Yang, Huanming
AU - Yang, Ling
AU - Zhu, Jiayong
AU - Bodmer, Walter
AU - Bedoya, Gabriel
AU - Ming, Cai Zhi
AU - Yang, Gao
AU - Jia You, Chu
AU - Peltonen, Leena
AU - Garcia-Montero, Andres
AU - Orfao, Alberto
AU - Dutil, Julie
AU - Martinez-Cruzado, Juan C.
AU - Brooks, Lisa D.
AU - Felsenfeld, Adam L.
AU - McEwen, Jean E.
AU - Clemm, Nicholas C.
AU - Duncanson, Audrey
AU - Dunn, Michael
AU - Guyer, Mark S.
AU - Peterson, Jane L.
AU - Lacroute, Phil
N1 - Funding Information: Acknowledgements We thank many people who contributed to this project: A. Naranjo, M. V. Parra and C. Duque for help with the collection of the Colombian samples; N. Kälin and F. Laplace for discussions; A. Schlattl and T. Zichner for assistance in managing data sets; E. Appelbaum, H. Arbery, E. Birney, S. Bumpstead, J. Camarata, J. Carey, G. Cochrane, M. DaSilva, S. Dökel, E. Drury, C. Duque, K. Gyaltsen, P. Jokinen, B. Lenz, S. Lewis, D. Lu, A. Naranjo, S. Ott, I. Padioleau, M. V. Parra, N. Patterson, A. Price, L. Sadzewicz, S. Schrinner, N. Sengamalay, J. Sullivan, F. Ta, Y. Vaydylevich, O. Venn, K. Watkins and A. Yurovsky for assistance, discussion and advice. We thank the people who generously contributed their samples, from these populations: Yoruba in Ibadan, Nigeria; the Han Chinese in Beijing, China; the Japanese in Tokyo, Japan; the Utah CEPH community; the Luhya in Webuye, Kenya; people with African ancestry in the Southwest United States; the Toscani in Italia; people with Mexican ancestry in Los Angeles, California; the Southern Han Chinese in China; the British in England and Scotland; the Finnish in Finland; the Iberian Populations in Spain; the Colombians in Medellin, Colombia; and the Puerto Ricans in Puerto Rico. This research was supported in part by Wellcome Trust grants WT098051 to R.M.D., M.E.H. and C.T.S.; WT090532/Z/09/Z, WT085475/Z/08/Z and WT095552/ Z/11/ZtoP.Do.; WT086084/Z/08/ZandWT090532/Z/09/Z to G.A.M.;WT089250/Z/ 09/Z to I.M.; WT085532AIA to P.F.; Medical Research Council grant G0900747(91070) to G.A.M.; British Heart Foundation grant RG/09/12/28096 to C.A.A.; the National Basic Research Program of China (973 program no. 2011CB809201, 2011CB809202 and 2011CB809203); the Chinese 863 program (2012AA02A201); the National Natural Science Foundation of China (30890032, 31161130357); the Shenzhen Key Laboratory of Transomics Biotechnologies (CXB201108250096A); the Shenzhen Municipal Government of China (grants ZYC200903240080A and ZYC201105170397A); Guangdong Innovative Research Team Program (no. 2009010016); BMBF grant 01GS08201 to H.Le.; BMBF grant 0315428A to R.H.; the Max Planck Society; Swiss National Science Foundation 31003A_130342 to E.T.D.; Swiss National Science Foundation NCCR ‘Frontiers in Genetics’ grant to E.T.D.; Louis Jeantet Foundation grant to E.T.D.; Biotechnology and BiologicalSciences ResearchCouncil(BBSRC)grantBB/I021213/1 toA.R.-L.;German Research Foundation (Emmy Noether Fellowship KO 4037/1-1) to J.O.K.; Netherlands Organization for Scientific Research VENI grant 639.021.125 to K.Y.; Beatriu de Pinos Program grants 2006BP-A 10144 and 2009BP-B 00274 to M.V.; Israeli Science Foundation grant 04514831 to E.H.; Genome Québec and the Ministry of Economic Development,InnovationandTrade grantPSR-SIIRI-195toP.Aw.;NationalInstitutes of Health (NIH) grants UO1HG5214, RC2HG5581 and RO1MH84698 to G.R.A.; R01HG4719 and R01HG3698 to G.T.M; RC2HG5552 and UO1HG6513 to G.R.A. and G.T.M.; R01HG4960 and R01HG5701 to B.L.B.; U01HG5715 to C.D.B. and A.G.C.; T32GM8283 to D.Cl.; U01HG5208 to M.J.D.; U01HG6569 to M.A.D.; R01HG2898 and R01CA166661 to S.E.D.; UO1HG5209, UO1HG5725 and P41HG4221 to C.Le.; P01HG4120 to E.E.E.; U01HG5728 to Yu.F.; U54HG3273 and U01HG5211 to R.A.G.; R01HL95045 to S.B.G.; U41HG4568 to S.J.K.; P41HG2371 to W.J.K.; ES015794, AI077439, HL088133 and HL078885 to E.G.B.; RC2HL102925 to S.B.G. and D.M.A.; R01GM59290 to L.B.J. and M.A.B.; U54HG3067 to E.S.L. and S.B.G.; T15LM7033 to B.K.M.; T32HL94284 to J.L.R.-F.; DP2OD6514 and BAA-NIAID-DAIT-NIHAI2009061 to P.C.S.; T32GM7748 to X.S.; U54HG3079 to R.K.W.; UL1RR024131 to R.D.H.; HHSN268201100040C to the Coriell Institute for Medical Research; a Sandler Foundation award and an American Asthma Foundation award to E.G.B.; an IBM Open CollaborativeResearchProgramaward toY.B.;anA.G. LeventisFoundationscholarship to D.K.X.; a Wolfson Royal Society Merit Award to P.Do.; a Howard Hughes Medical Institute International Fellowship award to P.H.S.; a grant from T. and V. Stanley to S.C.Y.;and aMaryBerylPatchTurnbullScholarProgramaward toK.C.B.E.H.isafaculty fellow of the Edmond J. Safra Bioinformatics program at Tel-Aviv University. E.E.E. and D.H. are investigators of the Howard Hughes Medical Institute. M.V.G. is a long-term fellow of EMBO.
PY - 2012/11/1
Y1 - 2012/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84975795680&partnerID=8YFLogxK
U2 - 10.1038/nature11632
DO - 10.1038/nature11632
M3 - Article
C2 - 23128226
AN - SCOPUS:84975795680
SN - 0028-0836
VL - 491
SP - 56
EP - 65
JO - Nature
JF - Nature
IS - 7422
ER -