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An integrated map of genetic variation from 1,092 human genomes
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 An integrated map of genetic variation from 1,092 human genomes.pdf | Published version | 1.49 MB | Adobe PDF | View/Open |
| Title: | An integrated map of genetic variation from 1,092 human genomes |
| Authors: | Altshuler, DM Durbin, RM Abecasis, GR Bentley, DR Chakravarti, A Clark, AG Donnelly, P Eichler, EE Flicek, P Gabriel, SB Gibbs, RA Green, ED Hurles, ME Knoppers, BM Korbel, JO Lander, ES Lee, C Lehrach, H Mardis, ER Marth, GT McVean, GA Nickerson, DA Schmidt, JP Sherry, ST Wang, J Wilson, RK Gibbs, RA Dinh, H Kovar, C Lee, S Lewis, L Muzny, D Reid, J Wang, M Wang, J Fang, X Guo, X Jian, M Jiang, H Jin, X Li, G Li, J Li, Y Li, Z Liu, X Lu, Y Ma, X Su, Z Tai, S Tang, M Wang, B Wang, G Wu, H Wu, R Yin, Y Zhang, W Zhao, J Zhao, M Zheng, X Zhou, Y Lander, ES Altshuler, DM Gabriel, SB Gupta, N Flicek, P Clarke, L Leinonen, R Smith, RE Zheng-Bradley, X Bentley, DR Grocock, R Humphray, S James, T Kingsbury, Z Lehrach, H Sudbrak, R Albrecht, MW Amstislavskiy, VS Borodina, TA Lienhard, M Mertes, F Sultan, M Timmermann, B Yaspo, M-L Sherry, ST McVean, GA Mardis, ER Wilson, RK Fulton, L Fulton, R Weinstock, GM Durbin, RM Balasubramaniam, S Burton, J Danecek, P Keane, TM Kolb-Kokocinski, A McCarthy, S Stalker, J Quail, M Schmidt, JP Davies, CJ Gollub, J Webster, T Wong, B Zhan, Y Auton, A Gibbs, RA Yu, F Bainbridge, M Challis, D Evani, US Lu, J Muzny, D Nagaswamy, U Reid, J Sabo, A Wang, Y Yu, J Wang, J Coin, LJM Fang, L Guo, X Jin, X Li, G Li, Q Li, Y Li, Z Lin, H Liu, B Luo, R Qin, N Shao, H Wang, B Xie, Y Ye, C Yu, C Zhang, F Zheng, H Zhu, H Marth, GT Garrison, EP Kural, D Lee, W-P Leong, WF Ward, AN Wu, J Zhang, M Lee, C Griffin, L Hsieh, C-H Mills, RE Shi, X Von Grotthuss, M Zhang, C Daly, MJ DePristo, MA Altshuler, DM Banks, E Bhatia, G Carneiro, MO Del Angel, G Gabriel, SB Genovese, G Gupta, N Handsaker, RE Hartl, C Lander, ES McCarroll, SA Nemesh, JC Poplin, RE Schaffner, SF Shakir, K Yoon, SC Lihm, J Makarov, V Jin, H Kim, W Kim, KC Korbel, JO Rausch, T Flicek, P Beal, K Clarke, L Cunningham, F Herrero, J McLaren, WM Ritchie, GRS Smith, RE Zheng-Bradley, X Clark, AG Gottipati, S Keinan, A Rodriguez-Flores, JL Sabeti, PC Grossman, SR Tabrizi, S Tariyal, R Cooper, DN Ball, EV Stenson, PD Bentley, DR Barnes, B Bauer, M Cheetham, RK Cox, T Eberle, M Humphray, S Kahn, S Murray, L Peden, J Shaw, R Ye, K Batzer, MA Konkel, MK Walker, JA MacArthur, DG Lek, M Sudbrak, R Amstislavskiy, VS Herwig, R Shriver, MD Bustamante, CD Byrnes, JK De la Vega, FM Gravel, S Kenny, EE Kidd, JM Lacroute, P Maples, BK Moreno-Estrada, A Zakharia, F Halperin, E Baran, Y Craig, DW Christoforides, A Homer, N Izatt, T Kurdoglu, AA Sinari, SA Squire, K Sherry, ST Xiao, C Sebat, J Bafna, V Ye, K Burchard, EG Hernandez, RD Gignoux, CR Haussler, D Katzman, SJ Kent, WJ Howie, B Ruiz-Linares, A Dermitzakis, ET Lappalainen, T Devine, SE Liu, X Maroo, A Tallon, LJ Rosenfeld, JA Michelson, LP Abecasis, GR Kang, HM Anderson, P Angius, A Bigham, A Blackwell, T Busonero, F Cucca, F Fuchsberger, C Jones, C Jun, G Li, Y Lyons, R Maschio, A Porcu, E Reinier, F Sanna, S Schlessinger, D Sidore, C Tan, A Trost, MK Awadalla, P Hodgkinson, A Lunter, G McVean, GA Marchini, JL Myers, S Churchhouse, C Delaneau, O Gupta-Hinch, A Iqbal, Z Mathieson, I Rimmer, A Xifara, DK Oleksyk, TK Fu, Y Liu, X Xiong, M Jorde, L Witherspoon, D Xing, J Eichler, EE Browning, BL Alkan, C Hajirasouliha, I Hormozdiari, F Ko, A Sudmant, PH Mardis, ER Chen, K Chinwalla, A Ding, L Dooling, D Koboldt, DC McLellan, MD Wallis, JW Wendl, MC Zhang, Q Durbin, RM Hurles, ME Tyler-Smith, C Albers, CA Ayub, Q Balasubramaniam, S Chen, Y Coffey, AJ Colonna, V Danecek, P Huang, N Jostins, L Keane, TM Li, H McCarthy, S Scally, A Stalker, J Walter, K Xue, Y Zhang, Y Gerstein, MB Abyzov, A Balasubramanian, S Chen, J Clarke, D Fu, Y Habegger, L Harmanci, AO Jin, M Khurana, E Mu, XJ Sisu, C Li, Y Luo, R Zhu, H Lee, C Griffin, L Hsieh, C-H Mills, RE Shi, X Von Grotthuss, M Zhang, C Marth, GT Garrison, EP Kural, D Lee, W-P Ward, AN Wu, J Zhang, M McCarroll, SA Altshuler, DM Banks, E Del Angel, G Genovese, G Handsaker, RE Hartl, C Nemesh, JC Shakir, K Yoon, SC Lihm, J Makarov, V Degenhardt, J Flicek, P Clarke, L Smith, RE Zheng-Bradley, X Korbel, JO Rausch, T Stuetz, AM Bentley, DR Barnes, B Cheetham, RK Eberle, M Humphray, S Kahn, S Murray, L Shaw, R Ye, K Batzer, MA Konkel, MK Walker, JA Lacroute, P Craig, DW Homer, N Church, D Xiao, C Sebat, J Bafna, V Michaelson, JJ Ye, K Devine, SE Liu, X Maroo, A Tallon, LJ Lunter, G McVean, GA Iqbal, Z Witherspoon, D Xing, J Eichler, EE Alkan, C Hajirasouliha, I Hormozdiari, F Ko, A Sudmant, PH Chen, K Chinwalla, A Ding, L McLellan, MD Wallis, JW Hurles, ME Ben, B Li, H Lindsay, SJ Ning, Z Scally, A Walter, K Zhang, Y Gerstein, MB Abyzov, A Chen, J Clarke, D Khurana, E Mu, XJ Sisu, C Gibbs, RA Yu, F Bainbridge, M Challis, D Evani, US Kovar, C Lewis, L Lu, J Muzny, D Nagaswamy, U Reid, J Sabo, A Yu, J Guo, X Li, Y Wu, R Marth, GT Garrison, EP Leong, WF Ward, AN Del Angel, G DePristo, MA Gabriel, SB Gupta, N Hartl, C Poplin, RE Clark, AG Rodriguez-Flores, JL Flicek, P Clarke, L Smith, RE Zheng-Bradley, X MacArthur, DG Bustamante, CD Gravel, S Craig, DW Christoforides, A Homer, N Izatt, T Sherry, ST Xiao, C Dermitzakis, ET Abecasis, GR Kang, HM McVean, GA Mardis, ER Dooling, D Fulton, L Fulton, R Koboldt, DC Durbin, RM Balasubramaniam, S Keane, TM McCarthy, S Stalker, J Gerstein, MB Balasubramanian, S Habegger, L Garrison, EP Gibbs, RA Bainbridge, M Muzny, D Yu, F Yu, J Del Angel, G Handsaker, RE Makarov, V Rodriguez-Flores, JL Jin, H Kim, W Kim, KC Flicek, P Beal, K Clarke, L Cunningham, F Herrero, J McLaren, WM Ritchie, GRS Zheng-Bradley, X Tabrizi, S MacArthur, DG Lek, M Bustamante, CD De la Vega, FM Craig, DW Kurdoglu, AA Lappalainen, T Rosenfeld, JA Michelson, LP Awadalla, P Hodgkinson, A McVean, GA Chen, K Tyler-Smith, C Chen, Y Colonna, V Frankish, A Harrow, J Xue, Y Gerstein, MB Abyzov, A Balasubramanian, S Chen, J Clarke, D Fu, Y Harmanci, AO Jin, M Khurana, E Mu, XJ Sisu, C Gibbs, RA Fowler, G Hale, W Kalra, D Kovar, C Muzny, D Reid, J Wang, J Guo, X Li, G Li, Y Zheng, X Altshuler, DM Flicek, P Clarke, L Barker, J Kelman, G Kulesha, E Leinonen, R McLaren, WM Radhakrishnan, R Roa, A Smirnov, D Smith, RE Streeter, I Toneva, I Vaughan, B Zheng-Bradley, X Bentley, DR Cox, T Humphray, S Kahn, S Sudbrak, R Albrecht, MW Lienhard, M Craig, DW Izatt, T Kurdoglu, AA Sherry, ST Ananiev, V Belaia, Z Beloslyudtsev, D Bouk, N Chen, C Church, D Cohen, R Cook, C Garner, J Hefferon, T Kimelman, M Liu, C Lopez, J Meric, P O'Sullivan, C Ostapchuk, Y Phan, L Ponomarov, S Schneider, V Shekhtman, E Sirotkin, K Slotta, D Xiao, C Zhang, H Haussler, D Abecasis, GR McVean, GA Alkan, C Ko, A Dooling, D Durbin, RM Balasubramaniam, S Keane, TM McCarthy, S Stalker, J Chakravarti, A Knoppers, BM Abecasis, GR Barnes, KC Beiswanger, C Burchard, EG Bustamante, CD Cai, H Cao, H Durbin, RM Gharani, N Gibbs, RA Gignoux, CR Gravel, S Henn, B Jones, D Jorde, L Kaye, JS Keinan, A Kent, A Kerasidou, A Li, Y Mathias, R McVean, GA Moreno-Estrada, A Ossorio, PN Parker, M Reich, D Rotimi, CN Royal, CD Sandoval, K Su, Y Sudbrak, R Tian, Z Timmermann, B Tishkoff, S Toji, LH Tyler-Smith, C Via, M Wang, Y Yang, H Yang, L Zhu, J Bodmer, W Bedoya, G Ruiz-Linares, A Ming, CZ Yang, G You, CJ Peltonen, L Garcia-Montero, A Orfao, A Dutil, J Martinez-Cruzado, JC Oleksyk, TK Brooks, LD Felsenfeld, AL McEwen, JE Clemm, NC Duncanson, A Dunn, M Green, ED Guyer, MS Peterson, JL Abecasis, GR Auton, A Brooks, LD DePristo, MA Durbin, RM Handsaker, RE Kang, HM Marth, GT McVean, GA |
| Item Type: | Journal Article |
| 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. |
| Issue Date: | 1-Nov-2012 |
| Date of Acceptance: | 1-Oct-2012 |
| URI: | http://hdl.handle.net/10044/1/96192 |
| DOI: | 10.1038/nature11632 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Research |
| Start Page: | 56 |
| End Page: | 65 |
| Journal / Book Title: | Nature |
| Volume: | 491 |
| Issue: | 7422 |
| Copyright Statement: | ©2012 Macmillan Publishers Limited. All rights reserved. This article is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence (http://creativecommons.org/licenses/by-nc-sa/3.0/), which permits distribution, and reproduction in any medium, provided the original author and source are credited. This licence does not permit commercial exploitation, and derivative works must be licensed under the same or similar licence. |
| Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics COPY NUMBER VARIATION WIDE ASSOCIATION POPULATION-STRUCTURE RARE VARIANTS LOCI MUTATION RISK Alleles Binding Sites Conserved Sequence Evolution, Molecular Genetic Variation Genetics, Medical Genetics, Population Genome, Human Genome-Wide Association Study Genomics Haplotypes Humans Nucleotide Motifs Polymorphism, Single Nucleotide Racial Groups Sequence Deletion Transcription Factors 1000 Genomes Project Consortium Humans Transcription Factors Genetics, Medical Genetics, Population Genomics Evolution, Molecular Sequence Deletion Binding Sites Conserved Sequence Haplotypes Polymorphism, Single Nucleotide Alleles Genome, Human Genetic Variation Genome-Wide Association Study Nucleotide Motifs Racial Groups Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics COPY NUMBER VARIATION WIDE ASSOCIATION POPULATION-STRUCTURE RARE VARIANTS LOCI MUTATION RISK General Science & Technology |
| Publication Status: | Published |
| Online Publication Date: | 2012-10-31 |
| Appears in Collections: | Department of Infectious Diseases National Heart and Lung Institute |
This item is licensed under a Creative Commons License
