A map of human genome variation from population-scale sequencing View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-10-27

AUTHORS

Richard M. Durbin, David Altshuler, Richard M. Durbin, Gonçalo R. Abecasis, David R. Bentley, Aravinda Chakravarti, Andrew G. Clark, Francis S. Collins, Francisco M. De La Vega, Peter Donnelly, Michael Egholm, Paul Flicek, Stacey B. Gabriel, Richard A. Gibbs, Bartha M. Knoppers, Eric S. Lander, Hans Lehrach, Elaine R. Mardis, Gil A. McVean, Deborah A. Nickerson, Leena Peltonen, Alan J. Schafer, Stephen T. Sherry, Jun Wang, Richard K. Wilson, Richard A. Gibbs, David Deiros, Mike Metzker, Donna Muzny, Jeff Reid, David Wheeler, Jun Wang, Jingxiang Li, Min Jian, Guoqing Li, Ruiqiang Li, Huiqing Liang, Geng Tian, Bo Wang, Jian Wang, Wei Wang, Huanming Yang, Xiuqing Zhang, Huisong Zheng, Eric S. Lander, David Altshuler, Lauren Ambrogio, Toby Bloom, Kristian Cibulskis, Tim J. Fennell, Stacey B. Gabriel, David B. Jaffe, Erica Shefler, Carrie L. Sougnez, David R. Bentley, Niall Gormley, Sean Humphray, Zoya Kingsbury, Paula Kokko-Gonzales, Jennifer Stone, Kevin J. McKernan, Gina L. Costa, Jeffry K. Ichikawa, Clarence C. Lee, Ralf Sudbrak, Hans Lehrach, Tatiana A. Borodina, Andreas Dahl, Alexey N. Davydov, Peter Marquardt, Florian Mertes, Wilfiried Nietfeld, Philip Rosenstiel, Stefan Schreiber, Aleksey V. Soldatov, Bernd Timmermann, Marius Tolzmann, Michael Egholm, Jason Affourtit, Dana Ashworth, Said Attiya, Melissa Bachorski, Eli Buglione, Adam Burke, Amanda Caprio, Christopher Celone, Shauna Clark, David Conners, Brian Desany, Lisa Gu, Lorri Guccione, Kalvin Kao, Andrew Kebbel, Jennifer Knowlton, Matthew Labrecque, Louise McDade, Craig Mealmaker, Melissa Minderman, Anne Nawrocki, Faheem Niazi, Kristen Pareja, Ravi Ramenani, David Riches, Wanmin Song, Cynthia Turcotte, Shally Wang, Elaine R. Mardis, Richard K. Wilson, David Dooling, Lucinda Fulton, Robert Fulton, George Weinstock, Richard M. Durbin, John Burton, David M. Carter, Carol Churcher, Alison Coffey, Anthony Cox, Aarno Palotie, Michael Quail, Tom Skelly, James Stalker, Harold P. Swerdlow, Daniel Turner, Anniek De Witte, Shane Giles, Richard A. Gibbs, David Wheeler, Matthew Bainbridge, Danny Challis, Aniko Sabo, Fuli Yu, Jin Yu, Jun Wang, Xiaodong Fang, Xiaosen Guo, Ruiqiang Li, Yingrui Li, Ruibang Luo, Shuaishuai Tai, Honglong Wu, Hancheng Zheng, Xiaole Zheng, Yan Zhou, Guoqing Li, Jian Wang, Huanming Yang, Gabor T. Marth, Erik P. Garrison, Weichun Huang, Amit Indap, Deniz Kural, Wan-Ping Lee, Wen Fung Leong, Aaron R. Quinlan, Chip Stewart, Michael P. Stromberg, Alistair N. Ward, Jiantao Wu, Charles Lee, Ryan E. Mills, Xinghua Shi, Mark J. Daly, Mark A. DePristo, David Altshuler, Aaron D. Ball, Eric Banks, Toby Bloom, Brian L. Browning, Kristian Cibulskis, Tim J. Fennell, Kiran V. Garimella, Sharon R. Grossman, Robert E. Handsaker, Matt Hanna, Chris Hartl, David B. Jaffe, Andrew M. Kernytsky, Joshua M. Korn, Heng Li, Jared R. Maguire, Steven A. McCarroll, Aaron McKenna, James C. Nemesh, Anthony A. Philippakis, Ryan E. Poplin, Alkes Price, Manuel A. Rivas, Pardis C. Sabeti, Stephen F. Schaffner, Erica Shefler, Ilya A. Shlyakhter, David N. Cooper, Edward V. Ball, Matthew Mort, Andrew D. Phillips, Peter D. Stenson, Jonathan Sebat, Vladimir Makarov, Kenny Ye, Seungtai C. Yoon, Carlos D. Bustamante, Laura Clarke, Paul Flicek, Fiona Cunningham, Javier Herrero, Stephen Keenen, Eugene Kulesha, Rasko Leinonen, William M. McLaren, Rajesh Radhakrishnan, Richard E. Smith, Vadim Zalunin, Xiangqun Zheng-Bradley, Jan O. Korbel, Adrian M. Stütz, Sean Humphray, Markus Bauer, R. Keira Cheetham, Tony Cox, Michael Eberle, Terena James, Scott Kahn, Lisa Murray, Aravinda Chakravarti, Kai Ye, Francisco M. De La Vega, Yutao Fu, Fiona C. L. Hyland, Jonathan M. Manning, Stephen F. McLaughlin, Heather E. Peckham, Onur Sakarya, Yongming A. Sun, Eric F. Tsung, Mark A. Batzer, Miriam K. Konkel, Jerilyn A. Walker, Ralf Sudbrak, Marcus W. Albrecht, Vyacheslav S. Amstislavskiy, Ralf Herwig, Dimitri V. Parkhomchuk, Stephen T. Sherry, Richa Agarwala, Hoda M. Khouri, Aleksandr O. Morgulis, Justin E. Paschall, Lon D. Phan, Kirill E. Rotmistrovsky, Robert D. Sanders, Martin F. Shumway, Chunlin Xiao, Gil A. McVean, Adam Auton, Zamin Iqbal, Gerton Lunter, Jonathan L. Marchini, Loukas Moutsianas, Simon Myers, Afidalina Tumian, Brian Desany, James Knight, Roger Winer, David W. Craig, Steve M. Beckstrom-Sternberg, Alexis Christoforides, Ahmet A. Kurdoglu, John V. Pearson, Shripad A. Sinari, Waibhav D. Tembe, David Haussler, Angie S. Hinrichs, Sol J. Katzman, Andrew Kern, Robert M. Kuhn, Molly Przeworski, Ryan D. Hernandez, Bryan Howie, Joanna L. Kelley, S. Cord Melton, Gonçalo R. Abecasis, Yun Li, Paul Anderson, Tom Blackwell, Wei Chen, William O. Cookson, Jun Ding, Hyun Min Kang, Mark Lathrop, Liming Liang, Miriam F. Moffatt, Paul Scheet, Carlo Sidore, Matthew Snyder, Xiaowei Zhan, Sebastian Zöllner, Philip Awadalla, Reed A. Cartwright, Ferran Casals, Youssef Idaghdour, Jonathan Keebler, Eric A. Stone, Martine Zilversmit, Lynn Jorde, Jinchuan Xing, Evan E. Eichler, Gozde Aksay, Can Alkan, Iman Hajirasouliha, Elaine R. Mardis, Ken Chen, Asif Chinwalla, Li Ding, Daniel C. Koboldt, Mike D. McLellan, David Dooling, George Weinstock, John W. Wallis, Michael C. Wendl, Qunyuan Zhang, Richard M. Durbin, Cornelis A. Albers, Qasim Ayub, Senduran Balasubramaniam, Jeffrey C. Barrett, David M. Carter, Yuan Chen, Donald F. Conrad, Petr Danecek, Emmanouil T. Dermitzakis, Min Hu, Ni Huang, Matt E. Hurles, Hanjun Jin, Luke Jostins, Thomas M. Keane, Si Quang Le, Sarah Lindsay, Quan Long, Daniel G. MacArthur, Stephen B. Montgomery, Leopold Parts, James Stalker, Chris Tyler-Smith, Klaudia Walter, Yali Xue, Yujun Zhang, Mark B. Gerstein, Michael Snyder, Alexej Abyzov, Suganthi Balasubramanian, Robert Bjornson, Jiang Du, Fabian Grubert, Lukas Habegger, Rajini Haraksingh, Justin Jee, Ekta Khurana, Hugo Y. K. Lam, Jing Leng, Xinmeng Jasmine Mu, Alexander E. Urban, Zhengdong Zhang, Yingrui Li, Ruibang Luo, Gabor T. Marth, Erik P. Garrison, Deniz Kural, Aaron R. Quinlan, Chip Stewart, Michael P. Stromberg, Alistair N. Ward, Jiantao Wu, Charles Lee, Ryan E. Mills, Xinghua Shi, Steven A. McCarroll, Eric Banks, Mark A. DePristo, Robert E. Handsaker, Chris Hartl, Joshua M. Korn, Heng Li, James C. Nemesh, Jonathan Sebat, Vladimir Makarov, Kenny Ye, Seungtai C. Yoon, Jeremiah Degenhardt, Mark Kaganovich, Laura Clarke, Richard E. Smith, Xiangqun Zheng-Bradley, Jan O. Korbel, Sean Humphray, R. Keira Cheetham, Michael Eberle, Scott Kahn, Lisa Murray, Kai Ye, Francisco M. De La Vega, Yutao Fu, Heather E. Peckham, Yongming A. Sun, Mark A. Batzer, Miriam K. Konkel, Jerilyn A. Walker, Chunlin Xiao, Zamin Iqbal, Brian Desany, Tom Blackwell, Matthew Snyder, Jinchuan Xing, Evan E. Eichler, Gozde Aksay, Can Alkan, Iman Hajirasouliha, Fereydoun Hormozdiari, Jeffrey M. Kidd, Ken Chen, Asif Chinwalla, Li Ding, Mike D. McLellan, John W. Wallis, Matt E. Hurles, Donald F. Conrad, Klaudia Walter, Yujun Zhang, Mark B. Gerstein, Michael Snyder, Alexej Abyzov, Jiang Du, Fabian Grubert, Rajini Haraksingh, Justin Jee, Ekta Khurana, Hugo Y. K. Lam, Jing Leng, Xinmeng Jasmine Mu, Alexander E. Urban, Zhengdong Zhang, Richard A. Gibbs, Matthew Bainbridge, Danny Challis, Cristian Coafra, Huyen Dinh, Christie Kovar, Sandy Lee, Donna Muzny, Lynne Nazareth, Jeff Reid, Aniko Sabo, Fuli Yu, Jin Yu, Gabor T. Marth, Erik P. Garrison, Amit Indap, Wen Fung Leong, Aaron R. Quinlan, Chip Stewart, Alistair N. Ward, Jiantao Wu, Kristian Cibulskis, Tim J. Fennell, Stacey B. Gabriel, Kiran V. Garimella, Chris Hartl, Erica Shefler, Carrie L. Sougnez, Jane Wilkinson, Andrew G. Clark, Simon Gravel, Fabian Grubert, Laura Clarke, Paul Flicek, Richard E. Smith, Xiangqun Zheng-Bradley, Stephen T. Sherry, Hoda M. Khouri, Justin E. Paschall, Martin F. Shumway, Chunlin Xiao, Gil A. McVean, Sol J. Katzman, Gonçalo R. Abecasis, Tom Blackwell, Elaine R. Mardis, David Dooling, Lucinda Fulton, Robert Fulton, Daniel C. Koboldt, Richard M. Durbin, Senduran Balasubramaniam, Allison Coffey, Thomas M. Keane, Daniel G. MacArthur, Aarno Palotie, Carol Scott, James Stalker, Chris Tyler-Smith, Mark B. Gerstein, Suganthi Balasubramanian, Aravinda Chakravarti, Bartha M. Knoppers, Leena Peltonen, Gonçalo R. Abecasis, Carlos D. Bustamante, Neda Gharani, Richard A. Gibbs, Lynn Jorde, Jane S. Kaye, Alastair Kent, Taosha Li, Amy L. McGuire, Gil A. McVean, Pilar N. Ossorio, Charles N. Rotimi, Yeyang Su, Lorraine H. Toji, Chris Tyler-Smith, Lisa D. Brooks, Adam L. Felsenfeld, Jean E. McEwen, Assya Abdallah, Christopher R. Juenger, Nicholas C. Clemm, Francis S. Collins, Audrey Duncanson, Eric D. Green, Mark S. Guyer, Jane L. Peterson, Alan J. Schafer, Gonçalo R. Abecasis, David Altshuler, Adam Auton, Lisa D. Brooks, Richard M. Durbin, Richard A. Gibbs, Matt E. Hurles, Gil A. McVean

ABSTRACT

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother–father–child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research. More... »

PAGES

1061-1073

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  • Journal

    TITLE

    Nature

    ISSUE

    7319

    VOLUME

    467

    Author Affiliations

  • Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK
  • Illumina Cambridge Ltd, Chesterford Research Park, Little Chesterford, Nr Saffron Walden, Essex CB10 1XL, UK
  • McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 21205, Baltimore, Maryland, USA
  • Center for Comparative and Population Genomics, Cornell University, 14850, Ithaca, New York, USA
  • US National Institutes of Health, 1 Center Drive, 20892, Bethesda, Maryland, USA
  • Life Technologies, 94404, Foster City, California, USA
  • Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK
  • Pall Corporation, 25 Harbor Park Drive, 11050, Port Washington, New York, USA
  • European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK
  • The Broad Institute of MIT and Harvard, 7 Cambridge Center, 02142, Cambridge, Massachusetts, USA
  • Human Genome Sequencing Center, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, Texas, USA
  • Centre of Genomics and Policy, McGill University, Montréal, Québec H3A 1A4, Canada
  • Max Planck Institute for Molecular Genetics, D-14195 Berlin-Dahlem, Germany
  • The Genome Center, Washington University School of Medicine, 63108, St Louis, Missouri, USA
  • Department of Genome Sciences, University of Washington School of Medicine, 98195, Seattle, Washington, USA
  • Wellcome Trust, Gibbs Building, 215 Euston Road, London NW1 2BE, UK
  • US National Institutes of Health, National Center for Biotechnology Information, 45 Center Drive, 20892, Bethesda, Maryland, USA
  • Department of Biology, University of Copenhagen 2200, Denmark
  • BGI-Shenzhen, 518083, Shenzhen, China
  • Department of Genetics, Harvard Medical School, 02115, Cambridge, Massachusetts, USA
  • Life Technologies, 01915, Beverly, Massachusetts, USA
  • Deep Sequencing Group, Biotechnology Center TU Dresden, Tatzberg 47/49, 01307 Dresden, Germany
  • Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel 24105, Germany
  • Roche Applied Science, 20 Commercial Street, 06405, Branford, Connecticut, USA
  • Department of Medical Genetics, Institute of Molecular Medicine (FIMM) of the University of Helsinki and Helsinki University Hospital, Helsinki 00290, Finland
  • Agilent Technologies Inc., 95051, Santa Clara, California, USA
  • Department of Biology, Boston College, 02467, Chestnut Hill, Massachusetts, USA
  • US National Institutes of Health, National Institute of Environmental Health Sciences, 111 T W Alexander Drive, Research Triangle Park, 27709, North Carolina, USA
  • Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, 22908, Charlottesville, Virginia, USA
  • Illumina, 92121, San Diego, California, USA
  • Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Department of Medicine, Division of Medical Genetics, University of Washington, 98195, Seattle, Washington, USA
  • Department of Organismic and Evolutionary Biology, Center for Systems Biology, Harvard University, 02138, Cambridge, Massachusetts, USA
  • Department of Epidemiology, Harvard School of Public Health, 02115, Boston, Massachusetts, USA
  • Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
  • Departments of Psychiatry and Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, 92093, La Jolla, California, USA
  • Seaver Autism Center and Department of Psychiatry, Mount Sinai School of Medicine, 10029, New York, New York, USA
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 10461, Bronx, New York, USA
  • Department of Genetics, Stanford University, 94305, Stanford, California, USA
  • European Molecular Biology Laboratory, Genome Biology Research Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany
  • Molecular Epidemiology Section, Medical Statistics and Bioinformatics, Leiden University Medical Center, 2333 ZA, The Netherlands
  • Department of Biological Sciences, Louisiana State University, 70803, Baton Rouge, Louisiana, USA
  • Department of Statistics, University of Oxford, Oxford OX1 3TG, UK
  • The Translational Genomics Research Institute, 445 N Fifth Street, 85004, Phoenix, Arizona, USA
  • Center for Biomolecular Science and Engineering, University of California Santa Cruz, 95064, Santa Cruz, California, USA
  • Department of Human Genetics and Howard Hughes Medical Institute, University of Chicago, 60637, Chicago, Illinois, USA
  • Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 94158, San Francisco, California, USA
  • Department of Human Genetics, University of Chicago, 60637, Chicago, Illinois, USA
  • Center for Statistical Genetics and Biostatistics, University of Michigan, 48109, Ann Arbor, Michigan, USA
  • National Heart and Lung Institute, Imperial College London, London SW7 2, UK
  • Centre Nationale de Génotypage, Evry 91000, France
  • Departments of Epidemiology and Biostatistics, Harvard School of Public Health, 02115, Boston, Massachusetts, USA
  • Department of Epidemiology, University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Department of Pediatrics, Faculty of Medicine, University of Montréal, Ste. Justine Hospital Research Centre, Montréal, Québec H3T 1C5, Canada
  • Department of Ecology and Evolutionary Biology, Rice University, 77251, Houston, Texas, USA
  • Department of Medicine, Centre Hospitalier de l’Université de Montréal Research Center, Université de Montréal, Montréal, Québec H2L 2W5, Canada
  • Eccles Institute of Human Genetics, University of Utah School of Medicine, 84112, Salt Lake City, Utah, USA
  • Department of Genome Sciences, University of Washington School of Medicine and Howard Hughes Medical Institute, 98195, Seattle, Washington, USA
  • Department of Computer Science, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada
  • Department of Haematology, University of Cambridge and National Health Service Blood and Transplant, Cambridge CB2 1TN, UK
  • Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva 1211, Switzerland
  • Center for Genome Science, Korea National Institute of Health, 194, Tongil-Lo, Eunpyung-Gu, Seoul 122-701, Korea
  • Program in Computational Biology and Bioinformatics, Yale University, 06520, New Haven, Connecticut, USA
  • Department of Molecular Biophysics and Biochemistry, Yale University, 06520, New Haven, Connecticut, USA
  • Department of Computer Science, Yale University, 06520, New Haven, Connecticut, USA
  • Department of Psychiatry and Behavioral Studies, Stanford University, 94305, Stanford, California, USA
  • Coriell Institute, 403 Haddon Avenue, 08103, Camden, New Jersey, USA
  • Centre for Health, Law and Emerging Technologies, University of Oxford, Oxford OX3 7LF, UK
  • Genetic Alliance, 436 Essex Road, London N1 3QP, UK
  • Center for Medical Ethics and Health Policy, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, Texas, USA
  • Department of Medical History and Bioethics, University of Wisconsin–Madison, 53706, Madison, Wisconsin, USA
  • US National Institutes of Health, Center for Research on Genomics and Global Health, 12 South Drive, 20892, Bethesda, Maryland, USA
  • US National Institutes of Health, National Human Genome Research Institute, 5635 Fishers Lane, 20892, Bethesda, Maryland, USA
  • The George Washington University School of Medicine and Health Sciences, 20037, Washington DC, USA
  • US Food and Drug Administration, 11400 Rockville Pike, 20857, Rockville, Maryland, USA
  • US National Institutes of Health, National Human Genome Research Institute, 31 Center Drive, 20892, Bethesda, Maryland, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature09534

    DOI

    http://dx.doi.org/10.1038/nature09534

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010608717

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20981092


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