A high-quality human reference panel reveals the complexity and distribution of genomic structural variants View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10-06

AUTHORS

Jayne Y. Hehir-Kwa, Tobias Marschall, Wigard P. Kloosterman, Laurent C. Francioli, Jasmijn A. Baaijens, Louis J. Dijkstra, Abdel Abdellaoui, Vyacheslav Koval, Djie Tjwan Thung, René Wardenaar, Ivo Renkens, Bradley P. Coe, Patrick Deelen, Joep de Ligt, Eric-Wubbo Lameijer, Freerk van Dijk, Fereydoun Hormozdiari, Jasper A. Bovenberg, Anton J. M. de Craen, Marian Beekman, Albert Hofman, Gonneke Willemsen, Bruce Wolffenbuttel, Mathieu Platteel, Yuanping Du, Ruoyan Chen, Hongzhi Cao, Rui Cao, Yushen Sun, Jeremy Sujie Cao, Pieter B. T. Neerincx, Martijn Dijkstra, George Byelas, Alexandros Kanterakis, Jan Bot, Martijn Vermaat, Jeroen F. J. Laros, Johan T. den Dunnen, Peter de Knijff, Lennart C. Karssen, Elisa M. van Leeuwen, Najaf Amin, Fernando Rivadeneira, Karol Estrada, Jouke-Jan Hottenga, V. Mathijs Kattenberg, David van Enckevort, Hailiang Mei, Mark Santcroos, Barbera D. C. van Schaik, Robert E. Handsaker, Steven A. McCarroll, Arthur Ko, Peter Sudmant, Isaac J. Nijman, André G. Uitterlinden, Cornelia M. van Duijn, Evan E. Eichler, Paul I. W. de Bakker, Morris A. Swertz, Cisca Wijmenga, Gert-Jan B. van Ommen, P. Eline Slagboom, Dorret I. Boomsma, Alexander Schönhuth, Kai Ye, Victor Guryev

ABSTRACT

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic variation. Here, we analyse whole genome sequencing data of 769 individuals from 250 Dutch families, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels, and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion are previously under reported variants sized between 21 and 100 bp. We detect 4 megabases of novel sequence, encoding 11 new transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with SVs and demonstrate that our panel facilitates accurate imputation of SVs in unrelated individuals. More... »

PAGES

12989

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    7

    Author Affiliations

  • Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen 6525GA, The Netherlands
  • Max Plank Institute for Informatics, Saarbrücken 66123, Germany
  • Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands
  • Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
  • Life Sciences Group, Centrum Wiskunde & Informatica, Amsterdam 1098XG, The Netherlands
  • Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam 1081BT, The Netherlands
  • Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands
  • Groningen Bioinformatics Centre, University of Groningen, Groningen 9747AG, The Netherlands
  • Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle 98105, USA
  • University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen 9700RB, The Netherlands
  • Department of Human Genetics, Leiden University Medical Center, Leiden 2300RC, The Netherlands
  • Genomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen 9700RB, The Netherlands
  • Legal Pathways Institute for Health and Bio Law, Aerdenhout 2111XS, The Netherlands
  • Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden 2300RC, The Netherlands
  • Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands
  • Department of Endocrinology University Medical Center Groningen, Groningen 9700RB, The Netherlands
  • BGI, Shenzhen 518083, China
  • Leiden Institute of Advanced Computer Science, Leiden University, Leiden 2300RC, The Netherlands
  • Netherlands Bioinformatics Centre, Nijmegen 6245GA, The Netherlands
  • Leiden Genome Technology Center, Leiden University Medical Center, Leiden 2300RC, The Netherlands
  • Department of Clinical Epidemiology, Amsterdam Medical Center, Amsterdam 1090GE, The Netherlands
  • Department of Genetics, Harvard Medical School, Boston 02115, USA
  • Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584CG, The Netherlands
  • The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China
  • European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713AD, The Netherlands
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms12989

    DOI

    http://dx.doi.org/10.1038/ncomms12989

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1008018203

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27708267


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    820 grid-institutes:grid.66859.34 schema:alternateName Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    821 schema:name Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
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    824 The Broad Institute, Cambridge, Massachusetts 02142, USA
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    826 grid-institutes:grid.7692.a schema:alternateName Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584CG, The Netherlands
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    828 schema:name Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584CG, The Netherlands
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