Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

A high-quality reference panel reveals the complexity and distribution of structural genome changes in a human population

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, The Genome of the Netherlands Consortium, André G. Uitterlinden, Evan E. Eichler, Paul de Bakker, Morris A. Swertz, Cisca Wijmenga, Gert-Jan B. van Ommen, P. Eline Slagboom, Dorret I. Boomsma, Alexander Schöenhuth, Kai ye, Victor Guryev
doi: https://doi.org/10.1101/036897
Jayne Y. Hehir-Kwa
1Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, 6525GA, The Netherlands.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tobias Marschall
2Center for Bioinformatics, Saarland University, Saarbrücken, 66123, Germany
3Max-Planck-Institute for Informatics, Saarbrücken, 66123, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wigard P. Kloosterman
4Center for Molecular Medicine, Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laurent C. Francioli
4Center for Molecular Medicine, Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands
5Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA02114, USA; The Broad Institute, Cambridge, MA02142, USA
6Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA02142, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jasmijn A. Baaijens
7Life Sciences Group, Centrum Wiskunde & Informatica, Amsterdam, 1098XG, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Louis J. Dijkstra
7Life Sciences Group, Centrum Wiskunde & Informatica, Amsterdam, 1098XG, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abdel Abdellaoui
8Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, 1081BT, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vyacheslav Koval
9Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3000CA, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Djie Tjwan Thung
1Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, 6525GA, The Netherlands.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
René Wardenaar
10European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, 9713AD, The Netherlands
11Groningen Bioinformatics Centre, University of Groningen, Groningen, 9747AG, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ivo Renkens
4Center for Molecular Medicine, Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bradley P. Coe
12Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, 98105, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick Deelen
13University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, 9700RB, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joep de Ligt
4Center for Molecular Medicine, Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric-Wubbo Lameijer
14Department of Human Genetics, Leiden University Medical Center, Leiden, 2300RC, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Freerk van Dijk
13University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, 9700RB, The Netherlands
15Genomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, 9700RB, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fereydoun Hormozdiari
12Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, 98105, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
16A complete list of consortium authors appears at the end of this article
André G. Uitterlinden
9Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3000CA, The Netherlands
17Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3000CA, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Evan E. Eichler
12Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, 98105, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul de Bakker
4Center for Molecular Medicine, Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands
18Department of Epidemiology, Julius Center for Health Sciences and Primary Care
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Morris A. Swertz
15Genomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, 9700RB, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cisca Wijmenga
13University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, 9700RB, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gert-Jan B. van Ommen
14Department of Human Genetics, Leiden University Medical Center, Leiden, 2300RC, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. Eline Slagboom
19Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, 2300RC, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dorret I. Boomsma
8Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, 1081BT, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander Schöenhuth
7Life Sciences Group, Centrum Wiskunde & Informatica, Amsterdam, 1098XG, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: a.schoenhuth@cwi.nl kaiye@xjtu.edu.cn kv.guryev@umcg.nl
Kai ye
20The Genome Institute, Washington University, St. Louis, MO 63108, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: a.schoenhuth@cwi.nl kaiye@xjtu.edu.cn kv.guryev@umcg.nl
Victor Guryev
10European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, 9713AD, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: a.schoenhuth@cwi.nl kaiye@xjtu.edu.cn kv.guryev@umcg.nl
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

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 100bp. 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. Our findings are essential for genome-wide association studies.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted July 02, 2016.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
A high-quality reference panel reveals the complexity and distribution of structural genome changes in a human population
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
A high-quality reference panel reveals the complexity and distribution of structural genome changes in a human population
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, The Genome of the Netherlands Consortium, André G. Uitterlinden, Evan E. Eichler, Paul de Bakker, Morris A. Swertz, Cisca Wijmenga, Gert-Jan B. van Ommen, P. Eline Slagboom, Dorret I. Boomsma, Alexander Schöenhuth, Kai ye, Victor Guryev
bioRxiv 036897; doi: https://doi.org/10.1101/036897
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
A high-quality reference panel reveals the complexity and distribution of structural genome changes in a human population
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, The Genome of the Netherlands Consortium, André G. Uitterlinden, Evan E. Eichler, Paul de Bakker, Morris A. Swertz, Cisca Wijmenga, Gert-Jan B. van Ommen, P. Eline Slagboom, Dorret I. Boomsma, Alexander Schöenhuth, Kai ye, Victor Guryev
bioRxiv 036897; doi: https://doi.org/10.1101/036897

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4655)
  • Biochemistry (10309)
  • Bioengineering (7629)
  • Bioinformatics (26208)
  • Biophysics (13454)
  • Cancer Biology (10631)
  • Cell Biology (15354)
  • Clinical Trials (138)
  • Developmental Biology (8458)
  • Ecology (12761)
  • Epidemiology (2067)
  • Evolutionary Biology (16777)
  • Genetics (11365)
  • Genomics (15411)
  • Immunology (10557)
  • Microbiology (25063)
  • Molecular Biology (10163)
  • Neuroscience (54132)
  • Paleontology (398)
  • Pathology (1656)
  • Pharmacology and Toxicology (2878)
  • Physiology (4318)
  • Plant Biology (9206)
  • Scientific Communication and Education (1582)
  • Synthetic Biology (2543)
  • Systems Biology (6757)
  • Zoology (1453)