Whole-genome sequence variation, population structure and demographic history of the Dutch population

Laurent C. Francioli, Androniki Menelaou, Sara L. Pulit, Freerk Van Dijk, Pier Francesco Palamara, Clara C. Elbers, Pieter B.T. Neerincx, Kai Ye, Victor Guryev, Wigard P. Kloosterman, Patrick Deelen, Abdel Abdellaoui, Elisabeth M. Van Leeuwen, Mannis Van Oven, Martijn Vermaat, Mingkun Li, Jeroen F.J. Laros, Lennart C. Karssen, Alexandros Kanterakis, Najaf AminJouke Jan Hottenga, Eric Wubbo Lameijer, Mathijs Kattenberg, Martijn Dijkstra, Heorhiy Byelas, Jessica Van Setten, Barbera D.C. Van Schaik, Jan Bot, Isaäc J. Nijman, Ivo Renkens, Tobias Marschall, Alexander Schönhuth, Jayne Y. Hehir-Kwa, Robert E. Handsaker, Paz Polak, Mashaal Sohail, Dana Vuzman, Fereydoun Hormozdiari, David Van Enckevort, Hailiang Mei, Vyacheslav Koval, Matthijs H. Moed, KJoeri Van Der Velde, Fernando Rivadeneira, Karol Estrada, Carolina Medina-Gomez, Aaron Isaacs, Steven A. McCarroll, Marian Beekman, Anton J. Mde Craen, H. Eka D. Suchiman, Albert Hofman, Ben Oostra, André G. Uitterlinden, Gonneke Willemsen, Mathieu Platteel, Jan H. Veldink, Leonard H. Van Den Berg, Steven J. Pitts, Shobha Potluri, Purnima Sundar, David R. Cox, Shamil R. Sunyaev, Johan T. Den Dunnen, Mark Stoneking, Peter De Knijff, Manfred Kayser, Qibin Li, Yingrui Li, Yuanping Du, Ruoyan Chen, Hongzhi Cao, Ning Li, Sujie Cao, Jun Wang, Jasper A. Bovenberg, Itsik Pe'er, P. Eline Slagboom, Cornelia M. Van Duijn, Dorret I. Boomsma, Gert Jan B. Van Ommen, Paul I.W. De Bakker, Morris A. Swertz, Cisca Wijmenga

Research output: Contribution to journalArticle

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Abstract

Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (∼13×) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies.

Original languageEnglish (US)
Pages (from-to)818-825
Number of pages8
JournalNature Genetics
Volume46
Issue number8
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Francioli, L. C., Menelaou, A., Pulit, S. L., Van Dijk, F., Palamara, P. F., Elbers, C. C., Neerincx, P. B. T., Ye, K., Guryev, V., Kloosterman, W. P., Deelen, P., Abdellaoui, A., Van Leeuwen, E. M., Van Oven, M., Vermaat, M., Li, M., Laros, J. F. J., Karssen, L. C., Kanterakis, A., ... Wijmenga, C. (2014). Whole-genome sequence variation, population structure and demographic history of the Dutch population. Nature Genetics, 46(8), 818-825. https://doi.org/10.1038/ng.3021