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

L.C. Francioli, A. Menelaou, S.L. Pulit, F. Dijk, P.F. Palamara, C.C. Elbers, P.B.T. Neerincx, K. Ye, V. Guryev, W.P. Kloosterman, P. Deelen, A. Abdellaoui, E. van Leeuwen, M. van Oven, M. Vermaat, M. Li, J.F.J. Laros, L.C. Karssen, A. Kanterakis, N. AminE.W. Lameijer, V.M. Kattenberg, M. Dijkstra, H. Byelas, J. van Setten, B.D.C. van Schaik, J. Bot, I.J. Nijman, I. Renkens, T. Marschall, A. Schönhuth, J.Y. Hehir-Kwa, R.E. Handsaker, P. Polak, M. Sohail, D. Vuzman, F. Hormozdiari, D. van Enckevort, H. Mei, V. Koval, M.H. Moed, K.J. van der Velde, F. Rivadeneira, K. Estrada, C. Medina-Gomez, A. Isaacs, S.A. McCarroll, M. Beekman, A.J. de Craen, H.E.D. Suchiman, A. Hofman, B.A. Oostra, A.G. Uitterlinden, G. Willemsen, M. Platteel, J.H. Veldink, L.H. Van den Berg, S.J. Pitts, S. Potluri, P. Sundar, D.R. Cox, S.R. Sunyaev, J.T. den Dunnen, M. Stoneking, P. de Knijff, M. Kayser, Q. Li, Y. Li, Y. Du, R. Chen, H. Cao, N. Li, S. Cao, J. Wang, J.A. Bovenberg, I. Pe'er, P.E. Slagboom, C.M. van Duijn, D.I. Boomsma, G.J.B van Ommen, P.I.W. Bakker, M. Swertz, C. Wijmenga

Research output: Contribution to JournalArticleAcademicpeer-review

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. © 2014 Nature America, Inc.
Original languageEnglish
Pages (from-to)818-825
Number of pages8
JournalNature Genetics
Volume46
Issue number8
DOIs
Publication statusPublished - 2014

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    Francioli, L. C., Menelaou, A., Pulit, S. L., Dijk, F., Palamara, P. F., Elbers, C. C., ... 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