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

LC Francioli, A Menelaou, SL Pulit, Femke Dijk, PF Palamara, CC Elbers, PBT Neerincx, K Ye, V Guryev, WP Kloosterman, P Deelen, A Abdellaoui, Elisa Leeuwen, Mannis Oven, M Vermaat, M Li, JFJ Laros, Lennart Karssen, A Kanterakis, Najaf AminJJ (Jouke Jan) Hottenga, EW Lameijer, M Kattenberg, M Dijkstra, H Byelas, J Van Settenl, BDC van Schaik, J Bot, IJ Nijman, I Renkens, T Marscha, A Schonhuth, JY Hehir-Kwa, RE Handsaker, P Polak, M Sohail, D Vuzman, F Hormozdiari, D van Enckevort, Hailang Mei, Slavik Koval, MTH Moed, KJ Van der Velde, Fernando Rivadeneira, Karol Estrada Gil, C Medina-Gomez, Aaron Isaacs, SA McCarroll, M Beekrnan, AJM de Craen, HED Suchiman, Bert Hofman, Ben Oostra, André Uitterlinden, G Willemsen, M Plattee, JH Veldink, LH van den Berg, SJ Pitts, S Potluri, P Sundar, DR Cox, SR Sunyaev, JT Dunnen, M Stoneking, P de Knijff, Manfred Kayser, QB Li, YR Li, YP Du, Ruoqing Chen, H Cao, N (Nan) Li, S Cao, Johnny Wang, JA Bovenberg, I Peer, PE (Eline) Slagboom, Cornelia Duijn, DI Boomsma, GJB van Ommen, PIW de Bakker, MA Swertz, C Wijmenga

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464 Citations (Scopus)

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 (similar to 13x) 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 languageUndefined/Unknown
Pages (from-to)818-825
Number of pages8
JournalNature Genetics
Volume46
Issue number8
DOIs
Publication statusPublished - 2014

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