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

Laurent C Francioli, Andronild Menelaou, Sara L Pulit, Freerk Van Dijk, Pier Francesco Palamara, Clara C Elbers, Pieter BT Neerincx, Kai Ye, Victor Guryev, Wigard P Kloosterman

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

518 Citaten (Scopus)


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.

Originele taal-2Ongedefinieerd/onbekend
Pagina's (van-tot)818-825
Aantal pagina's8
TijdschriftNature Genetics
Nummer van het tijdschrift8
StatusGepubliceerd - 2014
Extern gepubliceerdJa

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