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

Authors:

Nat Genet 2014 Aug 29;46(8):818-25. Epub 2014 Jun 29.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.3021DOI Listing
August 2014
5 Reads

Publication Analysis

Top Keywords

characterization genetic
8
whole-genome sequencing
8
genetic variation
8
gonl project
8
migrations consistent
4
coverage ∼13×
4
intermediate coverage
4
deletions intermediate
4
characterization structural
4
∼13× trio
4
trio design
4
enabled extensive
4
extensive characterization
4
consistent historical
4
design enabled
4
ancient migrations
4
insertions deletions
4
constructed haplotype
4
sea level
4
frequency alleles
4

References

(Supplied by CrossRef)

ES Lander et al.
Nature 2001

DA Hinds et al.
Science 2005

TA Manolio et al.
Nat. Rev. Genet. 2013

PM Visscher et al.
Am. J. Hum. Genet. 2012

J McClellan et al.
Cell 2010

G Gibson et al.
Nat. Rev. Genet. 2011

DB Goldstein et al.
Nat. Rev. Genet. 2013

J Weischenfeldt et al.
Nat. Rev. Genet. 2013

Similar Publications