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Zaboli, G.* ; Ameur, A.* ; Igl, W.* ; Johansson, A.* ; Hayward, C.* ; Vitart, V.* ; Campbell, S.* ; Zgaga, L.* ; Polasek, O.* ; Schmitz, G.* ; van Duijn, C.M.* ; Oostra, B.* ; Pramstaller, P.* ; Hicks, A.* ; Meitinger, T. ; Rudan, I.* ; Wright, A.* ; Wilson, J.F.* ; Campbell, H.* ; Gyllensten, U* ; EUROSPAN Consortium (*)

Sequencing of high-complexity DNA pools for identification of nucleotide and structural variants in regions associated with complex traits.

Eur. J. Hum. Genet. 20, 77-83 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
We have used targeted genomic sequencing of high-complexity DNA pools based on long-range PCR and deep DNA sequencing by the SOLiD technology. The method was used for sequencing of 286 kb from four chromosomal regions with quantitative trait loci (QTL) influencing blood plasma lipid and uric acid levels in DNA pools of 500 individuals from each of five European populations. The method shows very good precision in estimating allele frequencies as compared with individual genotyping of SNPs (r(2) = 0.95, P < 10(-16)). Validation shows that the method is able to identify novel SNPs and estimate their frequency in high-complexity DNA pools. In our five populations, 17% of all SNPs and 61% of structural variants are not available in the public databases. A large fraction of the novel variants show a limited geographic distribution, with 62% of the novel SNPs and 59% of novel structural variants being detected in only one of the populations. The large number of population-specific novel SNPs underscores the need for comprehensive sequencing of local populations in order to identify the causal variants of human traits.
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Publication type Article: Journal article
Document type Scientific Article
Keywords pooling; next-generation DNA sequencing; SOLiD; SNP; indels
ISSN (print) / ISBN 1018-4813
e-ISSN 1476-5438
Journal European Journal of Human Genetics
Quellenangaben Volume: 20, Issue: 1, Pages: 77-83 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)