RT Journal Article
SR Electronic
T1 A high-quality reference panel reveals the complexity and distribution of structural genome changes in a human population
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 036897
DO 10.1101/036897
A1 Jayne Y. Hehir-Kwa
A1 Tobias Marschall
A1 Wigard P. Kloosterman
A1 Laurent C. Francioli
A1 Jasmijn A. Baaijens
A1 Louis J. Dijkstra
A1 Abdel Abdellaoui
A1 Vyacheslav Koval
A1 Djie Tjwan Thung
A1 René Wardenaar
A1 Ivo Renkens
A1 Bradley P. Coe
A1 Patrick Deelen
A1 Joep de Ligt
A1 Eric-Wubbo Lameijer
A1 Freerk van Dijk
A1 Fereydoun Hormozdiari
A1 The Genome of the Netherlands Consortium
A1 André G. Uitterlinden
A1 Evan E. Eichler
A1 Paul de Bakker
A1 Morris A. Swertz
A1 Cisca Wijmenga
A1 Gert-Jan B. van Ommen
A1 P. Eline Slagboom
A1 Dorret I. Boomsma
A1 Alexander Schöenhuth
A1 Kai ye
A1 Victor Guryev
YR 2016
UL http://biorxiv.org/content/early/2016/07/02/036897.abstract
AB Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic variation.Here, we analyse whole genome sequencing data of 769 individuals from 250 Dutch families, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels, and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion are previously under reported variants sized between 21 and 100bp. We detect 4 megabases of novel sequence, encoding 11 new transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with SVs and demonstrate that our panel facilitates accurate imputation of SVs in unrelated individuals. Our findings are essential for genome-wide association studies.