PT  - JOURNAL ARTICLE
AU  - Jayne Y. Hehir-Kwa
AU  - Tobias Marschall
AU  - Wigard P. Kloosterman
AU  - Laurent C. Francioli
AU  - Jasmijn A. Baaijens
AU  - Louis Dijkstra
AU  - Abdel Abdellaoui
AU  - Vyacheslav Koval
AU  - Djie Tjwan Thung
AU  - René Wardenaar
AU  - Bradley Coe
AU  - Patrick Deelen
AU  - Joep de Ligt
AU  - Eric-Wubbo Lameijer
AU  - Freerk van Dijk
AU  - Fereydoun Hormozdiari
AU  - Evan E. Eichler
AU  - Paul I.W. de Bakker
AU  - Morris A. Swertz
AU  - Cisca Wijmenga
AU  - Gert-Jan B. van Ommen
AU  - P. Eline Slagboom
AU  - Dorret I. Boomsma
AU  - Genome of the Netherlands Consortium
AU  - Alexander Schöenhuth
AU  - Kai Ye
AU  - Victor Guryev
TI  - A high-quality reference panel reveals the complexity and distribution of structural genome changes in a human population
AID  - 10.1101/036897
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 036897
4099  - http://biorxiv.org/content/early/2016/01/18/036897.short
4100  - http://biorxiv.org/content/early/2016/01/18/036897.full
AB  - Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, current studies on SVs have failed to provide a global view of the full spectrum of SVs and to integrate them into reference panels of genetic variation.Here, we analyzed 769 individuals from 250 Dutch families, whole-genome sequenced at an average coverage of 14.5x, 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 of the structural variants (36%) were discovered in the size range of 21 - 100bp, a size range which remains under reported in many studies. Furthermore, we detected 4 megabases of novel sequence, extending the human pangenome with 11 new active transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with a structural variant and demonstrate that our panel facilitates accurate imputation of SVs into unrelated individuals, which is essential for future genome-wide association studies.