A high-quality human reference panel reveals the complexity and distribution of genomic structural variants
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Publication date
2016-10-06
Authors
Hehir-Kwa, Jayne Y.
Marschall, Tobias
Kloosterman, Wigard P.
Francioli, Laurent C
Baaijens, Jasmijn A.
Dijkstra, Louis J.
Abdellaoui, Abdel
Koval, Vyacheslav
Thung, Djie Tjwan
Wardenaar, René
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Article
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Abstract
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 100 bp. 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.
Keywords
Genome informatics, Haplotypes, Next-generation sequencing, Structural variation, General Chemistry, General Biochemistry,Genetics and Molecular Biology, General Physics and Astronomy, Journal Article
Citation
Hehir-Kwa, J Y, Marschall, T, Kloosterman, W P, Francioli, L C, Baaijens, J A, Dijkstra, L J, Abdellaoui, A, Koval, V, Thung, D T, Wardenaar, R, Renkens, I, Coe, B P, Deelen, P, De Ligt, J, Lameijer, E W, Van Dijk, F, Hormozdiari, F, Uitterlinden, A G, Van Duijn, C M, Eichler, E E, De Bakker, P I W, Swertz, M A, Wijmenga, C, Van Ommen, G J B, Slagboom, P E, Boomsma, D I, Schönhuth, A, Ye, K, Guryev, V, Bovenberg, J A, De Craen, A J M, Beekman, M, Hofman, A, Willemsen, G, Wolffenbuttel, B, Platteel, M, Du, Y, Chen, R, Cao, H, Cao, R, Sun, Y, Cao, J S, Neerincx, P B T, Dijkstra, M, Byelas, G, Kanterakis, A, Bot, J, Vermaat, M, Laros, J F, den Dunnen, J T, De Knijff, P, Karssen, L C, Van Leeuwen, E M, Amin, N, Rivadeneira, F, Estrada, K, Hottenga, J-J, Kattenberg, V M, Van Enckevort, D, Mei, H, Santcroos, M, Van Schaik, B D C, Handsaker, R E, McCarroll, S A, Ko, A, Sudmant, P & Nijman, I J 2016, 'A high-quality human reference panel reveals the complexity and distribution of genomic structural variants', Nature Communications [E], vol. 7, 12989. https://doi.org/10.1038/ncomms12989