TY - JOUR
T1 - A high-quality human reference panel reveals the complexity and distribution of genomic structural variants
AU - Hehir-Kwa, Jayne Y.
AU - Marschall, Tobias
AU - Kloosterman, Wigard P.
AU - Francioli, Laurent C.
AU - Baaijens, Jasmijn A.
AU - Dijkstra, Louis J.
AU - Abdellaoui, Abdel
AU - Koval, Vyacheslav
AU - Thung, Djie Tjwan
AU - Wardenaar, René
AU - Renkens, Ivo
AU - Coe, Bradley P.
AU - Deelen, Patrick
AU - De Ligt, Joep
AU - Lameijer, Eric Wubbo
AU - Van Dijk, Freerk
AU - Hormozdiari, Fereydoun
AU - Uitterlinden, André G.
AU - Van Duijn, Cornelia M.
AU - Eichler, Evan E.
AU - De Bakker, Paul I.W.
AU - Swertz, Morris A.
AU - Wijmenga, Cisca
AU - Van Ommen, Gert Jan B.
AU - Slagboom, P. Eline
AU - Boomsma, Dorret I.
AU - Schönhuth, Alexander
AU - Ye, Kai
AU - Guryev, Victor
AU - Bovenberg, Jasper A.
AU - De Craen, Anton J.M.
AU - Beekman, Marian
AU - Hofman, Albert
AU - Willemsen, Gonneke
AU - Wolffenbuttel, Bruce
AU - Platteel, Mathieu
AU - Du, Yuanping
AU - Chen, Ruoyan
AU - Cao, Hongzhi
AU - Cao, Rui
AU - Sun, Yushen
AU - Cao, Jeremy Sujie
AU - Neerincx, Pieter B.T.
AU - Dijkstra, Martijn
AU - Byelas, George
AU - Kanterakis, Alexandros
AU - Bot, Jan
AU - Vermaat, Martijn
AU - Laros, Jeroen F.J.
AU - Den Dunnen, Johan T.
AU - De Knijff, Peter
AU - Karssen, Lennart C.
AU - Van Leeuwen, Elisa M.
AU - Amin, Najaf
AU - Rivadeneira, Fernando
AU - Estrada, Karol
AU - Hottenga, Jouke Jan
AU - Kattenberg, V. Mathijs
AU - Van Enckevort, David
AU - Mei, Hailiang
AU - Santcroos, Mark
AU - Van Schaik, Barbera D.C.
AU - Handsaker, Robert E.
AU - McCarroll, Steven A.
AU - Ko, Arthur
AU - Sudmant, Peter
AU - Nijman, Isaac J.
PY - 2016/10/6
Y1 - 2016/10/6
N2 - 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.
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 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.
UR - http://www.scopus.com/inward/record.url?scp=84990859114&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/ncomms12989
DO - https://doi.org/10.1038/ncomms12989
M3 - Article
C2 - 27708267
SN - 2041-1723
VL - 7
JO - Nature communications
JF - Nature communications
M1 - 12989
ER -