A high-quality human reference panel reveals the complexity and distribution of genomic structural variants

Jayne Y. Hehir-Kwa, Tobias Marschall, Wigard P. Kloosterman, Laurent C. Francioli, Jasmijn A. Baaijens, Louis J. Dijkstra, Abdel Abdellaoui, Vyacheslav Koval, Djie Tjwan Thung, René Wardenaar, Ivo Renkens, Bradley P. Coe, Patrick Deelen, Joep De Ligt, Eric Wubbo Lameijer, Freerk Van Dijk, Fereydoun Hormozdiari, André G. Uitterlinden, Cornelia M. Van Duijn, Evan E. EichlerPaul I.W. De Bakker, Morris A. Swertz, Cisca Wijmenga, Gert Jan B Van Ommen, P. Eline Slagboom, Dorret I. Boomsma, Alexander Schönhuth*, Kai Ye, Victor Guryev, Jasper A. Bovenberg, Anton J M De Craen, Marian Beekman, Albert Hofman, Gonneke Willemsen, Bruce Wolffenbuttel, Mathieu Platteel, Yuanping Du, Ruoyan Chen, Hongzhi Cao, Rui Cao, Yushen Sun, Jeremy Sujie Cao, Pieter B T Neerincx, Martijn Dijkstra, George Byelas, Alexandros Kanterakis, Jan Bot, Martijn Vermaat, Jeroen F. Laros, Johan T. den Dunnen, Peter De Knijff, Lennart C. Karssen, Elisa M. Van Leeuwen, Najaf Amin, Fernando Rivadeneira, Karol Estrada, Jouke-Jan Hottenga, V. Mathijs Kattenberg, David Van Enckevort, Hailiang Mei, Mark Santcroos, Barbera D C Van Schaik, Robert E. Handsaker, Steven A. McCarroll, Arthur Ko, Peter Sudmant, Isaac J. Nijman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Article number12989
JournalNature Communications [E]
Publication statusPublished - 6 Oct 2016


  • Genome informatics
  • Haplotypes
  • Next-generation sequencing
  • Structural variation


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