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. Eichler; Paul 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.J. 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

doi:10.1038/ncomms12989

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.J. 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

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

75 Citaten (Scopus)

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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.

Originele taal-2	Engels
Artikelnummer	12989
Tijdschrift	Nature Communications
Volume	7
DOI's	https://doi.org/10.1038/ncomms12989
Status	Gepubliceerd - 6 okt. 2016
Extern gepubliceerd	Ja

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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., ... Nijman, I. J. (2016). A high-quality human reference panel reveals the complexity and distribution of genomic structural variants. Nature Communications, 7, Artikel 12989. https://doi.org/10.1038/ncomms12989

@article{dea97c7f74f34178827cc088a4e7c0b5,

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

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.",

author = "Hehir-Kwa, {Jayne Y.} and Tobias Marschall and Kloosterman, {Wigard P.} and Francioli, {Laurent C.} and Baaijens, {Jasmijn A.} and Dijkstra, {Louis J.} and Abdel Abdellaoui and Vyacheslav Koval and Thung, {Djie Tjwan} and Ren{\'e} Wardenaar and Ivo Renkens and Coe, {Bradley P.} and Patrick Deelen and {De Ligt}, Joep and Lameijer, {Eric Wubbo} and {Van Dijk}, Freerk and Fereydoun Hormozdiari and Uitterlinden, {Andr{\'e} G.} and {Van Duijn}, {Cornelia M.} and Eichler, {Evan E.} and {De Bakker}, {Paul I.W.} and Swertz, {Morris A.} and Cisca Wijmenga and {Van Ommen}, {Gert Jan B.} and Slagboom, {P. Eline} and Boomsma, {Dorret I.} and Alexander Sch{\"o}nhuth and Kai Ye and Victor Guryev and Bovenberg, {Jasper A.} and {De Craen}, {Anton J.M.} and Marian Beekman and Albert Hofman and Gonneke Willemsen and Bruce Wolffenbuttel and Mathieu Platteel and Yuanping Du and Ruoyan Chen and Hongzhi Cao and Rui Cao and Yushen Sun and Cao, {Jeremy Sujie} and Neerincx, {Pieter B.T.} and Martijn Dijkstra and George Byelas and Alexandros Kanterakis and Jan Bot and Martijn Vermaat and Laros, {Jeroen F.J.} and {Den Dunnen}, {Johan T.} and {De Knijff}, Peter and Karssen, {Lennart C.} and {Van Leeuwen}, {Elisa M.} and Najaf Amin and Fernando Rivadeneira and Karol Estrada and Hottenga, {Jouke Jan} and Kattenberg, {V. Mathijs} and {Van Enckevort}, David and Hailiang Mei and Mark Santcroos and {Van Schaik}, {Barbera D.C.} and Handsaker, {Robert E.} and McCarroll, {Steven A.} and Arthur Ko and Peter Sudmant and Nijman, {Isaac J.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2016.",

year = "2016",

month = oct,

day = "6",

doi = "10.1038/ncomms12989",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Hehir-Kwa, JY, Marschall, T, Kloosterman, WP, Francioli, LC, Baaijens, JA, Dijkstra, LJ, Abdellaoui, A, Koval, V, Thung, DT, Wardenaar, R, Renkens, I, Coe, BP, Deelen, P, De Ligt, J, Lameijer, EW, Van Dijk, F, Hormozdiari, F, Uitterlinden, AG, Van Duijn, CM, Eichler, EE, De Bakker, PIW, Swertz, MA, Wijmenga, C, Van Ommen, GJB, Slagboom, PE, Boomsma, DI, Schönhuth, A, Ye, K, Guryev, V, Bovenberg, JA, De Craen, AJM, Beekman, M, Hofman, A, Willemsen, G, Wolffenbuttel, B, Platteel, M, Du, Y, Chen, R, Cao, H, Cao, R, Sun, Y, Cao, JS, Neerincx, PBT, Dijkstra, M, Byelas, G, Kanterakis, A, Bot, J, Vermaat, M, Laros, JFJ, Den Dunnen, JT, De Knijff, P, Karssen, LC, Van Leeuwen, EM, Amin, N, Rivadeneira, F, Estrada, K, Hottenga, JJ, Kattenberg, VM, Van Enckevort, D, Mei, H, Santcroos, M, Van Schaik, BDC, Handsaker, RE, McCarroll, SA, Ko, A, Sudmant, P & Nijman, IJ 2016, 'A high-quality human reference panel reveals the complexity and distribution of genomic structural variants', Nature Communications, vol. 7, 12989. https://doi.org/10.1038/ncomms12989

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.

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U2 - 10.1038/ncomms12989

DO - 10.1038/ncomms12989

M3 - Article

C2 - 27708267

AN - SCOPUS:84990859114

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 12989

ER -

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

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