An integrated map of structural variation in 2,504 human genomes

Peter H. Sudmant; Tobias Rausch; Eugene J. Gardner; Robert E. Handsaker; Alexej Abyzov; John Huddleston; Yan Zhang; Kai Ye; Goo Jun; Markus His Yang Fritz; Miriam K. Konkel; Ankit Malhotra; Adrian M. Stütz; Xinghua Shi; Francesco Paolo Casale; Jieming Chen; Fereydoun Hormozdiari; Gargi Dayama; Ken Chen; Maika Malig; Mark J.P. Chaisson; Klaudia Walter; Sascha Meiers; Seva Kashin; Erik Garrison; Adam Auton; Hugo Y.K. Lam; Xinmeng Jasmine Mu; Can Alkan; Danny Antaki; Taejeong Bae; Eliza Cerveira; Peter Chines; Zechen Chong; Laura Clarke; Elif Dal; Li Ding; Sarah Emery; Xian Fan; Madhusudan Gujral; Fatma Kahveci; Jeffrey M. Kidd; Yu Kong; Eric Wubbo Lameijer; Shane McCarthy; Paul Flicek; Richard A. Gibbs; Gabor Marth; Christopher E. Mason; Androniki Menelaou; Donna M. Muzny; Bradley J. Nelson; Amina Noor; Nicholas F. Parrish; Matthew Pendleton; Andrew Quitadamo; Benjamin Raeder; Eric E. Schadt; Mallory Romanovitch; Andreas Schlattl; Robert Sebra; Andrey A. Shabalin; Andreas Untergasser; Jerilyn A. Walker; Min Wang; Fuli Yu; Chengsheng Zhang; Jing Zhang; Xiangqun Zheng-Bradley; Wanding Zhou; Thomas Zichner; Jonathan Sebat; Mark A. Batzer; Steven A. McCarroll; Ryan E. Mills; Mark B. Gerstein; Ali Bashir; Oliver Stegle; Scott E. Devine; Charles Lee; Evan E. Eichler; Jan O. Korbel

doi:10.1038/nature15394

An integrated map of structural variation in 2,504 human genomes

Peter H. Sudmant, Tobias Rausch, Eugene J. Gardner, Robert E. Handsaker, Alexej Abyzov, John Huddleston, Yan Zhang, Kai Ye, Goo Jun, Markus His Yang Fritz, Miriam K. Konkel, Ankit Malhotra, Adrian M. Stütz, Xinghua Shi, Francesco Paolo Casale, Jieming Chen, Fereydoun Hormozdiari, Gargi Dayama, Ken Chen, Maika MaligMark J.P. Chaisson, Klaudia Walter, Sascha Meiers, Seva Kashin, Erik Garrison, Adam Auton, Hugo Y.K. Lam, Xinmeng Jasmine Mu, Can Alkan, Danny Antaki, Taejeong Bae, Eliza Cerveira, Peter Chines, Zechen Chong, Laura Clarke, Elif Dal, Li Ding, Sarah Emery, Xian Fan, Madhusudan Gujral, Fatma Kahveci, Jeffrey M. Kidd, Yu Kong, Eric Wubbo Lameijer, Shane McCarthy, Paul Flicek, Richard A. Gibbs, Gabor Marth, Christopher E. Mason, Androniki Menelaou, Donna M. Muzny, Bradley J. Nelson, Amina Noor, Nicholas F. Parrish, Matthew Pendleton, Andrew Quitadamo, Benjamin Raeder, Eric E. Schadt, Mallory Romanovitch, Andreas Schlattl, Robert Sebra, Andrey A. Shabalin, Andreas Untergasser, Jerilyn A. Walker, Min Wang, Fuli Yu, Chengsheng Zhang, Jing Zhang, Xiangqun Zheng-Bradley, Wanding Zhou, Thomas Zichner, Jonathan Sebat, Mark A. Batzer, Steven A. McCarroll, Ryan E. Mills, Mark B. Gerstein, Ali Bashir, Oliver Stegle, Scott E. Devine, Charles Lee, Evan E. Eichler, Jan O. Korbel

Genetics

Research output: Contribution to journal › Article › peer-review

1443 Scopus citations

Abstract

Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.

Original language	English (US)
Pages (from-to)	75-81
Number of pages	7
Journal	Nature
Volume	526
Issue number	7571
DOIs	https://doi.org/10.1038/nature15394
State	Published - Sep 30 2015

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nature15394

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Sudmant, P. H., Rausch, T., Gardner, E. J., Handsaker, R. E., Abyzov, A., Huddleston, J., Zhang, Y., Ye, K., Jun, G., Fritz, M. H. Y., Konkel, M. K., Malhotra, A., Stütz, A. M., Shi, X., Casale, F. P., Chen, J., Hormozdiari, F., Dayama, G., Chen, K., ... Korbel, J. O. (2015). An integrated map of structural variation in 2,504 human genomes. Nature, 526(7571), 75-81. https://doi.org/10.1038/nature15394

Sudmant, PH, Rausch, T, Gardner, EJ, Handsaker, RE, Abyzov, A, Huddleston, J, Zhang, Y, Ye, K, Jun, G, Fritz, MHY, Konkel, MK, Malhotra, A, Stütz, AM, Shi, X, Casale, FP, Chen, J, Hormozdiari, F, Dayama, G, Chen, K, Malig, M, Chaisson, MJP, Walter, K, Meiers, S, Kashin, S, Garrison, E, Auton, A, Lam, HYK, Mu, XJ, Alkan, C, Antaki, D, Bae, T, Cerveira, E, Chines, P, Chong, Z, Clarke, L, Dal, E, Ding, L, Emery, S, Fan, X, Gujral, M, Kahveci, F, Kidd, JM, Kong, Y, Lameijer, EW, McCarthy, S, Flicek, P, Gibbs, RA, Marth, G, Mason, CE, Menelaou, A, Muzny, DM, Nelson, BJ, Noor, A, Parrish, NF, Pendleton, M, Quitadamo, A, Raeder, B, Schadt, EE, Romanovitch, M, Schlattl, A, Sebra, R, Shabalin, AA, Untergasser, A, Walker, JA, Wang, M, Yu, F, Zhang, C, Zhang, J, Zheng-Bradley, X, Zhou, W, Zichner, T, Sebat, J, Batzer, MA, McCarroll, SA, Mills, RE, Gerstein, MB, Bashir, A, Stegle, O, Devine, SE, Lee, C, Eichler, EE & Korbel, JO 2015, 'An integrated map of structural variation in 2,504 human genomes', Nature, vol. 526, no. 7571, pp. 75-81. https://doi.org/10.1038/nature15394

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title = "An integrated map of structural variation in 2,504 human genomes",

abstract = "Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.",

author = "Sudmant, {Peter H.} and Tobias Rausch and Gardner, {Eugene J.} and Handsaker, {Robert E.} and Alexej Abyzov and John Huddleston and Yan Zhang and Kai Ye and Goo Jun and Fritz, {Markus His Yang} and Konkel, {Miriam K.} and Ankit Malhotra and St{\"u}tz, {Adrian M.} and Xinghua Shi and Casale, {Francesco Paolo} and Jieming Chen and Fereydoun Hormozdiari and Gargi Dayama and Ken Chen and Maika Malig and Chaisson, {Mark J.P.} and Klaudia Walter and Sascha Meiers and Seva Kashin and Erik Garrison and Adam Auton and Lam, {Hugo Y.K.} and Mu, {Xinmeng Jasmine} and Can Alkan and Danny Antaki and Taejeong Bae and Eliza Cerveira and Peter Chines and Zechen Chong and Laura Clarke and Elif Dal and Li Ding and Sarah Emery and Xian Fan and Madhusudan Gujral and Fatma Kahveci and Kidd, {Jeffrey M.} and Yu Kong and Lameijer, {Eric Wubbo} and Shane McCarthy and Paul Flicek and Gibbs, {Richard A.} and Gabor Marth and Mason, {Christopher E.} and Androniki Menelaou and Muzny, {Donna M.} and Nelson, {Bradley J.} and Amina Noor and Parrish, {Nicholas F.} and Matthew Pendleton and Andrew Quitadamo and Benjamin Raeder and Schadt, {Eric E.} and Mallory Romanovitch and Andreas Schlattl and Robert Sebra and Shabalin, {Andrey A.} and Andreas Untergasser and Walker, {Jerilyn A.} and Min Wang and Fuli Yu and Chengsheng Zhang and Jing Zhang and Xiangqun Zheng-Bradley and Wanding Zhou and Thomas Zichner and Jonathan Sebat and Batzer, {Mark A.} and McCarroll, {Steven A.} and Mills, {Ryan E.} and Gerstein, {Mark B.} and Ali Bashir and Oliver Stegle and Devine, {Scott E.} and Charles Lee and Eichler, {Evan E.} and Korbel, {Jan O.}",

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AU - Sudmant, Peter H.

AU - Rausch, Tobias

AU - Gardner, Eugene J.

AU - Handsaker, Robert E.

AU - Abyzov, Alexej

AU - Huddleston, John

AU - Zhang, Yan

AU - Ye, Kai

AU - Jun, Goo

AU - Fritz, Markus His Yang

AU - Konkel, Miriam K.

AU - Malhotra, Ankit

AU - Stütz, Adrian M.

AU - Shi, Xinghua

AU - Casale, Francesco Paolo

AU - Chen, Jieming

AU - Hormozdiari, Fereydoun

AU - Dayama, Gargi

AU - Chen, Ken

AU - Malig, Maika

AU - Chaisson, Mark J.P.

AU - Walter, Klaudia

AU - Meiers, Sascha

AU - Kashin, Seva

AU - Garrison, Erik

AU - Auton, Adam

AU - Lam, Hugo Y.K.

AU - Mu, Xinmeng Jasmine

AU - Alkan, Can

AU - Antaki, Danny

AU - Bae, Taejeong

AU - Cerveira, Eliza

AU - Chines, Peter

AU - Chong, Zechen

AU - Clarke, Laura

AU - Dal, Elif

AU - Ding, Li

AU - Emery, Sarah

AU - Fan, Xian

AU - Gujral, Madhusudan

AU - Kahveci, Fatma

AU - Kidd, Jeffrey M.

AU - Kong, Yu

AU - Lameijer, Eric Wubbo

AU - McCarthy, Shane

AU - Flicek, Paul

AU - Gibbs, Richard A.

AU - Marth, Gabor

AU - Mason, Christopher E.

AU - Menelaou, Androniki

AU - Muzny, Donna M.

AU - Nelson, Bradley J.

AU - Noor, Amina

AU - Parrish, Nicholas F.

AU - Pendleton, Matthew

AU - Quitadamo, Andrew

AU - Raeder, Benjamin

AU - Schadt, Eric E.

AU - Romanovitch, Mallory

AU - Schlattl, Andreas

AU - Sebra, Robert

AU - Shabalin, Andrey A.

AU - Untergasser, Andreas

AU - Walker, Jerilyn A.

AU - Wang, Min

AU - Yu, Fuli

AU - Zhang, Chengsheng

AU - Zhang, Jing

AU - Zheng-Bradley, Xiangqun

AU - Zhou, Wanding

AU - Zichner, Thomas

AU - Sebat, Jonathan

AU - Batzer, Mark A.

AU - McCarroll, Steven A.

AU - Mills, Ryan E.

AU - Gerstein, Mark B.

AU - Bashir, Ali

AU - Stegle, Oliver

AU - Devine, Scott E.

AU - Lee, Charles

AU - Eichler, Evan E.

AU - Korbel, Jan O.

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An integrated map of structural variation in 2,504 human genomes

Abstract

ASJC Scopus subject areas

UN SDGs

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