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

J.Y. Hehir-Kwa; T. Marschall; W.P. Kloosterman; L.C. Francioli; J.A. Baaijens; L.J. Dijkstra; A. Abdellaoui; V. Koval; D.T. Thung; R. Wardenaar; I. Renkens; B.P. Coe; P. Deelen; J. de Ligt; E.W. Lameijer; F. Dijk; F. Hormozdiari; A.G. Uitterlinden; C.M. van Duijn; E.E. Eichler; P.I.W. Bakker; M.A. Swertz; C. Wijmenga; G.J.B van Ommen; P.E. Slagboom; D.I. Boomsma; A. Schönhuth; K. Ye; V. Guryev

doi:10.1038/ncomms12989

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

J.Y. Hehir-Kwa, T. Marschall, W.P. Kloosterman, L.C. Francioli, J.A. Baaijens, L.J. Dijkstra, A. Abdellaoui, V. Koval, D.T. Thung, R. Wardenaar, I. Renkens, B.P. Coe, P. Deelen, J. de Ligt, E.W. Lameijer, F. Dijk, F. Hormozdiari, A.G. Uitterlinden, C.M. van Duijn, E.E. EichlerP.I.W. Bakker, M.A. Swertz, C. Wijmenga, G.J.B van Ommen, P.E. Slagboom, D.I. Boomsma, A. Schönhuth, K. Ye, V. Guryev

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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.

Original language	English
Article number	12989
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12989
Publication status	Published - 2016

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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., Dijk, F., Hormozdiari, F., Uitterlinden, A. G., van Duijn, C. M., ... Guryev, V. (2016). A high-quality human reference panel reveals the complexity and distribution of genomic structural variants. Nature Communications, 7, Article 12989. https://doi.org/10.1038/ncomms12989

@article{ce42ed82c0f645c08ce7ba85e1932876,

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 = "J.Y. Hehir-Kwa and T. Marschall and W.P. Kloosterman and L.C. Francioli and J.A. Baaijens and L.J. Dijkstra and A. Abdellaoui and V. Koval and D.T. Thung and R. Wardenaar and I. Renkens and B.P. Coe and P. Deelen and {de Ligt}, J. and E.W. Lameijer and F. Dijk and F. Hormozdiari and A.G. Uitterlinden and {van Duijn}, C.M. and E.E. Eichler and P.I.W. Bakker and M.A. Swertz and C. Wijmenga and {van Ommen}, G.J.B and P.E. Slagboom and D.I. Boomsma and A. Sch{\"o}nhuth and K. Ye and V. Guryev",

year = "2016",

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, Dijk, F, Hormozdiari, F, Uitterlinden, AG, van Duijn, CM, Eichler, EE, Bakker, PIW, Swertz, MA, Wijmenga, C, van Ommen, GJB, Slagboom, PE, Boomsma, DI, Schönhuth, A, Ye, K & Guryev, V 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, J.Y.

AU - Marschall, T.

AU - Kloosterman, W.P.

AU - Francioli, L.C.

AU - Baaijens, J.A.

AU - Dijkstra, L.J.

AU - Abdellaoui, A.

AU - Koval, V.

AU - Thung, D.T.

AU - Wardenaar, R.

AU - Renkens, I.

AU - Coe, B.P.

AU - Deelen, P.

AU - de Ligt, J.

AU - Lameijer, E.W.

AU - Dijk, F.

AU - Hormozdiari, F.

AU - Uitterlinden, A.G.

AU - van Duijn, C.M.

AU - Eichler, E.E.

AU - Bakker, P.I.W.

AU - Swertz, M.A.

AU - Wijmenga, C.

AU - van Ommen, G.J.B

AU - Slagboom, P.E.

AU - Boomsma, D.I.

AU - Schönhuth, A.

AU - Ye, K.

AU - Guryev, V.

PY - 2016

Y1 - 2016

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.

U2 - 10.1038/ncomms12989

DO - 10.1038/ncomms12989

M3 - Article

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

Abstract

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