Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

Lasse Maretty; Jacob Malte Jensen; Bent Petersen; Jonas Andreas Sibbesen; Siyang Liu; Palle Villesen; Laurits Skov; Kirstine Christensen Belling; Christian Theil Have; José M G Izarzugaza; Marie Grosjean; Jette Bork-Jensen; Jakob Grove; Thomas D Als; Shujia Huang; Yuqi Chang; Ruiqi Xu; Weijian Ye; Junhua Rao; Xiaosen Guo; Jihua Sun; Hongzhi Cao; Chen Ye; Johan van Beusekom; Thomas Espeseth; Esben Nørgaard Flindt; Rune M Friborg; Anders E Halager; Stephanie Le Hellard; Christina M Hultman; Francesco Lescai; Shengting Li; Ole Lund; Peter Løngren; Thomas Mailund; Maria Luisa Matey-Hernandez; Ole Mors; Christian N S Pedersen; Thomas Sicheritz-Ponten; Patrick F Sullivan; Ali Syed; David Westergaard; Rachita Yadav; Ning Li; Xun Xu; Torben Hansen; Anders Krogh; Lars Bolund; Thorkild I A Sørensen; Oluf Pedersen; Ramneek Gupta; Simon Rasmussen; Søren Besenbacher; Anders D Børglum; Jun Wang; Hans Eiberg; Karsten Kristiansen; Søren Brunak; Mikkel Heide Schierup

doi:10.1038/nature23264

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

Lasse Maretty, Jacob Malte Jensen, Bent Petersen, Jonas Andreas Sibbesen, Siyang Liu, Palle Villesen, Laurits Skov, Kirstine Christensen Belling, Christian Theil Have, José M G Izarzugaza, Marie Grosjean, Jette Bork-Jensen, Jakob Grove, Thomas D Als, Shujia Huang, Yuqi Chang, Ruiqi Xu, Weijian Ye, Junhua Rao, Xiaosen GuoJihua Sun, Hongzhi Cao, Chen Ye, Johan van Beusekom, Thomas Espeseth, Esben Nørgaard Flindt, Rune M Friborg, Anders E Halager, Stephanie Le Hellard, Christina M Hultman, Francesco Lescai, Shengting Li, Ole Lund, Peter Løngren, Thomas Mailund, Maria Luisa Matey-Hernandez, Ole Mors, Christian N S Pedersen, Thomas Sicheritz-Ponten, Patrick F Sullivan, Ali Syed, David Westergaard, Rachita Yadav, Ning Li, Xun Xu, Torben Hansen, Anders Krogh, Lars Bolund, Thorkild I A Sørensen, Oluf Pedersen, Ramneek Gupta, Simon Rasmussen, Søren Besenbacher, Anders D Børglum, Jun Wang, Hans Eiberg, Karsten Kristiansen, Søren Brunak, Mikkel Heide Schierup

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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Abstract

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.

Originalsprog	Engelsk
Tidsskrift	Nature
Vol/bind	548
Nummer	7665
Sider (fra-til)	87-91
Antal sider	5
ISSN	0028-0836
DOI	https://doi.org/10.1038/nature23264
Status	Udgivet - 3 aug. 2017

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10.1038/nature23264

nature23264Forlagets udgivne version, 5,19 MBLicens: CC BY

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Maretty, L., Jensen, J. M., Petersen, B., Sibbesen, J. A., Liu, S., Villesen, P., Skov, L., Belling, K. C., Theil Have, C., Izarzugaza, J. M. G., Grosjean, M., Bork-Jensen, J., Grove, J., Als, T. D., Huang, S., Chang, Y., Xu, R., Ye, W., Rao, J., ... Schierup, M. H. (2017). Sequencing and de novo assembly of 150 genomes from Denmark as a population reference. Nature, 548(7665), 87-91. https://doi.org/10.1038/nature23264

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title = "Sequencing and de novo assembly of 150 genomes from Denmark as a population reference",

abstract = "Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.",

keywords = "Journal Article",

author = "Lasse Maretty and Jensen, {Jacob Malte} and Bent Petersen and Sibbesen, {Jonas Andreas} and Siyang Liu and Palle Villesen and Laurits Skov and Belling, {Kirstine Christensen} and {Theil Have}, Christian and Izarzugaza, {Jos{\'e} M G} and Marie Grosjean and Jette Bork-Jensen and Jakob Grove and Als, {Thomas D} and Shujia Huang and Yuqi Chang and Ruiqi Xu and Weijian Ye and Junhua Rao and Xiaosen Guo and Jihua Sun and Hongzhi Cao and Chen Ye and {van Beusekom}, Johan and Thomas Espeseth and Flindt, {Esben N{\o}rgaard} and Friborg, {Rune M} and Halager, {Anders E} and {Le Hellard}, Stephanie and Hultman, {Christina M} and Francesco Lescai and Shengting Li and Ole Lund and Peter L{\o}ngren and Thomas Mailund and Matey-Hernandez, {Maria Luisa} and Ole Mors and Pedersen, {Christian N S} and Thomas Sicheritz-Ponten and Sullivan, {Patrick F} and Ali Syed and David Westergaard and Rachita Yadav and Ning Li and Xun Xu and Torben Hansen and Anders Krogh and Lars Bolund and S{\o}rensen, {Thorkild I A} and Oluf Pedersen and Ramneek Gupta and Simon Rasmussen and S{\o}ren Besenbacher and B{\o}rglum, {Anders D} and Jun Wang and Hans Eiberg and Karsten Kristiansen and S{\o}ren Brunak and Schierup, {Mikkel Heide}",

year = "2017",

month = aug,

day = "3",

doi = "10.1038/nature23264",

language = "English",

volume = "548",

pages = "87--91",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7665",

}

Maretty, L, Jensen, JM, Petersen, B, Sibbesen, JA, Liu, S, Villesen, P, Skov, L, Belling, KC, Theil Have, C, Izarzugaza, JMG, Grosjean, M, Bork-Jensen, J, Grove, J , Als, TD, Huang, S, Chang, Y, Xu, R, Ye, W, Rao, J, Guo, X, Sun, J, Cao, H, Ye, C, van Beusekom, J, Espeseth, T, Flindt, EN, Friborg, RM, Halager, AE, Le Hellard, S, Hultman, CM, Lescai, F, Li, S, Lund, O, Løngren, P, Mailund, T, Matey-Hernandez, ML, Mors, O , Pedersen, CNS, Sicheritz-Ponten, T, Sullivan, PF, Syed, A, Westergaard, D, Yadav, R, Li, N, Xu, X, Hansen, T, Krogh, A, Bolund, L, Sørensen, TIA, Pedersen, O, Gupta, R, Rasmussen, S, Besenbacher, S , Børglum, AD, Wang, J, Eiberg, H, Kristiansen, K, Brunak, S & Schierup, MH 2017, 'Sequencing and de novo assembly of 150 genomes from Denmark as a population reference', Nature, bind 548, nr. 7665, s. 87-91. https://doi.org/10.1038/nature23264

TY - JOUR

T1 - Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

AU - Maretty, Lasse

AU - Jensen, Jacob Malte

AU - Petersen, Bent

AU - Sibbesen, Jonas Andreas

AU - Liu, Siyang

AU - Villesen, Palle

AU - Skov, Laurits

AU - Belling, Kirstine Christensen

AU - Theil Have, Christian

AU - Izarzugaza, José M G

AU - Grosjean, Marie

AU - Bork-Jensen, Jette

AU - Grove, Jakob

AU - Als, Thomas D

AU - Huang, Shujia

AU - Chang, Yuqi

AU - Xu, Ruiqi

AU - Ye, Weijian

AU - Rao, Junhua

AU - Guo, Xiaosen

AU - Sun, Jihua

AU - Cao, Hongzhi

AU - Ye, Chen

AU - van Beusekom, Johan

AU - Espeseth, Thomas

AU - Flindt, Esben Nørgaard

AU - Friborg, Rune M

AU - Halager, Anders E

AU - Le Hellard, Stephanie

AU - Hultman, Christina M

AU - Lescai, Francesco

AU - Li, Shengting

AU - Lund, Ole

AU - Løngren, Peter

AU - Mailund, Thomas

AU - Matey-Hernandez, Maria Luisa

AU - Mors, Ole

AU - Pedersen, Christian N S

AU - Sicheritz-Ponten, Thomas

AU - Sullivan, Patrick F

AU - Syed, Ali

AU - Westergaard, David

AU - Yadav, Rachita

AU - Li, Ning

AU - Xu, Xun

AU - Hansen, Torben

AU - Krogh, Anders

AU - Bolund, Lars

AU - Sørensen, Thorkild I A

AU - Pedersen, Oluf

AU - Gupta, Ramneek

AU - Rasmussen, Simon

AU - Besenbacher, Søren

AU - Børglum, Anders D

AU - Wang, Jun

AU - Eiberg, Hans

AU - Kristiansen, Karsten

AU - Brunak, Søren

AU - Schierup, Mikkel Heide

PY - 2017/8/3

Y1 - 2017/8/3

N2 - Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.

AB - Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.

KW - Journal Article

U2 - 10.1038/nature23264

DO - 10.1038/nature23264

M3 - Journal article

C2 - 28746312

SN - 0028-0836

VL - 548

SP - 87

EP - 91

JO - Nature

JF - Nature

IS - 7665

ER -

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

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