Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios

Søren Besenbacher; Siyang Liu; José M G Izarzugaza; Jakob Grove; Kirstine Belling; Jette Bork-Jensen; Shujia Huang; Thomas D Als; Shengting Li; Rachita Yadav; Arcadio Rubio-García; Francesco Lescai; Ditte Demontis; Junhua Rao; Weijian Ye; Thomas Mailund; Rune Møllegaard Friborg; Christian NS Pedersen; Ruiqi Xu; Jihua Sun; Hao Liu; Ou Wang; Xiaofang Cheng; David Flores; Emil Rydza; Kristoffer Rapacki; John Damm Sørensen; Piotr Chmura; David Westergaard; Piotr Dworzynski; Thorkild I A Sørensen; Ole Lund; Torben Hansen; Xun Xu; Ning Li; Lars Bolund; Oluf Pedersen; Hans Eiberg; Anders Krogh; Anders D Børglum; Søren Brunak; Karsten Kristiansen; Mikkel Heide Schierup; Jun Wang; Ramneek Gupta; Palle Villesen; Simon Rasmussen

doi:10.1038/ncomms6969

Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios

Søren Besenbacher, Siyang Liu, José M G Izarzugaza, Jakob Grove, Kirstine Belling, Jette Bork-Jensen, Shujia Huang, Thomas D Als, Shengting Li, Rachita Yadav, Arcadio Rubio-García, Francesco Lescai, Ditte Demontis, Junhua Rao, Weijian Ye, Thomas Mailund, Rune Møllegaard Friborg, Christian NS Pedersen, Ruiqi Xu, Jihua SunHao Liu, Ou Wang, Xiaofang Cheng, David Flores, Emil Rydza, Kristoffer Rapacki, John Damm Sørensen, Piotr Chmura, David Westergaard, Piotr Dworzynski, Thorkild I A Sørensen, Ole Lund, Torben Hansen, Xun Xu, Ning Li, Lars Bolund, Oluf Pedersen, Hans Eiberg, Anders Krogh, Anders D Børglum, Søren Brunak, Karsten Kristiansen, Mikkel Heide Schierup, Jun Wang, Ramneek Gupta, Palle Villesen, Simon Rasmussen

131 Citationer (Scopus)

Abstract

Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e-8 and 1.5e-9 per nucleotide per generation for SNVs and indels, respectively.

Originalsprog	Engelsk
Tidsskrift	Nature Communications
Vol/bind	6
Sider (fra-til)	5969
ISSN	2041-1722
DOI	https://doi.org/10.1038/ncomms6969
Status	Udgivet - 2015

Adgang til dokumentet

10.1038/ncomms6969

Citationsformater

Besenbacher, S., Liu, S., Izarzugaza, J. M. G., Grove, J., Belling, K., Bork-Jensen, J., Huang, S., Als, T. D., Li, S., Yadav, R., Rubio-García, A., Lescai, F., Demontis, D., Rao, J., Ye, W., Mailund, T., Friborg, R. M., Pedersen, C. NS., Xu, R., ... Rasmussen, S. (2015). Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios. Nature Communications, 6, 5969. https://doi.org/10.1038/ncomms6969

Besenbacher, S, Liu, S, Izarzugaza, JMG, Grove, J, Belling, K, Bork-Jensen, J, Huang, S, Als, TD, Li, S, Yadav, R, Rubio-García, A, Lescai, F, Demontis, D, Rao, J, Ye, W, Mailund, T, Friborg, RM, Pedersen, CNS, Xu, R, Sun, J, Liu, H, Wang, O, Cheng, X, Flores, D, Rydza, E, Rapacki, K, Damm Sørensen, J, Chmura, P, Westergaard, D, Dworzynski, P, Sørensen, TIA, Lund, O, Hansen, T, Xu, X, Li, N, Bolund, L, Pedersen, O, Eiberg, H, Krogh, A, Børglum, AD, Brunak, S, Kristiansen, K, Schierup, MH, Wang, J, Gupta, R, Villesen, P & Rasmussen, S 2015, 'Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios', Nature Communications, bind 6, s. 5969. https://doi.org/10.1038/ncomms6969

@article{492b7bb486eb4df19ec3551cc28d2943,

title = "Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios",

abstract = "Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e-8 and 1.5e-9 per nucleotide per generation for SNVs and indels, respectively.",

author = "S{\o}ren Besenbacher and Siyang Liu and Izarzugaza, {Jos{\'e} M G} and Jakob Grove and Kirstine Belling and Jette Bork-Jensen and Shujia Huang and Als, {Thomas D} and Shengting Li and Rachita Yadav and Arcadio Rubio-Garc{\'i}a and Francesco Lescai and Ditte Demontis and Junhua Rao and Weijian Ye and Thomas Mailund and Friborg, {Rune M{\o}llegaard} and Pedersen, {Christian NS} and Ruiqi Xu and Jihua Sun and Hao Liu and Ou Wang and Xiaofang Cheng and David Flores and Emil Rydza and Kristoffer Rapacki and {Damm S{\o}rensen}, John and Piotr Chmura and David Westergaard and Piotr Dworzynski and S{\o}rensen, {Thorkild I A} and Ole Lund and Torben Hansen and Xun Xu and Ning Li and Lars Bolund and Oluf Pedersen and Hans Eiberg and Anders Krogh and B{\o}rglum, {Anders D} and S{\o}ren Brunak and Karsten Kristiansen and Schierup, {Mikkel Heide} and Jun Wang and Ramneek Gupta and Palle Villesen and Simon Rasmussen",

year = "2015",

doi = "10.1038/ncomms6969",

language = "English",

volume = "6",

pages = "5969",

journal = "Nature Communications",

issn = "2041-1722",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios

AU - Besenbacher, Søren

AU - Liu, Siyang

AU - Izarzugaza, José M G

AU - Grove, Jakob

AU - Belling, Kirstine

AU - Bork-Jensen, Jette

AU - Huang, Shujia

AU - Als, Thomas D

AU - Li, Shengting

AU - Yadav, Rachita

AU - Rubio-García, Arcadio

AU - Lescai, Francesco

AU - Demontis, Ditte

AU - Rao, Junhua

AU - Ye, Weijian

AU - Mailund, Thomas

AU - Friborg, Rune Møllegaard

AU - Pedersen, Christian NS

AU - Xu, Ruiqi

AU - Sun, Jihua

AU - Liu, Hao

AU - Wang, Ou

AU - Cheng, Xiaofang

AU - Flores, David

AU - Rydza, Emil

AU - Rapacki, Kristoffer

AU - Damm Sørensen, John

AU - Chmura, Piotr

AU - Westergaard, David

AU - Dworzynski, Piotr

AU - Sørensen, Thorkild I A

AU - Lund, Ole

AU - Hansen, Torben

AU - Xu, Xun

AU - Li, Ning

AU - Bolund, Lars

AU - Pedersen, Oluf

AU - Eiberg, Hans

AU - Krogh, Anders

AU - Børglum, Anders D

AU - Brunak, Søren

AU - Kristiansen, Karsten

AU - Schierup, Mikkel Heide

AU - Wang, Jun

AU - Gupta, Ramneek

AU - Villesen, Palle

AU - Rasmussen, Simon

PY - 2015

Y1 - 2015

N2 - Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e-8 and 1.5e-9 per nucleotide per generation for SNVs and indels, respectively.

AB - Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e-8 and 1.5e-9 per nucleotide per generation for SNVs and indels, respectively.

U2 - 10.1038/ncomms6969

DO - 10.1038/ncomms6969

M3 - Journal article

C2 - 25597990

SN - 2041-1722

VL - 6

SP - 5969

JO - Nature Communications

JF - Nature Communications

ER -

Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater