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

Søren Besenbacher; Siyang Liu; Jose Maria Gonzalez-Izarzugaza; Jakob Grove; Kirstine G Belling; Jette Bork-Jensen; Shujia Huang; Thomas Damm Als; Shengting Li; Rachita Yadav; Arcadio Rubio García; Francesco Lescai; Ditte Demontis; Junhua Rao; Weijian Ye; Thomas Mailund; Rune Møllegaard Friborg; Christian N. S. Pedersen; Ruiqi Xu; Jihua Sun; Hao Liu; Ou Wang; Xiaofang Cheng; David Flores; Emil Karol Rydza; Kristoffer Rapacki; John Damm Sørensen; Piotr Jaroslaw 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 H 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, Jose Maria Gonzalez-Izarzugaza, Jakob Grove, Kirstine G Belling, Jette Bork-Jensen, Shujia Huang, Thomas Damm Als, Shengting Li, Rachita Yadav, Arcadio Rubio García, Francesco Lescai, Ditte Demontis, Junhua Rao, Weijian Ye, Thomas Mailund, Rune Møllegaard Friborg, Christian N. S. Pedersen, Ruiqi Xu, Jihua SunHao Liu, Ou Wang, Xiaofang Cheng, David Flores, Emil Karol Rydza, Kristoffer Rapacki, John Damm Sørensen, Piotr Jaroslaw 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 H Schierup, Jun Wang, Ramneek Gupta, Palle Villesen, Simon Rasmussen

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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.

Original language	English
Article number	5969
Journal	Nature Communications
Volume	6
Number of pages	9
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms6969
Publication status	Published - Jan 2015

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Besenbacher, S., Liu, S., Gonzalez-Izarzugaza, J. M., Grove, J., Belling, K. G., 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., Møllegaard Friborg, R., Pedersen, C. N. S., Xu, R., ... Rasmussen, S. (2015). Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios. Nature Communications, 6, Article 5969. https://doi.org/10.1038/ncomms6969

Besenbacher, S, Liu, S, Gonzalez-Izarzugaza, JM, Grove, J, Belling, KG, Bork-Jensen, J, Huang, S, Als, TD, Li, S, Yadav, R, Rubio García, A, Lescai, F, Demontis, D, Rao, J, Ye, W, Mailund, T, Møllegaard Friborg, R, Pedersen, CNS, Xu, R, Sun, J, Liu, H, Wang, O, Cheng, X, Flores, D, Rydza, EK, Rapacki, K, Sørensen, JD, Chmura, PJ, 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, vol. 6, 5969. https://doi.org/10.1038/ncomms6969

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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 Gonzalez-Izarzugaza, {Jose Maria} and Jakob Grove and Belling, {Kirstine G} and Jette Bork-Jensen and Shujia Huang and Als, {Thomas Damm} and Shengting Li and Rachita Yadav and {Rubio Garc{\'i}a}, Arcadio and Francesco Lescai and Ditte Demontis and Junhua Rao and Weijian Ye and Thomas Mailund and {M{\o}llegaard Friborg}, Rune and Pedersen, {Christian N. S.} and Ruiqi Xu and Jihua Sun and Hao Liu and Ou Wang and Xiaofang Cheng and David Flores and Rydza, {Emil Karol} and Kristoffer Rapacki and S{\o}rensen, {John Damm} and Chmura, {Piotr Jaroslaw} 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 H} and Jun Wang and Ramneek Gupta and Palle Villesen and Simon Rasmussen",

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

AU - Besenbacher, Søren

AU - Liu, Siyang

AU - Gonzalez-Izarzugaza, Jose Maria

AU - Grove, Jakob

AU - Belling, Kirstine G

AU - Bork-Jensen, Jette

AU - Huang, Shujia

AU - Als, Thomas Damm

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 - Møllegaard Friborg, Rune

AU - Pedersen, Christian N. S.

AU - Xu, Ruiqi

AU - Sun, Jihua

AU - Liu, Hao

AU - Wang, Ou

AU - Cheng, Xiaofang

AU - Flores, David

AU - Rydza, Emil Karol

AU - Rapacki, Kristoffer

AU - Sørensen, John Damm

AU - Chmura, Piotr Jaroslaw

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 H

AU - Wang, Jun

AU - Gupta, Ramneek

AU - Villesen, Palle

AU - Rasmussen, Simon

PY - 2015/1

Y1 - 2015/1

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 - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 5969

ER -

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

Abstract

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