The characterization of twenty sequenced human genomes

Kimberly Pelak; Kevin V. Shianna; Dongliang Ge; Jessica M. Maia; Mingfu Zhu; Jason P. Smith; Elizabeth T. Cirulli; Jacques Fellay; Samuel P. Dickson; Curtis E. Gumbs; Erin L. Heinzen; Anna C. Need; Elizabeth K. Ruzzo; Abanish Singh; C. Ryan Campbell; Linda K. Hong; Katharina A. Lornsen; Alexander M. McKenzie; Nara L.M. Sobreira; Julie E. Hoover-Fong; Joshua D. Milner; Ruth Ottman; Barton F. Haynes; James J. Goedert; David B. Goldstein

doi:10.1371/journal.pgen.1001111

The characterization of twenty sequenced human genomes

Kimberly Pelak, Kevin V. Shianna, Dongliang Ge, Jessica M. Maia, Mingfu Zhu, Jason P. Smith, Elizabeth T. Cirulli, Jacques Fellay, Samuel P. Dickson, Curtis E. Gumbs, Erin L. Heinzen, Anna C. Need, Elizabeth K. Ruzzo, Abanish Singh, C. Ryan Campbell, Linda K. Hong, Katharina A. Lornsen, Alexander M. McKenzie, Nara L.M. Sobreira, Julie E. Hoover-FongJoshua D. Milner, Ruth Ottman, Barton F. Haynes, James J. Goedert, David B. Goldstein

School of Medicine

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

132 Scopus citations

Abstract

We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute. We sequenced at high coverage ten "case" genome to a phenotype of interests from individuals with severe hemophilia A and ten "control" genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.

Original language	English (US)
Article number	e1001111
Journal	PLoS genetics
Volume	6
Issue number	9
DOIs	https://doi.org/10.1371/journal.pgen.1001111
State	Published - Sep 2010

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

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Pelak, K., Shianna, K. V., Ge, D., Maia, J. M., Zhu, M., Smith, J. P., Cirulli, E. T., Fellay, J., Dickson, S. P., Gumbs, C. E., Heinzen, E. L., Need, A. C., Ruzzo, E. K., Singh, A., Campbell, C. R., Hong, L. K., Lornsen, K. A., McKenzie, A. M., Sobreira, N. L. M., ... Goldstein, D. B. (2010). The characterization of twenty sequenced human genomes. PLoS genetics, 6(9), Article e1001111. https://doi.org/10.1371/journal.pgen.1001111

Pelak, K, Shianna, KV, Ge, D, Maia, JM, Zhu, M, Smith, JP, Cirulli, ET, Fellay, J, Dickson, SP, Gumbs, CE, Heinzen, EL, Need, AC, Ruzzo, EK, Singh, A, Campbell, CR, Hong, LK, Lornsen, KA, McKenzie, AM, Sobreira, NLM , Hoover-Fong, JE, Milner, JD, Ottman, R, Haynes, BF, Goedert, JJ & Goldstein, DB 2010, 'The characterization of twenty sequenced human genomes', PLoS genetics, vol. 6, no. 9, e1001111. https://doi.org/10.1371/journal.pgen.1001111

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title = "The characterization of twenty sequenced human genomes",

abstract = "We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute. We sequenced at high coverage ten {"}case{"} genome to a phenotype of interests from individuals with severe hemophilia A and ten {"}control{"} genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.",

author = "Kimberly Pelak and Shianna, {Kevin V.} and Dongliang Ge and Maia, {Jessica M.} and Mingfu Zhu and Smith, {Jason P.} and Cirulli, {Elizabeth T.} and Jacques Fellay and Dickson, {Samuel P.} and Gumbs, {Curtis E.} and Heinzen, {Erin L.} and Need, {Anna C.} and Ruzzo, {Elizabeth K.} and Abanish Singh and Campbell, {C. Ryan} and Hong, {Linda K.} and Lornsen, {Katharina A.} and McKenzie, {Alexander M.} and Sobreira, {Nara L.M.} and Hoover-Fong, {Julie E.} and Milner, {Joshua D.} and Ruth Ottman and Haynes, {Barton F.} and Goedert, {James J.} and Goldstein, {David B.}",

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AU - Shianna, Kevin V.

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AU - Smith, Jason P.

AU - Cirulli, Elizabeth T.

AU - Fellay, Jacques

AU - Dickson, Samuel P.

AU - Gumbs, Curtis E.

AU - Heinzen, Erin L.

AU - Need, Anna C.

AU - Ruzzo, Elizabeth K.

AU - Singh, Abanish

AU - Campbell, C. Ryan

AU - Hong, Linda K.

AU - Lornsen, Katharina A.

AU - McKenzie, Alexander M.

AU - Sobreira, Nara L.M.

AU - Hoover-Fong, Julie E.

AU - Milner, Joshua D.

AU - Ottman, Ruth

AU - Haynes, Barton F.

AU - Goedert, James J.

AU - Goldstein, David B.

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The characterization of twenty sequenced human genomes

Abstract

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