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 Sobreira, Julie E Hoover FongJoshua D. Milner, Ruth Ottman, Barton F. Haynes, James J. Goedert, David B. Goldstein

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article numbere1001111
JournalPLoS Genetics
Volume6
Issue number9
DOIs
Publication statusPublished - Sep 2010

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ASJC Scopus subject areas

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

Cite this

Pelak, K., Shianna, K. V., Ge, D., Maia, J. M., Zhu, M., Smith, J. P., ... Goldstein, D. B. (2010). The characterization of twenty sequenced human genomes. PLoS Genetics, 6(9), [e1001111]. https://doi.org/10.1371/journal.pgen.1001111