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

Research output: Contribution to journalArticlepeer-review

132 Scopus citations


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
Issue number9
StatePublished - Sep 2010

ASJC Scopus subject areas

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


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