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 to a phenotype of interest. We sequenced at high coverage ten "case" genomes 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.
authors.affiliation: Center for Human Genome Variation, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Pelak
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ge
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Maia
authors.forename: Mingfu
authors.initials: M
authors.lastname: Zhu
authors.forename: Jason P
authors.initials: JP
authors.lastname: Smith
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Cirulli
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Dickson
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Gumbs
authors.forename: Erin L
authors.initials: EL
authors.lastname: Heinzen
authors.forename: Anna C
authors.initials: AC
authors.lastname: Need
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Ruzzo
authors.forename: Abanish
authors.initials: A
authors.lastname: Singh
authors.forename: C Ryan
authors.initials: CR
authors.lastname: Campbell
authors.forename: Linda K
authors.initials: LK
authors.lastname: Hong
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Lornsen
authors.forename: Alexander M
authors.initials: AM
authors.lastname: McKenzie
authors.forename: Nara L M
authors.initials: NL
authors.lastname: Sobreira
authors.forename: Julie E
authors.initials: JE
authors.lastname: Hoover-Fong
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Milner
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics; D030541:Databases, Genetic; D005091:Exons / Q000235:genetics; D005169:Factor VIII / Q000235:genetics; D020440:Gene Duplication / Q000235:genetics; D055786:Gene Knockout Techniques; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D006467:Hemophilia A / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D005169:Factor VIII