title: Deep sequencing of 10,000 human genomes.
abstract: We report on the sequencing of 10,545 human genomes at 30×-40× coverage with an emphasis on quality metrics and novel variant and sequence discovery. We find that 84% of an individual human genome can be sequenced confidently. This high-confidence region includes 91.5% of exon sequence and 95.2% of known pathogenic variant positions. We present the distribution of over 150 million single-nucleotide variants in the coding and noncoding genome. Each newly sequenced genome contributes an average of 8,579 novel variants. In addition, each genome carries on average 0.7 Mb of sequence that is not found in the main build of the hg38 reference genome. The density of this catalog of variation allowed us to construct high-resolution profiles that define genomic sites that are highly intolerant of genetic variation. These results indicate that the data generated by deep genome sequencing is of the quality necessary for clinical use.
authors.affiliation: Human Longevity Inc., San Diego, CA 92121; J. Craig Venter Institute, La Jolla, CA 92037.
authors.forename: Amalio
authors.identifier: 0000-0001-6290-7677
authors.initials: A
authors.lastname: Telenti
authors.affiliation: Human Longevity Inc., San Diego, CA 92121; Human Longevity Inc., Mountain View, CA 94041.
authors.forename: Levi C T
authors.initials: LC
authors.lastname: Pierce
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: William H
authors.initials: WH
authors.lastname: Biggs
authors.affiliation: Human Longevity Inc., San Diego, CA 92121; J. Craig Venter Institute, La Jolla, CA 92037.
authors.forename: Julia
authors.initials: J
authors.lastname: di Iulio
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Emily H M
authors.initials: EH
authors.lastname: Wong
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Fabani
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Ewen F
authors.initials: EF
authors.lastname: Kirkness
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Moustafa
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Naisha
authors.initials: N
authors.lastname: Shah
authors.affiliation: Human Longevity Singapore Pte. Ltd., Singapore 138542.
authors.forename: Chao
authors.initials: C
authors.lastname: Xie
authors.affiliation: Human Longevity Singapore Pte. Ltd., Singapore 138542.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Brewerton
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Bulsara
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Chad
authors.initials: C
authors.lastname: Garner
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Gary
authors.initials: G
authors.lastname: Metzker
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Efren
authors.initials: E
authors.lastname: Sandoval
authors.affiliation: Human Longevity Inc., San Diego, CA 92121.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Perkins
authors.affiliation: Human Longevity Inc., San Diego, CA 92121; Human Longevity Inc., Mountain View, CA 94041.
authors.forename: Franz J
authors.initials: FJ
authors.lastname: Och
authors.affiliation: Human Longevity Inc., San Diego, CA 92121; Human Longevity Singapore Pte. Ltd., Singapore 138542.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Turpaz
authors.affiliation: Human Longevity Inc., San Diego, CA 92121; J. Craig Venter Institute, La Jolla, CA 92037; jcventer@humanlongevity.com.
authors.forename: J Craig
authors.initials: JC
authors.lastname: Venter
mesh_terms: D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D020506:Untranslated Regions; D000073336:Whole Genome Sequencing
chemical_list: D020506:Untranslated Regions
keywords: genomics; human genetic diversity; noncoding genome