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Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11901-11906. Epub 2016 Oct 4.

Deep sequencing of 10,000 human genomes.

Author information

1
Human Longevity Inc., San Diego, CA 92121; J. Craig Venter Institute, La Jolla, CA 92037.
2
Human Longevity Inc., San Diego, CA 92121; Human Longevity Inc., Mountain View, CA 94041.
3
Human Longevity Inc., San Diego, CA 92121.
4
Human Longevity Singapore Pte. Ltd., Singapore 138542.
5
Human Longevity Inc., San Diego, CA 92121; Human Longevity Singapore Pte. Ltd., Singapore 138542.
6
Human Longevity Inc., San Diego, CA 92121; J. Craig Venter Institute, La Jolla, CA 92037; jcventer@humanlongevity.com.

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.

KEYWORDS:

genomics; human genetic diversity; noncoding genome

PMID:
27702888
PMCID:
PMC5081584
DOI:
10.1073/pnas.1613365113
[Indexed for MEDLINE]
Free PMC Article

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