Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes
書誌事項
- 公開日
- 2020-05-27
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/s41467-019-12438-5
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title> <jats:p>Multi-nucleotide variants (MNVs), defined as two or more nearby variants existing on the same haplotype in an individual, are a clinically and biologically important class of genetic variation. However, existing tools typically do not accurately classify MNVs, and understanding of their mutational origins remains limited. Here, we systematically survey MNVs in 125,748 whole exomes and 15,708 whole genomes from the Genome Aggregation Database (gnomAD). We identify 1,792,248 MNVs across the genome with constituent variants falling within 2 bp distance of one another, including 18,756 variants with a novel combined effect on protein sequence. Finally, we estimate the relative impact of known mutational mechanisms - CpG deamination, replication error by polymerase zeta, and polymerase slippage at repeat junctions - on the generation of MNVs. Our results demonstrate the value of haplotype-aware variant annotation, and refine our understanding of genome-wide mutational mechanisms of MNVs.</jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 11 (1), 2539-, 2020-05-27
Springer Science and Business Media LLC
