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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes

Author

  • Qingbo Wang
  • Leif Groop
  • C Haiman
  • Olle Melander
  • Peter M Nilsson
  • Daniel G MacArthur

Summary, in English

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

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension
  • Internal Medicine - Epidemiology

Publishing year

2020

Language

English

Publication/Series

Nature Communications

Volume

11

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Hypertension
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 2041-1723