@article {785,
	title = {Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes.},
	journal = {Nat Commun},
	volume = {11},
	year = {2020},
	month = {2020 05 27},
	pages = {2539},
	abstract = {<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.</p>},
	keywords = {CpG Islands, Databases, Genetic, DNA Mutational Analysis, Exome, Genetic Variation, Genome, Human, Humans, Mutation},
	issn = {2041-1723},
	doi = {10.1038/s41467-019-12438-5},
	author = {Wang, Qingbo and Pierce-Hoffman, Emma and Cummings, Beryl B and Alf{\"o}ldi, Jessica and Francioli, Laurent C and Gauthier, Laura D and Hill, Andrew J and O{\textquoteright}Donnell-Luria, Anne H and Karczewski, Konrad J and MacArthur, Daniel G}
}
