Large multiallelic copy number variations in humans.

Nat Genet
Authors
Keywords
Abstract

Thousands of genomic segments appear to be present in widely varying copy numbers in different human genomes. We developed ways to use increasingly abundant whole-genome sequence data to identify the copy numbers, alleles and haplotypes present at most large multiallelic CNVs (mCNVs). We analyzed 849 genomes sequenced by the 1000 Genomes Project to identify most large (>5-kb) mCNVs, including 3,878 duplications, of which 1,356 appear to have 3 or more segregating alleles. We find that mCNVs give rise to most human variation in gene dosage-seven times the combined contribution of deletions and biallelic duplications-and that this variation in gene dosage generates abundant variation in gene expression. We describe 'runaway duplication haplotypes' in which genes, including HPR and ORM1, have mutated to high copy number on specific haplotypes. We also describe partially successful initial strategies for analyzing mCNVs via imputation and provide an initial data resource to support such analyses.

Year of Publication
2015
Journal
Nat Genet
Volume
47
Issue
3
Pages
296-303
Date Published
2015 Mar
ISSN
1546-1718
URL
DOI
10.1038/ng.3200
PubMed ID
25621458
PubMed Central ID
PMC4405206
Links
Grant list
R01 HG006855 / HG / NHGRI NIH HHS / United States
U01 HG006510 / HG / NHGRI NIH HHS / United States