Mapping copy number variation by population-scale genome sequencing. Academic Article uri icon

Overview

MeSH

  • Gene Duplication
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Mutagenesis, Insertional
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • Sequence Deletion

MeSH Major

  • DNA Copy Number Variations
  • Genetics, Population
  • Genome, Human
  • Genomics

abstract

  • Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.

authors

publication date

  • February 3, 2011

has subject area

  • DNA Copy Number Variations
  • Gene Duplication
  • Genetic Predisposition to Disease
  • Genetics, Population
  • Genome, Human
  • Genomics
  • Genotype
  • Humans
  • Mutagenesis, Insertional
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • Sequence Deletion

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3077050

Digital Object Identifier (DOI)

  • 10.1038/nature09708

PubMed ID

  • 21293372

Additional Document Info

start page

  • 59

end page

  • 65

volume

  • 470

number

  • 7332