Systematic assessment of copy number variant detection via genome-wide SNP genotyping

Nat Genet. 2008 Oct;40(10):1199-203. doi: 10.1038/ng.236. Epub 2008 Sep 7.

Abstract

SNP genotyping has emerged as a technology to incorporate copy number variants (CNVs) into genetic analyses of human traits. However, the extent to which SNP platforms accurately capture CNVs remains unclear. Using independent, sequence-based CNV maps, we find that commonly used SNP platforms have limited or no probe coverage for a large fraction of CNVs. Despite this, in 9 samples we inferred 368 CNVs using Illumina SNP genotyping data and experimentally validated over two-thirds of these. We also developed a method (SNP-Conditional Mixture Modeling, SCIMM) to robustly genotype deletions using as few as two SNP probes. We find that HapMap SNPs are strongly correlated with 82% of common deletions, but the newest SNP platforms effectively tag about 50%. We conclude that currently available genome-wide SNP assays can capture CNVs accurately, but improvements in array designs, particularly in duplicated sequences, are necessary to facilitate more comprehensive analyses of genomic variation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Child
  • Chromosomes, Human / genetics*
  • DNA / genetics*
  • Female
  • Gene Amplification
  • Gene Deletion
  • Gene Dosage / genetics*
  • Genetic Variation
  • Genome, Human*
  • Haplotypes / genetics*
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Population Groups / genetics*

Substances

  • DNA