title: Systematic assessment of copy number variant detection via genome-wide SNP genotyping.
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.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. coopergm@u.washington.edu
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cooper
authors.forename: Troy
authors.initials: T
authors.lastname: Zerr
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Kidd
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
mesh_terms: D002648:Child; D002877:Chromosomes, Human / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D018628:Gene Dosage / Q000235:genetics*; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics*
chemical_list: D004247:DNA
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