cnvHap: an integrative population and haplotype-based multiplatform model of SNPs and CNVs.

Nat Methods 2010 Jul 30;7(7):541-6. Epub 2010 May 30.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St. Mary's Hospital, London, UK.

Although genome-wide association studies have uncovered single-nucleotide polymorphisms (SNPs) associated with complex disease, these variants account for a small portion of heritability. Some contribution to this 'missing heritability' may come from copy-number variants (CNVs), in particular rare CNVs; but assessment of this contribution remains challenging because of the difficulty in accurately genotyping CNVs, particularly small variants. We report a population-based approach for the identification of CNVs that integrates data from multiple samples and platforms. Our algorithm, cnvHap, jointly learns a chromosome-wide haplotype model of CNVs and cluster-based models of allele intensity at each probe. Using data for 50 French individuals assayed on four separate platforms, we found that cnvHap correctly detected at least 14% more deleted and 50% more amplified genotypes than PennCNV or QuantiSNP, with an 82% and 115% improvement for aberrations containing <10 probes. Combining data from multiple platforms additionally improved sensitivity.

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http://dx.doi.org/10.1038/nmeth.1466DOI Listing
July 2010
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References

(Supplied by CrossRef)

D Meyre et al.
Nat. Genet. 2009

R Sladek et al.
Nature 2007

E Zeggini et al.
Nat. Genet. 2008

EH Cook et al.
Nature 2008

RG Walters et al.
Nature 2010

TJ Aitman et al.
Nature 2006

SJ Diskin et al.
Nature 2009

SA McCarroll et al.
Nat. Genet. 2008

CJ Willer et al.
Nat. Genet. 2009

DA Kleinjan et al.
Am. J. Hum. Genet. 2005

BE Stranger et al.
Science 2007

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