An exome sequencing pipeline for identifying and genotyping common CNVs associated with disease with application to psoriasis

Bioinformatics. 2012 Sep 15;28(18):i370-i374. doi: 10.1093/bioinformatics/bts379.

Abstract

Motivation: Despite the prevalence of copy number variation (CNV) in the human genome, only a handful of confirmed associations have been reported between common CNVs and complex disease. This may be partially attributed to the difficulty in accurately genotyping CNVs in large cohorts using array-based technologies. Exome sequencing is now widely being applied to case-control cohorts and presents an exciting opportunity to look for common CNVs associated with disease.

Results: We developed ExoCNVTest: an exome sequencing analysis pipeline to identify disease-associated CNVs and to generate absolute copy number genotypes at putatively associated loci. Our method re-discovered the LCE3B_LCE3C CNV association with psoriasis (P-value = 5 × 10e-6) while controlling inflation of test statistics (λ < 1). ExoCNVTest-derived absolute CNV genotypes were 97.4% concordant with PCR-derived genotypes at this locus.

Availability and implementation: ExoCNVTest has been implemented in Java and R and is freely available from www1.imperial.ac.uk/medicine/people/l.coin/.

Contact: [email protected] or [email protected].

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • DNA Copy Number Variations*
  • Exome*
  • Genome, Human
  • Genotype
  • Humans
  • Psoriasis / genetics*
  • Sequence Analysis, DNA*