UNLABELLED: A program package to enable genome-wide association of copy number variants (CNVs) with quantitative phenotypes in families of arbitrary size and complexity. Intensity signals that act as proxies for the number of copies are modeled in a variance component framework and association with traits is assessed through formal likelihood testing. AVAILABILITY AND IMPLEMENTATION: The Java package is made available at www.imperial.ac.uk/medicine/people/m.falchi/. CONTACT: [email protected].

MOTIVATION: Copy number variations (CNVs) are increasingly recognized as an substantial source of individual genetic variation, and hence there is a growing interest in investigating the evolutionary history of CNVs as well as their impact on complex disease susceptibility. CNV/SNP haplotypes are critical for this research, but although many methods have been proposed for inferring integer copy number, few have been designed for inferring CNV haplotypic phase and none of these are applicable at genome-wide scale. Here, we present a method for inferring missing CNV genotypes, predicting CNV allelic configuration and for inferring CNV haplotypic phase from SNP/CNV genotype data. Our method, implemented in the software polyHap v2.0, is based on a hidden Markov model, which models the joint haplotype structure between CNVs and SNPs. Thus, haplotypic phase of CNVs and SNPs are inferred simultaneously. A sampling algorithm is employed to obtain a measure of confidence/credibility of each estimate. RESULTS: We generated diploid phase-known CNV-SNP genotype datasets by pairing male X chromosome CNV-SNP haplotypes. We show that polyHap provides accurate estimates of missing CNV genotypes, allelic configuration and CNV haplotypic phase on these datasets. We applied our method to a non-simulated dataset-a region on Chromosome 2 encompassing a short deletion. The results confirm that polyHap's accuracy extends to real-life datasets. AVAILABILITY: Our method is implemented in version 2.0 of the polyHap software package and can be downloaded from http://www.imperial.ac.uk/medicine/people/l.coin.