Dataset Information

Inferring combined CNV/SNP haplotypes from genotype data.

ABSTRACT:

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.

SUBMITTER: Su SY

PROVIDER: S-EPMC2913665 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Publications

Inferring combined CNV/SNP haplotypes from genotype data.

Su Shu-Yi SY Asher Julian E JE Jarvelin Marjo-Riita MR Froguel Phillipe P Blakemore Alexandra I F AI Balding David J DJ Coin Lachlan J M LJ

Bioinformatics (Oxford, England) 20100420 11

<h4>Motivation</h4>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 applica ...[more]

PMID: 20406911

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Project description:This data was generated by ENCODE. If you have questions about the data, contact the submitting laboratory directly (Florencia Pauli mailto:fpauli@hudsonalpha.org). If you have questions about the Genome Browser track associated with this data, contact ENCODE (mailto:genome@soe.ucsc.edu). This track is produced as part of the ENCODE project. The track displays copy number variation (CNV) as determined by the Illumina Human 1M-Duo Infinium HD BeadChip assay and circular binary segmentation (CBS). The Human 1M-Duo contains more than 1,100,000 tagSNP markers and a set of ~60,000 additional CNV-targeted markers. The median spacing between markers is 1.5 kb and the mean spacing is 2.4 kb. The B-allele frequency and genotyping single nucleotide polymorphism (SNP) data generated by the experiment are not displayed, but are available for download from the Downloads page. Where applicable, biological replicates of each cell line are reported separately. Possible uses of the data include correction of copy number in peak-calling for ChIP-seq, transcriptome, DNase hypersensitivity, and methylation determinations. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Isolation of genomic DNA and hybridization: Cells were grown according to the approved ENCODE cell culture protocols by the Myers lab and by other ENCODE production groups. The production group is reported in the metadata. Genomic DNA was isolated using the DNeasy Blood and Tissue Kit (Qiagen). DNA concentration and quality were determined by fluorescence (Invitrogen Quant-iT dsDNA High Sensitivity Kit and Qubit Fluorometer), and 400 nanograms of each sample were hybridized to Illumina 1M-Duo DNA Analysis BeadChips. Processing and Analysis: The genotypes from the 1M-Duo Arrays were ascertained with BeadStudio by using default settings and formatting with the A/B genotype designation for each SNP. Primary QC for each sample was a cut-off at a call rate of 0.95. Copy Number Variation (CNV) analysis was performed with circular binary segmentation (DNAcopy) of the log R ratio values at each probe (Olshen et al., 2004). The parameters used were alpha=0.001, nperm=5000, sd.undo=1. The copy number segments are reported with the mean log R ratio for each chromosomal segment called by CBS. Log ratios of ~-0.2 to -1.5 can be considered heterozygous deletions, < -1.5 homozygous deletions, and > 0.2 amplifications. Primary QC for each sample was SD of < 0.6.

Dataset Information

Inferring combined CNV/SNP haplotypes from genotype data.

Motivation

Results

Availability

Publications

Inferring combined CNV/SNP haplotypes from genotype data.

Similar Datasets

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