Analysis Of The Genotyping Data
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10.6 years ago
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Dear all, I have genotyping data of 1 person(Done with affymetrix SNP6.0 array)and I want to check the homozygote regions to find if they include one of the genes related to the disease of that individual. Is it possible to find the homozygote regions for just 1 person(without genotyping data of the other family members) according to IBS by homozygosity mapper or IBDfinder? and if not,is there any program that I can analyse the data to find the homozygote region?

genotyping affymetrix snp array copynumber • 4.7k views
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This could be a good and relevant question - if revised. Are you looking for LOH regions or for instances where the SNP genotype is AA, CC, GG, or TT? Clarify and then you'll receive clear answers.

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10.6 years ago

Perhaps you mean that you wish to identify regions exhibiting loss of heterozygosity (LOH), perhaps copy number neutral LOH, also known as uniparental disomy (UPD). If so, then yes, this should be possible using tools available from Affymetrix and elsewhere. Once the regions of LOH are identified you can determine whether any of your genes of interest overlap with them.

LOH is determined by examining the genotype calls at successive SNP positions represented on the SNP 6.0 array. There are many tools for analyzing these arrays. For example, you could try: APT-CopyNumber provided by Affymetrix.

apt-copynumber-workflow is a program for find de novo copy number changes and Loss of Heterozygosity (LOH) on a per sample basis with respect to a reference set of samples. The copy number algorithm it implements assumes that the reference set comprises a mix of normal human males (with XY chromosomes) and normal human females (with XX chromosomes). The algorithms assume that in this reference for each autosomal marker (SNP or Copy Number probe) the predominant Copy Number is 2, and for the sex chromosomes the copy number is determined by the gender.

apt-copynumber-workflow implements two distinct workflows, a batch worflow that uses as a reference the set of CEL files that are input; and conceptually, a single-sample workflow that compares each CEL file to a pre-computed reference. For efficiency of computation the "single-sample workflow" operates on a set of input CEL files at a time, but the output for any CEL file is unaffected by any of the other CEL files.

You might also consider the oligo and crlmm packages of Bioconductor.

Another option is the Aroma project. They have an Affy SNP6 resource page and a Vignette for processing of a single array.

Further background information from Affymetrix's website:

Copy number changes aren't the only genomic change with important implications for disease. Loss of heterozygosity (LOH) is also an important genomic aberration. Regions with LOH can extend several megabases (Mb), encompassing multiple genetic loci or even whole chromosome arms. In its pathogenic form, LOH in a cell represents the loss of normal function (wild-type function) of one allele of a gene in which the other allele was already inactivated. The inactivation of the remaining wild-type allele arises from complex genomic events such as multi-locus deletion, gene conversion, mitotic recombination, and non-disjunction. The genomic change is carried forward during mitotic recombination between homologous chromosomes, reminiscent of recombination during meiosis, in which the functional region is lost.

The combination of copy number with LOH means that regions of copy-neutral LOH (also known as uniparental disomy, or UPD) can easily be identified. These events, extremely important in both cancer samples and general cytogenetic cases, cannot be detected using traditional cytogenetic methods such as FISH or comparative genomic hybridization (CGH).

The figure below highlights the SNP Array 6.0's ability to measure structural changes (copy number) and sequence variations (UPD) across the entire genome. Regions of LOH greater than 3 Mb are summarized in the red block. The LOH region is copy-number neutral, as illustrated by the blue data points of log2 ratios and copy number state. This entire chromosome would be considered structurally normal, yet it is severely abnormal from a sequence perspective.

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