title: Use of Affymetrix Arrays in the Diagnosis of Gene Copy-Number Variation.
abstract: Diagnosing constitutional pathogenic copy number variants (CNVs) requires detecting submicroscopic segmental chromosomal imbalances. The Affymetrix GeneChip mapping array was one of the initial microarray platforms used to measure duplication and deletion of genetic material in DNA samples. Unlike oligonucleotide microarrays from NimbleGen and Agilent, developed around the same time to infer copy number status for the DNA sequence covered by the probe, the Affymetrix GeneChip system used 25-mer oligonucleotide probes designed to interrogate SNPs. Thus, it was possible to use the Affymetrix 'SNP chips' to both identify SNPs and to identify copy number status. Affymetrix now offers the CytoScan microarray platforms, which are optimized for copy-number analyses, and provides accompanying software. They also offer several other microarray platforms suitable for copy-number analyses. Here we discuss the application of the CytoScan high-density (HD) platform for the detection of genomic imbalance. We provide an overview of the sequence of computational analyses involved in identifying pathogenic CNVs and highlight important parameters for consideration in assessing the pathogenicity of a detected CNV.
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.|University of British Columbia, Department of Medical Genetics, Vancouver, British Columbia, Canada.
authors.forename: Farah R
authors.initials: FR
authors.lastname: Zahir
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.|University of British Columbia, Department of Medical Genetics, Vancouver, British Columbia, Canada.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
mesh_terms: D000483:Alleles; D056915:DNA Copy Number Variations / Q000235:genetics*; D018628:Gene Dosage; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D019656:Loss of Heterozygosity; D009030:Mosaicism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D059629:Signal-To-Noise Ratio; D024182:Uniparental Disomy / Q000175:diagnosis
keywords: Affymetrix; CMA; CytoScan; chromosome aberrations; software