Use of Affymetrix Arrays in the Diagnosis of Gene Copy‐Number Variation

Farah R. Zahir1, Marco A. Marra1

1 University of British Columbia, Department of Medical Genetics, Vancouver, British Columbia
Publication Name:  Current Protocols in Human Genetics
Unit Number:  Unit 8.13
DOI:  10.1002/0471142905.hg0813s85
Online Posting Date:  April, 2015
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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. © 2015 by John Wiley & Sons, Inc.

Keywords: CMA; chromosome aberrations; software; CytoScan; Affymetrix

     
 
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Table of Contents

  • Introduction
  • Overview of Informatics Steps in Analyzing Microarray Data
  • Background Information
  • Summary
  • Figures
     
 
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Materials

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Literature Cited

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Internet Resources
  http://www.affymetrix.com
  Affymetrix Web site containing information about the microarrays, wet lab protocols for preparing DNA, procedures for processing and scanning chips, and annotation files for analyses.
  http://www.tcag.ca
  Web site for the Database of Genomic Variants (DGV; also known as the Toronto Database). Lists known copy number polymorphisms from the literature.
  http://omim.org
  Online Mendelian Inheritance of Man database: A manually curated database of comprehensive gene and genetic‐region centric information.
  https://decipher.sanger.ac.uk/
  Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources: A repository of pathogenic CNVs and clinical information. A validated user name and password is used to access clinical data.
  http://www.iccg.org/
  International Collaboration for Clinical Genomics:Database of CNVs detected by clinical and accredited molecular testing laboratories worldwide.
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