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Microarray Analysis of the Physical Genome

Volume 556 of the series Methods in Molecular Biology™ pp 47-65

Date:

Application of Oligonucleotides Arrays for Coincident Comparative Genomic Hybridization, Ploidy Status and Loss of Heterozygosity Studies in Human Cancers

  • John K. CowellAffiliated withSchool of Medicine, Medical College of Georgia Cancer Center
  • , Ken C. LoAffiliated withRoche NimbleGen, Inc.

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Abstract

Many oligonucleotide arrays comprise of spotted short oligonucleotides from throughout the genome under study. Hybridization of tumor DNA samples to these arrays will provide copy number estimates at each reference point with varying degrees of accuracy. In addition to copy number changes, however, tumors often undergo loss of heterozygosity for specific regions of the genome without copy number changes and these genetic changes can only be identified using arrays that identify polymorphic alleles at each reference point. In addition, because the hybridization intensity can be measured at each of the allelic variants, allelic ratios can be established which give indications of ploidy status in the tumor which is not generally possible using most other oligonucleotide array designs. The only arrays currently available that simultaneously report copy number, ploidy, and loss of heterozygosity are the Affymetrix SNP mapping arrays.

In this review, the features of the SNP mapping arrays are described and computational tools explored which allow the maximum genetic information to be extracted from the experiment. Although the methodologies to generate the SNP data are now well established, approaches to interpret the data are only just being developed. From our experience using these arrays, we provide insights into how to evaluate the SNP data to report copy number changes, loss of heterozygosity, and ploidy in the same tumor samples using a single array.

Key words

SNP mapping arrays comparative genome hybridization loss of heterozygosity allelic ratios CGH visualization tools oligonucleotide arrays