Microarray Techniques to Analyze Copy-Number Alterations in Genomic DNA: Array Comparative Genomic Hybridization and Single-Nucleotide Polymorphism Array

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Microarray Techniques to Analyze Copy-Number Alterations in Genomic DNA: Array Comparative Genomic Hybridization and Single-Nucleotide Polymorphism Array Károly Szuhai, Maarten Vermeer Journal of Investigative Dermatology Volume 135, Issue 10, Pages 1-5 (October 2015) DOI: 10.1038/jid.2015.308 Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Overview of genomic array-based procedures. The left panel shows array-comparative genomic hybridization (array CGH), whereas the right panel shows single-nucleotide polymorphism (SNP) array. Array CGH utilizes differentially labeled test and reference DNAs, whereas SNP array uses labeled single test samples. In both cases, samples are mixed with repeat suppressor C0t-1 DNA and hybridized to detection chips. After hybridization and stringent washing, array chips are scanned by a fluorescence laser scanner and intensity values are further processed. Resulting data files are analyzed for changes in chromosomes and DNA base positions. The resolution of the array is largely determined by the reporter probe density. The lower left panel shows superimposed results using either an ~3.5-kb bacterial artificial chromosome (BAC) probe array (black dots) or a 244-kb oligonucleotide probe array (gray dots). The blue arrowhead indicates a small triplicated region undetected by the BAC array. The lower right panel shows results from a SNP array showing the copy number of the displayed chromosome (lower inset), indicating no copy-number alteration. In the upper inset, B-allele frequency is displayed. Because most of the SNP should be heterozygous, here the allele frequency should be expected to be 0.5. Loss of heterozygosity (LOH) would lead to either the lack of B alleles (0) or two B alleles (1.0). The red arrowheads mark large regions of LOH without corresponding copy-number alterations, a phenomenon known as copy number-neutral LOH. Journal of Investigative Dermatology 2015 135, 1-5DOI: (10.1038/jid.2015.308) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Array CGH identified a high level of amplification and homozygous losses in primary cutaneous large B-cell lymphomas. (a) Genome-wide overview of multiple primary cutaneous large B-cell lymphoma cases. (b) The most frequent high level of amplification involved the chromosome 2p16.1 region where BCL11A and REL genes reside. (c) Interphase: fluorescence in situ hybridization (FISH) verification of the REL amplification using REL (green) and CDK4 (red) region-specific probes. The numerous loci of green signal correspond to the amplification detected by array CGH. Reprinted with permission from Dijkman et al. (2006). Journal of Investigative Dermatology 2015 135, 1-5DOI: (10.1038/jid.2015.308) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Journal of Investigative Dermatology 2015 135, 1-5DOI: (10. 1038/jid Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Journal of Investigative Dermatology 2015 135, 1-5DOI: (10. 1038/jid Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions