Abstract
BackgroundArray-based comparative genomic hybridization (aCGH) is a high-throughput method for measuring genome-wide DNA copy number changes. Current aCGH methods have limited resolution, sensitivity and reproducibility. Microarrays for aCGH are available only for a few organisms and combination of aCGH data with expression data is cumbersome.ResultsWe present a novel method of using commercial oligonucleotide expression microarrays for aCGH, enabling DNA copy number measurements and expression profiles to be combined using the same platform. This method yields aCGH data from genomic DNA without complexity reduction at a median resolution of approximately 17,500 base pairs. Due to the well-defined nature of oligonucleotide probes, DNA amplification and deletion can be defined at the level of individual genes and can easily be combined with gene expression data.ConclusionA novel method of gene resolution analysis of copy number variation (graCNV) yields high-resolution maps of DNA copy number changes and is applicable to a broad range of organisms for which commercial oligonucleotide expression microarrays are available. Due to the standardization of oligonucleotide microarrays, graCNV results can reliably be compared between laboratories and can easily be combined with gene expression data using the same platform.
Highlights
Array-based comparative genomic hybridization is a high-throughput method for measuring genome-wide DNA copy number changes
Properties of the U133 Plus 2.0 Expression Array as an Array-based comparative genomic hybridization (aCGH) tool The U133 Plus 2.0 array provides over 54,000 probe sets interrogating the human genome and over 39,000 of the probe sets measure CNVs directly within transcribed genes (Table 1)
Principle components analysis (PCA) of RMA data grouped the normal control DNAs together but separated SK-N-SH/G and SK-N-SH/L (Fig. 1B). These two cell lines were derived from the same cell line (SK-N-SH) and have only been propagated by two different laboratories for approximately ten passages independently
Summary
Array-based comparative genomic hybridization (aCGH) is a high-throughput method for measuring genome-wide DNA copy number changes. ACGH microarrays are commercially available for human and mouse studies only, leaving out other model organisms for DNA copy number studies. 4) The platform should provide small spacing between probes to generate high density maps of CNVs; The only commercially available BAC aCGH array available measures at a median resolution of one megabase [8]. Long oligonucleotide arrays [8,9] and SNP microarrays [10,11] depend on averaging signals from multiple probes [9,10] to eliminate false positive measurements, resulting in decreased resolution. Combining DNA copy number and expression data needs strong bioinformatics support [11]. 7) The analytical procedure should interrogate the entire genome; the DNA labeling protocol for SNP microarrays depends on complexity reduction, leaving out significant parts of the genome from analysis [12,13]
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