Zoom-In Array Comparative Genomic Hybridization (aCGH) to Detect Germline Rearrangements in Cancer Susceptibility Genes
Disease predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements, including deletions or duplications that are challenging, to detect and characterize using standard PCR-based mutation screening methods. Such rearrangements range from single exons up to hundreds of kilobases of sequence in size. Array-based comparative genomic hybridization (aCGH) has evolved as a powerful technique to detect copy number alterations on a genome-wide scale. However, the conventional genome-wide approach of aCGH still provides only limited information about copy number status for individual exons. Custom-designed aCGH arrays focused on only a few target regions (zoom-in aCGH) may circumvent this drawback. Benefits of zoom-in aCGH include the possibility to target almost any region in the genome, and an unbiased coverage of exonic and intronic sequence facilitating convenient design of primers for sequence determination of the breakpoints. Furthermore, zoom-in aCGH can be streamlined for a particular application, for example, focusing on breast cancer susceptibility genes, with increased capacity using multiformat design.
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