Method
Recently, platforms for generating high-resolution karyotypes in silico from disrupted DNA have emerged, such as array comparative genomic hybridization (arrayCGH) and SNP arrays. Conceptually, the arrays are composed of hundreds to millions of probes which are complementary to a region of interest in the genome. The disrupted DNA from the test sample is fragmented, labeled, and hybridized to the array. The hybridization signal intensities for each probe are used by specialized software to generate a log2ratio of test/normal for each probe on the array. Knowing the address of each probe on the array and the address of each probe in the genome, the software lines up the probes in chromosomal order and reconstructs the genome in silico (Fig 2 and 3).
Virtual karyotypes have dramatically higher resolution than conventional cytogenetics. The actual resolution will depend on the density of probes on the array. Currently, the Affymetrix SNP6.0 is the highest density commercially available array for virtual karyotyping applications. It contains 1.8 million polymorphic and non-polymorphic markers for a practical resolution of 10-20kb—about the size of a gene. This is approximately 1000-fold greater resolution than karyotypes obtained from conventional cytogenetics.
Virtual karyotypes can be performed on germline samples for constitutional disorders, and clinical testing is available from dozens of CLIA certified laboratories (GeneTests.org). Virtual karyotyping can also be done on fresh or formalin-fixed paraffin-embedded tumors. CLIA-certified laboratories offering testing on tumors include Creighton Medical Laboratories (fresh and paraffin embedded tumor samples) and CombiMatrix Molecular Diagnostics (fresh tumor samples).
Read more about this topic: Virtual Karyotype
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