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METHODS AND TECHNOLOGIES

Array-based comparative genomic hybridization (Array CGH)

ARRAY CGH

The introduction of array-based comparative genomic hybridization (array CGH) marked a significant advancement in genome-wide analysis of chromosomal imbalances. This technique involves labeling patient and reference DNA with different fluorochromes (or dyes) and applying them in equal parts to a chip. The chip, a glass slide, contains thousands of DNA probes arranged in a high-density grid (array). The patient and reference DNA compete to bind to these probes based on their relative quantities. Using laser scanners and computer processing to detect the color or fluorescence signals, this method identifies genomic regions in the patient DNA that are either deleted (present in reduced amounts) or duplicated (present in increased amounts) compared to the reference DNA. The resolution of array CGH can range from 100 kb to less than 10 kb, depending on the number of DNA probes used, whereas traditional chromosome analysis has a maximum resolution of about 5 Mb.

Besides offering high-resolution genome-wide analysis, array CGH also allows for customized formats with very high-resolution, chromosome-specific arrays, or custom-designed arrays tailored to specific chromosome regions as defined by the researcher. However, a limitation of array CGH, when compared to conventional chromosome analysis, is that it cannot detect balanced chromosomal changes, such as translocations, or low-grade mosaicism.

For more information on the CGH+SNP array technique, please visit our page on molecular karyotyping.

Indications for CMA:

Postnatal

Patients with developmental delay, neurological abnormalities and signs of dysmorphia with unremarkable chromosome analysis

Patients with changes that appear balanced under light microscopy

Patients with a known imbalance that needs to be characterized more precisely

Patients with a marker chromosome

Prenatal

Clarification of a non-inherited chromosomal alteration

Sonographic abnormality with a normal chromosome

Literature

Kleemann et al. 2009, Prenat Diagn 29:1213 / Heinrich et al. 2009, J Lab Med 33(5):255 / Hochstenbach et al. 2009, Eur J Med Genet 52:161 / Menten et al. 2006, J Med Genet 43:625

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