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Array Comparative Genomic Hybridization in Pathology

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Part of the book series: Molecular Pathology Library ((MPLB,volume 1))

Abstract

Comparative genomic hybridization (CGH) is a molecular cytogenetic method for the detection and mapping of chromosomal gains and losses.1 It is based on the cohybridization of differentially labeled test and reference DNAs onto metaphase spreads, which usually have been prepared from peripheral blood lymphocytes of a healthy donor. The signal intensity ratios of the two labels along the chromosomes then reflect DNA copy number changes in the test genome relative to the reference genome. Although CGH has tremendously contributed to our knowledge of chromosomal aberrations, unfortunately its resolution is limited to about 3–10 Mb.2 Resolution of CGH has significantly improved when samples were not hybridized to metaphase spreads but to DNA targets that have been arrayed on a glass substrate. This modification of the original technique has been named array CGH 3 or matrix CGH.4 In theory, resolution of array CGH is only limited by number and quality of DNA targets arrayed on the slide. The principle of array CGH is illustrated in Figure 10.1.

Principle of array comparative genomic hybridization. Differentially labeled test and reference DNA (green and red spheres, respectively) are cohybridized onto an array of DNA spots printed on a glass slide. In the case of a deletion in the test DNA, fewer test DNA will bind to the corresponding spots and the red label of the reference DNA will prevail. Gains in the test genome can be identified by a dominance of the green label of the test DNA. Spots, representing sequences with the same copy number in the test genome relative to the reference genome, appear yellow. For bacterial artificial chromosome arrays, an excess of repetitive Cot DNA (blue spheres) has to be added in order to suppress otherwise nonspecifically binding repetitive sequences.

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Ullmann, R. (2008). Array Comparative Genomic Hybridization in Pathology. In: Zander, D.S., Popper, H.H., Jagirdar, J., Haque, A.K., Cagle, P.T., Barrios, R. (eds) Molecular Pathology of Lung Diseases. Molecular Pathology Library, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72430-0_10

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  • DOI: https://doi.org/10.1007/978-0-387-72430-0_10

  • Publisher Name: Springer, New York, NY

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