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| The need to screen the whole genome at a resolution that surpassed the existing technologies led to the implementation of microarray based CGH. The principle is very similar to that employed for traditional CGH, where two differentially labeled specimens are cohybridized in the presence of Cot1 DNA; however, instead of metaphase spreads, the hybridization targets are DNA substrates immobilized on a glass slide.5-7 Subsequently, the arrays are scanned and the resultant data are analyzed by software that computes the log 2 ratios for a variety of copy number differences between a patient and reference sample (Fig. 4) Consequently, array-CGH is an entirely molecular technique with a cytogenetic application and represents a hybrid method that requires the expertise of both specialties. The current limitations of the technology include the inability to detect [balanced chromosome rearrangements and the equivocal nature of copy number alterations of unknown significance that may be identified.]
5 Trask BJ: Fluorescence in situ hybridization: applications in cytogenetics and gene mapping. Trends Genet 1991; 7: 149-154. 6 Pinkel D, Segraves R, Sudar D et al: High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 1998; 20: 207-211. 7 Cai WW, Mao JH, Chow CW, Damani S, Balmain A, Bradley A: Genome-wide detection of chromosomal imbalances in tumors using BAC microarrays. Nat Biotechnol 2002; 20: 393-396. |
The need to screen the whole genome at a resolution that surpassed the existing technologies led to the implementation of microarray-based CGH. The principle is very similar to that employed for traditional CGH, where two differentially labeled specimens are cohybridized in the presence of Cot1 DNA; however, instead of metaphase spreads, the hybridization targets are DNA substrates are immobilized on a glass slide.11–13 Subsequently, the arrays are scanned and the resultant data are analyzed by software that computes the log 2 ratios for a variety of copy number differences between a patient and reference sample. Consequently, array CGH (aCGH) is an entirely molecular technique with a cytogenetic application and represents a hybrid method that requires the expertise of both specialties. The current limitations of the technology include the inability to detect balanced chromosome rearrangements and the equivocal nature of copy number alterations of unknown significance that may be identified.
11. Solinas-Toldo, S. et al. 1997. Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer 20: 399–407. 12. Pinkel,D. et al. 1998. High resolution analysis ofDNA copy number variation using comparative genomic hybridization to microarrays. Nat. Genet. 20: 207–211. 13. Cai, W.W. et al. 2002. Genome-wide detection of chromosomal imbalances in tumors using BAC microarrays. Nat. Biotechnol. 20: 393–396. |
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