Recent advances in genomics have dramatically increased our capacity to analyze both normal and cancerous cell types by revealing a multitude of changes in genomic DNA, such as mutations and copy number alterations.
Array comparative genomic hybridization (aCGH) has become a valuable, genome-wide screening tool for the detection of chromosomal aberrations in the form of copy number imbalances in the field of cytogenetics. aCGH is a molecular technique based on the co-hybridization of sample and control genomic DNAs. The technique is relatively simple involving fluorescent labeling of sample DNA followed by co-hybridizing with normal control DNA spotted onto a glass slide or a chip. The major advantage of aCGH is that it offers improved resolution compared to traditional techniques and is more robust than mRNA expression arrays. Recent studies demonstrated the ability of aCGH to detect submicroscopic chromosomal imbalances in the range of a few megabases in 10–15% of patients with mental retardation and multiple congenital defects. Consequently, an increasing number of genetic facilities have implemented this technique for prenatal diagnosis. Since a simple DNA sample is required, much of the laborious steps in traditional karyotyping and cell culture can be circumvented.
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Dr. Mosca-Boidron and colleagues from Hôpital Le Bocage in Dijon (France) demonstrated the power of aCGH technique in a recent research article published in PLoS One. They developed a new and reproducible DNA extraction protocol allowing the isolation of 28.3ng to 238.7 ng of high-quality genomic DNA per milliliter of uncultured amniotic fluid of less than 16 weeks, quantities significantly greater than with already established protocols. Using aCGH with Enzo’s CGH labeling kit for oligo arrays on ten samples of less than 16 weeks, they detected and characterized three aneuploidy and two structural abnormalities. Interestingly, aCGH identified the duplication of a DNA segment that was previously missed by conventional prenatal karyotyping. Finally, known chromosomal imbalances were all successfully revealed by aCGH in twelve samples of more than 16 weeks thereby validating this newly developed protocol as a diagnostic tool. Currently, the international consensus is that prenatal diagnosis should be performed by aCGH as a first-line test in place of traditional karyotype analysis. Until aCGH is accepted as the standard technique for prenatal diagnosis, it should complement the existing standard prenatal karyotyping even when gestational age is less than 16 weeks, especially in cases with abnormal ultrasound findings.