Array comparative genomic hybridization (Array CGH) is a method for identifying gains or losses in the chromosomal material by the comparison of patient DNA with a reference DNA.
An array is a glass slide onto which thousands of oligonucleotide probes are spotted. The oligonucleotides represent sections of DNA and are distributed throughout the genome with some areas (ie where there are important genes) having more densely packed probes to ensure better coverage in these areas.
Array CGH process© St George’s, University of London
The two DNAs are mixed together and hybridised to the array slide containing the thousands of oligonucleotide probes spaced across the genome. Computer software uses quality control checks to ensure optimal results.
The software identifies the genomic region of gain or loss and the genes present within this region. For instance, where there is too much of the patient DNA (ie there is a duplication) and the patient DNA is labelled red, the resultant “spot” will look more red and where there is a deletion there will be over-representation of the green-labelled reference genome and the spot will look more green.
The user can then undertake further analysis of the clinical significance of this finding.
Clinical Applications of Array CGH
Array CGH is used for genome-wide, high-resolution screening of genomic copy number variation (deletions and duplications).
Diagnostic laboratories have increasingly been using array CGH as the first line investigation for patients with intellectual disability, developmental delay, autism and congenital abnormalities. It is also being applied in the prenatal setting following the detection of ultrasound scanning abnormalities in the pregnancy.
Array CGH has largely superseded the previous technique of examining the chromosomes down a microscope (karyotyping). This is primarily because it interrogates the chromosomes at higher resolution, detecting loss (deletions) or gain (duplications) of all or part of a chromosome down to less than 100kb.
Array CGH is more sensitive than karyotyping, detecting an additional 10-15% of clinically significant abnormalities. However, array CGH cannot detect chromosome rearrangements such as balanced translocations, which still require karyotyping, and is unable to identify DNA sequence changes of an individual gene.
It may detect mosaicism, but will not reliably do so, especially if it is present at a low level.
© St George’s, University of London
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