Chromosomal microarray analysis (CMA), also known as array comparative genomic hybridization (aCGH), is a molecular technique that relies on a competition between labeled patient and reference DNA for hybridization to an array of immobilized target sequences. CMA facilitates the simultaneous detection of thousands of target sequences and has become the gold standard for assessment of genomic imbalance. Microarray refers to a microchip-based testing platform that allows high-volume, automated analysis of many pieces of DNA at once. CMA chips use labels or probes that bond to specific chromosome regions. Computer analysis is used to compare a patient's genetic material to that of a reference sample.
Overview of the CMA method: Typically, a microarray is a small glass slide on which thousands of genes are arrayed. Using conventional DNA hybridization process, DNA probes are attached (hybridized) with differentially labelled DNA – patient (green) and control/reference (red) – to reveal copy number variants (CNV), or gains and losses, at a much higher resolution than routine chromosome analysis. In a normal situation, each probe on the array should hybridize equally to test (green) and control (red) DNA. This will produce a yellow signal. Extra pieces of DNA produce a green signal and missing pieces produce a red signal. The slide is scanned and images analyzed by computer.
(See the diagram image of the CMA method presented in the following page).
Fluorescently labeled target sequences that bind to a probe sequence generate a signal that depends on the hybridization conditions. Total strength of the signal depends upon the amount of target sample binding to the probes present on that spot.
Copy number variants (CNVs): CMA technology is commonly used to determine if there are small extra (micro-duplication) or missing (micro-deletion) pieces of genetic information. These gains and losses are called copy number variants (CNVs). A CNV can have no medical significance or consequence or it can be pathogenic, resulting in physical and/or intellectual consequences. CNVs can also be protective against certain diseases. The contribution of CNVs to common, complex diseases, such as diabetes, is less well understood.
Typically, different laboratories perform CMA using different technology platforms and with different array design and content.
CMA is increasingly being utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA).
