What Is a CGH Array Genetic Test?

An array CGH, or comparative genomic hybridization array, is a genetic test that examines a person’s DNA for specific types of changes. It is designed to detect gains or losses in genetic material, known as copy number variants (CNVs). This technology provides a high-resolution view of the chromosomes, allowing for the identification of very small missing or extra pieces of DNA not visible with standard methods. The test is employed to investigate the underlying cause of various unexplained health and developmental conditions.

The CGH Array Process

The process begins with collecting a DNA sample, usually from a blood draw. For prenatal testing, samples can be acquired from amniotic fluid or chorionic villus sampling (CVS). The test works by comparing the patient’s DNA to a known “normal” or reference DNA sample.

For the comparison, both DNA samples are labeled with different colored fluorescent dyes. The labeled samples are combined and applied to a microarray chip that contains thousands of DNA probes. The patient and reference DNA then compete to bind, or hybridize, to these probes on the chip.

A computer scanner measures the intensity of the fluorescent signals from each probe. If the patient’s DNA color is more intense in a specific area, it signals an excess of genetic material, known as a duplication. If the reference DNA’s color is brighter, it indicates the patient has a missing segment of DNA, or a deletion.

Applications in Medical Diagnosis

In postnatal diagnosis, the CGH array is used for individuals with unexplained conditions, such as developmental delays, intellectual disabilities, or features of autism spectrum disorder. It can identify underlying chromosomal microdeletions or microduplications responsible for these conditions. The test is also used to investigate cases involving seizures or multiple congenital anomalies, which are physical differences present from birth.

In prenatal care, this genetic test provides more detailed information than a conventional karyotype. It is used as a follow-up when a prenatal ultrasound reveals structural abnormalities or growth issues in the fetus. If other screening tests suggest an elevated chance of a chromosomal condition, a CGH array may be performed to get a clearer picture, increasing the detection rate of chromosomal changes.

The array’s resolution is higher than that of traditional chromosome analysis. While older methods might detect changes on the scale of 5 to 10 megabases (Mb), a CGH array can identify imbalances as small as 50 to 100 kilobases (kb). This precision allows it to uncover genetic alterations in cases that would otherwise remain unresolved.

Interpreting Test Results

Results are categorized into three main possibilities. A “normal” or “negative” result indicates the test did not detect any extra or missing DNA of known clinical significance. It can also mean a detected copy number variant is a common, harmless variation.

An “abnormal” or “pathogenic” result means the array identified a deletion or duplication associated with specific health or developmental conditions. For instance, the test might detect a microdeletion known to cause a recognized genetic syndrome. This provides a diagnosis and helps guide medical management.

The third outcome is a “variant of uncertain significance” (VUS). This means a CNV was found, but there is not enough scientific evidence to determine if it is the cause of the patient’s condition or a benign variation. A VUS can create uncertainty and may require further steps, like testing parents to see if the variant was inherited, and involves detailed discussion with a genetic counselor.

Limitations of the Test

The CGH array has limitations and cannot detect every type of genetic mutation. A normal result does not rule out a genetic cause for a person’s condition; it only confirms no significant deletions or duplications were found. The test is not designed to identify small “spelling errors” in a single gene (point mutations), which are responsible for conditions like cystic fibrosis.

The array is also unable to detect large-scale chromosomal rearrangements that do not result in a net gain or loss of genetic material. These are called balanced rearrangements, such as translocations or inversions. Because no DNA is missing or extra, the fluorescent signals remain balanced, and the change goes undetected by this method.

Other genetic phenomena are also beyond the scope of a CGH array. It cannot identify uniparental disomy (UPD), where an individual inherits two copies of a chromosome from one parent and none from the other. It also may not detect low levels of mosaicism, a situation where a person has a mixture of genetically different cells. Investigating these possibilities requires different genetic tests, such as whole exome sequencing.