Microarray Test: What You Need to Know before Ordering Chromosomal Microarray

So, your doctor or genetic counselor has advised you to have a chromosomal microarray test done. Chromosomal microarray is a mouthful and you are probably wondering what it actually is and perhaps even whether it hurts or not.

We have all heard that famous “it’s all in your genes” statement, implying that most of who we are is found within our genes and DNA. Taking this statement further, our genes are found on chromosomes, and we can find out a lot about what illnesses we have or might have based on the analysis of our chromosomes, also called karyotyping. So that is the “chromosomal” part of the chromosomal microarray mouthful. What about microarray? Taken literally, ‘micro’ means very small, while ‘array’ simply means an ordered series or arrangement. Taken together and placed in the context of biology, microarray is essentially a very small arrangement of genetic material on a chip.

Perhaps you are now even more confused, wondering how all of that information fits into your story of needing a chromosomal microarray. Let’s back up a little and bring it all back together a few sentences later.

For several reasons, it is of utmost importance to figure out what is beneath an individual’s intellectual challenges and/or congenital anomalies. These reasons include counseling (perhaps you are in the middle of family planning and need prenatal testing in order to know your prognosis), or you need access to appropriate resources or you simply need to put your mind at ease with knowing what lies ahead. A chromosomal microarray, being a high-resolution genetic test, looks at very small gains and losses of genetic material within the genomic information of an individual. It can help figure out things such as isolated spectrum disorder as well as other findings, isolated developmental delay or intellectual disability, several congenital abnormalities when there is no syndrome diagnosis as well as unusual physical features. Given all this, that still begs the question of what a chromosomal microarray really is.

Fundamentally, the chromosomal microarray technology is used to figure out if there are any abnormalities within an individual’s pool of genes. These abnormalities, or mutations, often manifest themselves as either small extra or missing pieces of genetic information. In the laboratory, these gains and losses are called copy number variants (CNVs). These have varying effects on individuals. They can either be of no consequence at all, they can result in physical and/or intellectual consequences or they can be protective against a disease as in the case of HIV.

At the heart of the microarray technology is a small glass slide that houses thousands of genes in an array, or in an ordered fashion (see definition above). That glass slide is then washed with DNA probes that are labeled with either green or red probes. The patient’s DNA is labeled with green probes while the control/reference probes are red. Two colors are used to visualize the CNVs (gains and losses) in a much higher resolution. In a normal (or healthy) scenario, each probe should attach (or hybridize) to the test (green) as well as control (red) DNA, which will result in a yellow signal. Therefore, if there are any extra pieces of DNA, implying extra genetic material or an abnormality, that will produce a green signal. Similarly, missing DNA (or the lack of genetic material) will produce a red signal on the readout. Each glass slide is scanned and image analyzed via computer.

How is the test done?

How is the test done

First of all, it is important to know that there are four types of testing programs. These include newborn screening, carrier testing, prenatal testing (genetic test) and presymptomatic (predictive) testing.

The chromosomal microarray is done very similarly to all other genetic tests. All that is needed is a patient’s DNA, which can be extracted from materials such as saliva or blood. Either the patient’s doctor or the patient themselves (following a referral) order a test kit from any company that offers chromosomal microarray analysis testing. Once the kit arrives, patients can either submit their sampling materials themselves or have their blood drawn at their doctor’s office. Once the respective laboratories receive the patient’s materials, DNA is extracted and then hybridized to the microchips of DNA (see above.).

What do the results mean?

An ordering physician, as well as a genetic counselor, are trained to discuss the results of a chromosomal microarray test, which is why it is important to consult with them prior to making specific conclusions. In a normal scenario, micro-deletions/micro-duplications are excluded. However, this does not rule out a disorder that is caused by a mutation within a single gene. It is recommended that further genetic consultations should be done in order to find out if more genetic testing should be done.

If a pathogenic micro-deletion or micro-duplication is found after a chromosomal microarray, it can be identified based on the previously described disorder. Also, depending on what has been found, it may warrant further parental testing and/or additional medical testing.

Lastly, if a variation has been found that has an unclear clinical significance, it is important to know that now every CNV in the genome leads to disease. In this situation, it is important to have parental samples and information in order to conduct additional genetic testing and find out if, at least, the CNV is familial and, therefore, less likely to be pathogenic.

Chromosomal microarrays are also offered to pregnant women following an irregular ultrasound that may point to a genetic abnormality of the fetus. In that situation, the baby’s DNA is analyzed to look for possible genetic reasons behind the ultrasound indications. Typically, a prenatal test requires a sampling of the amniotic fluid while only a buccal swab is needed for a postnatal test. Following submission of the specimen or material, laboratory procedures are pretty much the same as described above.

Laura Day