Cytogenetics (Pronounced: sigh-toe-gen-et-icks): The role of genetics specifically linked to the structure and function of the chromosomes (1).

If your provider, family, or friends have mentioned ‘Cytogenetics’ you may have questions about what that means for you or your loved ones.  The following information is a quick breakdown of what Cytogenetic testing consists of and how the results can help support a diagnosis and treatment options.

There are three major categories of cytogenetics we will review:

• Karyotyping

• F.I.S.H.

• Chromosomal Microarray

Karyotyping

There’s a good chance that when you hear Cytogenetics, they’re referring to Karyotyping; this is where laboratory technologists look at cells and arrange them based on their distinctive banding patterns. There are two types of karyotype analyses: Cancer and Constitutional. Cytogenetic Technologists are trained to perform analyses for both types. Typically 20 cells are analyzed per case, but several things can lead to more or fewer cells being analyzed (1,2).

Cancer Analysis may involve looking for abnormal cells; this could mean missing or extra chromosomes, a piece of a chromosome attaching to another (translocation), and more. By analyzing, medical directors and physicians are able to identify the type of cancer, level of risk, and personalize treatment plans to each patient’s needs.

Constitutional Analysis looks for abnormalities present in all or several cells, which could identify mosaicism. Mosaicism occurs when one organism has different genetics in some of their cells than the rest. Sometimes these changes involve whole chromosomes, but they also look in detail at the bands to determine if there are deletions or duplications. The karyotype to the right shows how technologists organize the chromosomes with their pairs; this karyotype is of a person that has an extra copy of chromosome 21, also known as Trisomy 21, or Down Syndrome.

F.I.S.H. (Fluorescent In-Situ Hybridization):

FISH involves attaching probes to a specific sequence of DNA within the chromosome to analyze it. The probe is made of fluorescent dye and a complementary DNA sequence to ensure it attaches to the correct target. Technologists traditionally work in dimly lit conditions to be able to observe the fluorescent signals and analyze hundreds of cells per test.

By looking at so many cells, technologists hope to establish an approximation for how many cells are impacted. There are tons of probes available today; FISH probes can be used to detect translocations, deletions, and duplications in both constitutional and cancer cases (1, 3).

Chromosomal Microarray

With microarray, DNA is extracted from the sample, fluorescently labeled, and attached to an array along with a known reference sample that is labeled with another color. Each well in an array contains a different probe that attaches to both samples and is initially analyzed by a computer that reports the fluorescence levels (1, 4). The image below provides a simplified representation of the analysis results as they look at the ratio between the patient sample and the known reference. Please note that the image is a simplified representation focusing on a single chromosome; technologists will see more detailed data across every chromosome following testing.

Microarray can find deletions and duplications much smaller than can be seen by karyotyping and it is often used in constitutional studies with clinical indications of cardiovascular or developmental syndromes. It can be utilized during cancer studies, but since different variants in cancer cells can arise rapidly, the analysis can be extremely complex with many cells having dramatically different numbers of chromosomes than in their cancer-free cells. There are some limitations to microarrays, like the inability to identify balanced translocations or inversions, but when SNP testing is also included microarrays can detect triploidy, three copies of a chromosome, and uniparental disomy, when both or a part of both chromosomes in a pair are from only one parent (1,4).