What is a genetic test?

First, understanding DNA

Virtually all cells in the human body, with the exception of mature red blood cells, contain a molecule called DNA (deoxyribonucleic acid). DNA contains much of the information needed for cells to function, divide, and produce the proteins that build and regulate the different tissues and organs of the body.

DNA can be thought of as a vast set of biological instructions organized into units called genes. Each gene contains information that may be involved in producing a protein or regulating a cellular process. Genes do not work in isolation: they interact with one another, with other regions of DNA, and with environmental factors.

DNA is also the fundamental molecule of inheritance. Each person receives approximately half of their genetic material from their mother and half from their father. During the formation of the egg cell and the sperm cell, a natural process called genetic recombination takes place: genetic material is rearranged and combined, helping to create the unique genetic makeup of each individual.

What genetic variants are

In addition to this normal recombination, changes can occur in DNA. Some are inherited, while others arise spontaneously during the formation of reproductive cells or later in life.

These changes are known as genetic variants. Many variants are completely normal and contribute to the natural diversity between individuals. Others may alter the function of a gene and be associated with a disease or with an increased predisposition to develop one.

What a genetic test analyzes

To perform a genetic test, biological material must first be obtained from the patient. Blood is one of the most commonly used samples because white blood cells contain DNA that can be extracted and analyzed. Depending on the study, saliva, cells from the inside of the cheek, skin, muscle, bone marrow, tumor tissue, or other samples may also be used.

Once the genetic material has been obtained, the laboratory uses different technologies depending on the medical question being investigated. For this reason, there is no single type of genetic test.

Types of genetic tests

Chromosome studies

Some studies look for abnormalities in the chromosomes, the structures in which DNA is organized inside cells. Humans normally have 46 chromosomes arranged in 23 pairs. Some tests can detect whether an extra chromosome is present, whether one is missing, or whether large chromosomal segments have been altered.

DNA sequence studies

Another important group of tests directly analyzes the DNA sequence. The genetic sequence can be imagined as a very long chain made up of four chemical units represented by the letters A, C, G, and T. The order of these letters carries biological information, and changes in one or more of them can affect how a gene functions.

Depending on the clinical situation, a physician may request analysis of a single gene, a group of genes, or a much larger portion of the genetic material:

• Gene panels simultaneously analyze several genes associated with a specific group of conditions, such as cardiomyopathies, epilepsies, neuromuscular diseases, or hereditary cancers.
• The exome mainly analyzes the regions of genes that contain instructions for producing proteins. Although these regions represent only a small proportion of total DNA, they contain a substantial proportion of known disease-associated variants.
• Whole-genome sequencing examines a much larger proportion of DNA, including regions that are not directly part of genes.

Studies of gene function

There are also technologies that analyze not only the DNA sequence itself, but how genes are functioning. Transcriptomics, for example, studies RNA molecules produced from genes and can help determine which genes are active in particular tissues and how certain variants may affect their function.

What the results mean

A genetic result is not always simply "positive" or "negative":

• In some cases, a variant that is clearly known to cause a disease is identified, and the finding may make an important contribution to establishing a diagnosis.
• In other cases, no relevant alteration is identified. This does not necessarily mean that the condition has no genetic cause: the responsible change may lie in a region that the test does not adequately analyze, the disease-causing gene may not yet be known, or the technology used may not be able to detect it.
• Testing may also identify variants whose meaning is not yet fully established, known as Variants of Uncertain Significance (VUS). A VUS is a change in DNA for which the available scientific evidence is not sufficient to determine with enough certainty whether it is related to a disease or simply represents part of normal genetic variation.

An inconclusive result can be particularly challenging. A patient may have clinical features that strongly suggest a specific condition while the molecular study remains inconclusive. In these situations, it may be useful to review additional scientific evidence, as we explain in our guide on how to interpret genetic test results.

Other uses of genetic testing

Genetic tests can also have purposes other than diagnosis:

• Carrier testing: determines whether a person carries a genetic variant that could potentially be passed on to their children.
• Genetic predisposition: estimates an increased likelihood of developing certain diseases. Having a predisposition does not necessarily mean the disease will develop; other genetic, environmental, and lifestyle-related factors also influence risk.
• Pharmacogenetics or pharmacogenomics: examines how genetic variants may influence the effectiveness or adverse effects of particular treatments. In some conditions, especially when therapies target specific molecular alterations, genetic results may also contribute to therapeutic decision-making.

Why interpretation matters so much

A genetic report may be technically correct while still being very difficult for a person without specialized training to understand. Concepts such as heterozygosity, penetrance, deletion, duplication, or pathogenicity can be complex even for healthcare professionals who do not routinely work in genetics.

It is also essential to understand the limitations of the test. Each genetic test examines particular regions or types of genetic alterations and is designed to answer specific questions. No genetic test can detect every possible change in DNA, and an inconclusive result does not necessarily mean that the test was performed incorrectly.

Scientific knowledge also continues to evolve. New publications, databases, and analytical methods may provide information that was not available when a report was originally issued. For this reason, the process does not necessarily end when the laboratory delivers the result. Understanding what was analyzed, what was found, what those findings mean, and what remains uncertain can be just as important as performing the test itself.

A genetic test should never be interpreted in isolation. Its results need to be considered together with the patient's medical history, family history, symptoms, other examinations, and the assessment of the treating physician. And when a report raises more questions than answers, uncertainty is a normal response: we discuss this in our guide on fear and frustration after genetic test results. For findings that cannot yet be classified, see our guide to understanding VUS results.

Frequently asked questions