Genetic testing is commonly defined as the analysis of specific genes, their products or their function, in addition to any type of test on DNA, RNA or chromosomes, in order to identify or exclude mutations associated with genetic conditions.
Testing may also be used to define the variability that exists between one individual and another, to resolve medical/legal queries, assess individual sensitivity, susceptibility and resistance, and genetically-determined individual response to medication. Compared with other laboratory tests, genetic testing has some particular features, as the results don't just involve one person, but also members of the person's family.
Types of test available
- diagnostic tests: enable a diagnosis or confirmation of a suspected medical condition in the person concerned. May be carried out in the prenatal period, following a preliminary indication after neonatal screening, or during the course of the person's lifetime. Diagnostic genetic testing is used to diagnose or exclude specific genetic conditions in symptomatic individuals. There are hundreds of tests for diagnosing numerous hereditary disorders. Many of these seek out alterations in specific genes responsible for the condition, as in cases such as cystic fibrosis, sickle cell anaemia or Duchenne muscular dystrophy. Many hereditary conditions can be identified indirectly by measuring anomalies in the final products (proteins or metabolites) of genes that could be altered. An example is haemophilia, a blood clotting disorder where screening detects a decrease in some proteins that regulate blood clotting. Genetic testing also provides information that is useful for seeking the same mutation in the relatives of an affected individual.
- tests to identify healthy carriers: make it possible to identify common mutations through population screening (in the neonatal period also), or analyse family members at risk due to relatives affected by fairly rare genetic conditions. Tests to verify carrier status detect the presence of a genetic variant that could be transmitted to offspring, and lead to a disorder if this variant, or a similar one, is also present in a partner. This type of testing can be offered to couples planning to have a child and who are at risk due to a family history of autosomal recessive disorders, such as cystic fibrosis or thalassemia. A carrier of an autosomal recessive disorder is usually asymptomatic, or only has mild symptoms. However, if that person's children inherit two pairs of the mutated gene, one from each parent, it is possible for the condition to develop. In each pregnancy, parents who are both carriers of an autosomal recessive variant have a one in four chance of having a child who is affected, a one in two chance of having a child who is an asymptomatic carrier, and a one in four chance of having a healthy child who is not a carrier.
- preclinical or presymptomatic tests: make it possible to identify the gene responsible for genetic conditions whose symptoms are not present at birth but appear later, even at an advanced age. These tests are generally used to diagnose late-onset conditions, such as Huntington's disease and hereditary haemochromatosis, in people with a positive family history for the presence of these conditions. A genetic consultation is particularly complex, and often requires psychological support during the period that precedes and follows the actual test. If a doctor deems it appropriate for a patient to undergo genetic testing to check a diagnostic hypothesis concerning a late or adult-onset condition, the patient (or parents in the case of children) must be provided with the reason for the test, the associated benefits and risks, the limitations of the result and the implications for the patient and the patient's family, and informed consent must be obtained. As a result, the test must be offered as part of a comprehensive consultation that seeks the opinion of the person involved, rather than issuing instructions and using an authoritarian approach. Anyone undergoing this type of testing must be aware of the implications that a positive test result could have on current and future offspring, and other blood relatives.
- expanded newborn screening: not genetic testing exactly, but a public medical prevention programme carried out on all newborns to check for 40 hereditary conditions, by looking for metabolites or enzymatic activity in a few drops of blood taken from the baby's heel. If the result of the screening is positive, the baby may undergo further investigation to confirm what is suspected, also through diagnostic genetic testing. For further information consult our section on newborn screening.
- prenatal genetic tests: provide information on the possibility of the foetus having a genetic condition. These tests are often looking for the presence of aneuploidies, or higher/lower amounts of chromosomes. These tests should not be confused with newborn screening. Prenatal screening tests carried out on maternal blood are usually offered during the first and second trimester of pregnancy (see screening in the first and second trimester of pregnancy). Additionally, non-invasive tests carried out on cell-free foetal DNA may also be offered, which analyse genetic material released from the placenta which circulates in the maternal blood. This type of screening is non-invasive and makes it possible to identify genetic abnormalities from the tenth week of pregnancy onwards. As these are screening tests and not diagnostic tests, they require further investigation. A positive screening result must be confirmed with the direct analysis of material of foetal origin collected during amniocentesis or chorionic villus sampling. In the case of tests that may influence reproduction decisions, comprehensive information is essential, and an approach from the medical staff involved which is not authoritarian, to ensure the beliefs and values of the individual or couple are respected. Tests to identify healthy carriers cannot be carried out as prenatal tests. Furthermore, if only one of the parents in a couple is a healthy carrier of a recessive condition, this is not an indication to carry out a prenatal diagnosis for this condition.
- susceptibility tests: make it possible to identify genetic variants which in themselves do not cause a disorder, but entail an increased risk in its development, following exposure to facilitating environmental factors, or the presence of other triggering genetic factors. This category includes most multifactorial adult disorders, such as cancer and diabetes. Often the mutation in a gene that creates susceptibility only represents a risk factor, and shows a higher predisposition to a condition. Genetic test results can only predict an increase or reduction in risk. The identification of people who are not sufferers, but have a high genetic risk, could justify the adoption of prevention measures that vary depending on the disorder in question. In these cases, a genetic consultation and obtaining informed consent are extremely delicate and complex procedures. Genetic test results can only predict whether or not the risk of contracting a disease is high or low with respect to the general population. They cannot give a direct correlation between the presence of a mutation and the disorder, only a statistical probability of illness. Any preventative screening must not lead to 'biological determinism', whereby the effects of the environment or other genes not examined are ignored. Therefore the use of these tests must be accompanied by, satisfactory, comprehensive information on current knowledge, the limitations and potential effects of 'genetic forecasting'.
- Non-clinical applications, such as paternity tests and body identification through forensic genetics, come under the large family of genetic tests as they involve similar tools and procedures, but they should not be confused with the previous tests.