Genetic testing is a laboratory investigation consisting of analysis of chromosomes, DNA (deoxyribonucleic acid), RNA (ribonucleic acid), gene products (proteins) and other analytes of a person. It can serve two purposes: clinical – detection or exclusion of alterations related to conditions of a genetic nature, observation of prognosis, formulation of therapeutic strategy and monitoring of response; and not clinical – forensic and ancestral analysis.
Genetic tests, depending on the purpose with which they are applied, include:
Diagnostic testing: it supports the diagnosis, confirmation or exclusion of a disease of genetic origin and can be applied in the preimplantation, prenatal and postnatal periods. The indications of preimplantation genetic testing for monogenic conditions and for chromosomal and structural abnormalities overlap with those of invasive prenatal diagnosis (amniocentesis, villocentesis and cordocentesis), aimed at the diagnosis of a specific serious genetically transmissible condition caused by nuclear or mitochondrial DNA variations. In the postnatal period, diagnostic genetic tests are applied to individuals who present with a clinical overview that could be related to a pathological condition caused by genetic alterations.
Presymptomatic testing: it is applied to healthy individuals who have a positive family history for a genetic condition with late onset and often autosomal dominant transmission. A presymptomatic genetic test may be performed, for example, on an individual who has a positive family history for Huntington’s Chorea.
Screening testing: it is applied, usually, to asymptomatic individuals and involve conditions that are known, treatable or controllable. An example of a screening test is the newborn screening test, which is required, for example in each state in the United States, of almost every newborn to detect or rule out the presence of certain genetic and metabolic alterations causative of certain conditions. This type of testing is important so that care and treatment, for conditions under investigation such as congenital hypothyroidism and phenylketonuria, can begin right away. In Italy, expanded newborn screening is used to search for the possible presence of 49 different pathological conditions, including, in addition to the two mentioned above, cystic fibrosis and other congenital defects of intermediate metabolism. Positive outcomes of screening tests should be followed by more extensive investigations.
Tests for the identification of healthy carriers: to date, their use is limited to individuals with a positive family history for an autosomal recessive genetic condition (particularly conditions with a frequency of 1:10,000 or less); female individuals with a positive family history for an X-linked recessive genetic condition, e.g., hemophilia; individuals who are part of an ethnic group at high risk for a specific genetic condition, e.g., thalassemia in Mediterranean populations. These tests provide information on reproductive risk.
Susceptibility or predictive testing: they can investigate genetically known resistances or predispositions toward common conditions such as susceptibility to type 2 diabetes
Pharmacogenetics testing: it analyzes genetic variontions related to an individual’s response to a specific drug, thus allowing better determination of drug choice and dosing, in terms of efficacy and risk of adverse events.
Phenotypic testing: it studies the influence of genotype on phenotype, e.g. the effect of certain polymorphisms on skin coloration.
Forensic testing: it is performed for legal purposes and are related to e.g. identification of an individual responsible for a crime scene, identification of individuals following catastrophic events such as Hurricane Katrina, tests of parentage or paternity.
Ancestral testing: it defines an individual’s relationship to an ancestor or population, determining ethno-genealogical origins.
Bibliography
1. Dallapiccola, B. & Novelli, G. (2022). Genetica Medica. Edizioni Scientifiche Falco.
2. https://sigu.net/wp-content/uploads/2020/11/2043-2017_08_09_Raccomandazioni-PGT2017-ApprovatoCDSIGU.pdf
3. https://www.osservatorioscreening.it/screening-neonatale/
4. https://www.ncbi.nlm.nih.gov/books/NBK115571/
5. https://www.genome.gov/genetics-glossary/Genetic-Testing
6. https://www.cdc.gov/genomics/gtesting/genetic_testing.htm
7. Neri, G. & Genuardi, M. (2014). Genetica umana e medica. Terza edizione. Edra Masson.
8. https://www.ncbi.nlm.nih.gov/books/NBK552478/#!po=0.769231
9. https://sigu.net/wp-content/uploads/2021/01/1935-STANDARD_SIGU_LABORATORI_GENETICA_ed2018.pdf
