How Genetic Tests Work - Molecular (sequence, target, array), Biochemical & Cytogenetics
Understanding Genetic Testing
Genetic testing involves examining a person’s DNA, found in blood or other tissues, for some abnormality linked to a disease or condition. DNA is actually a chemical alphabet composed of four units that make up all of the genes, or genetic material, found inside our cells. Genes are important for the body’s normal development and functioning. Each gene is unique due to the order of the four DNA units (see DNA).
When a mistake happens affecting part or all of the gene, this can result in an abnormal function or change in the body, leading to disease. The mistake can be fairly large or very small, and different types of genetic tests are used to identify the specific gene abnormality (see Genes and Their Properties).
The most common type of genetic testing is Newborn Screening. Almost every baby born in the United States has a blood sample tested for abnormal or missing genes or proteins. Early detection can allow the doctor to prescribe drugs or to place the baby on a specific diet in order to prevent or reduce the severity of a disease. Another type of testing, known as carrier testing, can help determine the risk of parents passing on a mutation to their child. Predictive or predispositional genetic testing can determine the risk of a healthy person developing a disease in the future. Finally, genetic tests can be used to look for gene abnormalities in persons suspected of having a genetic disease based on symptoms or family history.
Genetic testing is not always 100 percent accurate. Even when a genetic test positively detects a mutation, the test usually cannot determine when or what symptoms of the disease may show, which symptoms will occur first, how severe the disease will be, or how the disease will progress over time. If a test is negative, an individual may still be at risk for a disease. Therefore, it is important to speak to a health professional such as a genetic counselor to help you understand the benefits and risks of genetic testing and to answer any questions you may have before and after testing.
Genetic counselors are health professionals trained in the areas of medical genetics and counseling. Genetic counselors are trained to help persons as they consider testing, when they receive the results, and in the weeks and months afterward.
When deciding whether or not to have a genetic test for you or your child, several issues should be considered. In addition to the medical issues, genetic testing also raises some social, ethical, and legal issues you should be aware of. Below is a list of some of the issues you should discuss with your physician or genetic counselor:
- What treatments are available for this genetic disease?
- What impact would the genetic test results have on my family?
- What happens if the results are uncertain or inconclusive?
- What are the risks for future pregnancies?
- What is the cost of the test and will my insurance cover it?
- Who will have access to the test results?
- What emotional support services are available?
- Do other family members have a right to know the test results?
- What is the risk of discrimination by my employer or insurer?
Uses of Genetic Testing
Genetic tests can be used for many different purposes.
- Newborn screening is the most widespread use of genetic testing [See Chapter 4 for more information about newborn screening]. Almost every newborn in the U.S. is screened for
several genetic diseases. Early detection of these diseases can lead to interventions to prevent the onset of symptoms or minimize disease severity.
- Carrier testing can be used to help couples to learn if they carry—and thus risk passing to their children—an allele for a recessive condition such as cystic fibrosis, sickle cell anemia, and Tay-Sachs disease. This type of testing is typically offered to individuals who have a family history of a genetic disorder and to people in ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couple’s risk of having a child with a genetic condition.
- Prenatal diagnostic testing is used to detect changes in a fetus’s genes or chromosomes. This type of testing is offered to couples with an increased risk of having a baby with a genetic or chromosomal disorder. A tissue sample for testing can be obtained through amniocentesis or chorionic villus sampling.
- Genetic tests may be used to confirm a diagnosis in a symptomatic individual or used to monitor prognosis of a disease or response to treatment.
- Predictive or predispositional genetic testing can identify individuals at risk of getting a disease prior to the onset of symptoms. These tests are particularly useful if an individual has a family history of a specific disease and an intervention is available to prevent the onset of disease or minimize disease severity. Predictive testing can identify mutations that increase a person’s risk of developing disorders with a genetic basis, such as certain types of cancer.
Types of Genetic Testing
Several different methods are currently used in genetic testing laboratories. The type of test will depend on the type of abnormality that is being measured. In general, three major types of genetic testing are available: cytogenetic, biochemical, and molecular testing.
Cytogenetics involves the examination of whole chromosomes for abnormalities. Chromosomes of a dividing human cell can be clearly analyzed under a microscope. White blood cells, specifically T lymphocytes, are the most readily accessible cells for cytogenetic analysis since they are easily collected from blood and are capable of rapid division in cell culture. Cells from other tissues such as bone marrow (for leukemia), amniotic fluid (prenatal diagnosis), and other tissue biopsies can also be cultured for cytogenetic analysis.
Following several days of cell culture, chromosomes are fixed, spread on microscope slides, and then stained. The staining methods for routine analysis allow each of the chromosomes to be individually identified. The distinct bands of each chromosome revealed by staining allow for analysis of chromosome structure.
The enormous numbers of biochemical reactions that routinely occur in cells require different types of proteins. Several classes of proteins exist to fulfill multiple functions, such as enzymes, transporters, structural proteins, regulatory proteins, receptors, and hormones. A mutation in any type of protein can result in disease if the mutation results in failure of the protein to correctly function.
Clinical testing for a biochemical disease utilizes techniques that examine the protein instead of the gene. Tests can be developed to directly measure protein activity (enzymes), level of metabolites (indirect measurement of protein activity), and the size or quantity of protein (structural proteins). These tests require a tissue sample in which the protein is present, typically blood, urine, amniotic fluid, or cerebrospinal fluid. Because proteins are more unstable than DNA and can degrade quickly, the sample must be collected, stored properly, and shipped promptly according to the laboratory’s specifications.
For small DNA mutations, direct DNA testing may be the most effective method, particularly if the function of the protein is not known and a biochemical test cannot be developed. A DNA test can be performed on any tissue sample and requires very small amounts of sample. Some genetic diseases can be caused by many different mutations, making molecular testing challenging. For example, more than 1,000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause cystic fibrosis (CF). It would be impractical to sequence the entire CFTR gene to identify the causative mutation since the gene is quite large. However, since the majority of CF cases are caused by approximately 30 mutations, this smaller group of mutations is first tested before more comprehensive testing is performed.
Limitations to Genetic Testing
While the physical risks associated with most forms of genetic testing are small, since some tests only require a blood sample or buccal smear (retrieved from the inside of the cheek), there are many psychological, social, and financial effects on a person’s life that should be taken into consideration.
Gelehrter TD, Collins FS, Ginsburg D. Principles of Medical Genetics. 2nd Edition. Baltimore: Williams & Wilkins, 1998.
Genetic Alliance. 2007. Understanding Genetics: A Guide for Patients and Health Care Professionals. http://www.geneticalliance.org/ws_display.asp?filter=understanding.genetics.download
Mahowald MB, McKusick VA, Scheuerle AS, Aspinwall TJ (eds). Genetics in the Clinic: Clinical, Ethical, and Social Implications for Primary Care. St. Louis: Mosby, Inc. 2001. Scriver CR, Beaudet AL, Sly WS, Valle D (eds.). The Molecular and Metabolic Basis of Inherited Disease. New York: McGraw-Hill, 2001.
Thompson MW, McInnes RR, Willard HF. Thompson & Thompson: Genetics in Medicine, 5th Edition. Philadelphia: W.B. Saunders Company, 1991.
AccessDNA.com - Genetic Testing Methods: http://AccessDNA.com/condition/Genetic_Testing_Methods/669
American College of Medical Genetics http://www.acmg.net
GeneTests(online directory of genetic testing laboratories and genetic testing reviews) http://www.genetests.org
Genetic Testing-Genetics Home Reference http://ghr.nlm.nih.gov/handbook/testing
Genetic Testing for Genetic Disorders: Weight Benefits and Risks http://www.mayoclinic.com/health/genetic-testing/FL00076
Genetic Testing. Wikipedia. http://en.wikipedia.org/wiki/Genetic_testing