Genetics and Health - Genetic Testing

A genetic test is the analysis of human DNA, ribonucleic acid (RNA), chromosomes, and proteins in order to detect heritable diseases for the purposes of diagnosis, treatment, and other clinical decision making. Most genetic testing is performed by drawing a blood sample and extracting DNA from white blood cells. There is a broad range of techniques that can be used for genetic testing. Genetic tests have diverse purposes, including screening for and diagnosis of genetic disease in newborns, children, and adults; the identification of future health risks; the prediction of drug responses; and the assessment of risks to future offspring.

There is a difference between genetic tests performed to screen for disease and testing conducted to establish a diagnosis. Diagnostic tests are intended to definitively determine whether a patient has a particular problem. Diagnostic tests are generally complex tests and commonly require sophisticated analysis and interpretation. They may be expensive and are generally performed only on persons believed to be "at risk," such as patients who already have symptoms of a specific disease.

In contrast, screening is performed on healthy, asymptomatic (showing no symptoms of disease) people and often to the entire relevant population. A good screening test is relatively inexpensive, easy to use and interpret, and assists to identify which individuals in the population are at higher risk for a specific disease. By definition, screening tests identify persons who need further testing or persons who should take special preventive measures or precautions. For example, persons deemed especially susceptible to genetic conditions with specific environmental triggers are advised to avoid the environmental factors linked to developing the disease.

Examples of genetic tests used to screen relevant populations include screening persons of Ashkenazi Jewish heritage (the east European Jewish population primarily from Germany, Poland, and Russia, as opposed to the Sephardic Jewish population primarily from Spain, parts of France, Italy, and North Africa) for Tay-Sachs disease, African-Americans for sickle cell disease, and expectant mothers over age thirty-five whose fetuses are at higher risk for Down syndrome. Table 4.1 lists a few of the more than one thousand DNA-based genetic tests that are currently available.

The most common form of genetic testing is screening of newborn infants for genetic abnormalities. In the

TABLE 4.1

Currently available DNA-based gene tests

Alpha-1-antitrypsin deficiency (AAT; emphysema and liver disease)

Amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease; progressive motor function loss leading to paralysis and death)

Alzheimer's disease (APOE; late-onset variety of senile dementia)

Ataxia telangiectasia (AT; progressive brain disorder resulting in loss of muscle control and cancers)

Gaucher disease (GD; enlarged liver and spleen, bone degeneration)

Inherited breast and ovarian cancer (BRCA 1 and 2; early-onset tumors of breasts and ovaries)

Hereditary nonpolyposis colon cancer (CA; early-onset tumors of colon and sometimes other organs)

Charcot-Marie-Tooth (CMT; loss of feeling in ends of limbs)

Congenital adrenal hyperplasia (CAH; hormone deficiency; ambiguous genitalia and male pseudohermaphroditism)

Cystic fibrosis (CF; disease of lung and pancreas resulting in thick mucous accumulations and chronic infections)

Duchenne muscular dystrophy/Becker muscular dystrophy (DMD; severe to mild muscle wasting, deterioration, weakness)

Dystonia (DYT; muscle rigidity, repetitive twisting movements)

Fanconi anemia, group C (FA; anemia, leukemia, skeletal deformities)

Factor V-Leiden (FVL; blood-clotting disorder)

Fragile X syndrome (FRAX; leading cause of inherited mental retardation)

Hemophilia A and B (HEMA and HEMB; bleeding disorders)

Hereditary hemochromatosis (HFE; excess iron storage disorder)

Huntington's disease (HD; usually midlife onset; progressive, lethal, degenerative neurological disease)

Myotonic dystrophy (MD; progressive muscle weakness; most common form of adult muscular dystrophy)

Neurofibromatosis type 1 (NF1; multiple benign nervous system tumors that can be disfiguring; cancers)

Phenylketonuria (PKU; progressive mental retardation due to missing enzyme; correctable by diet)

Adult polycystic kidney disease (APKD; kidney failure and liver disease)

PraderWilli/Angelman syndromes (PW/A; decreased motor skills, cognitive impairment, early death)

Sickle cell disease (SS; blood cell disorder; chronic pain and infections)

Spinocerebellarataxia, type 1 (SCA1; involuntary muscle movements, reflex disorders, explosive speech)

Spinal muscular atrophy (SMA; severe, usually lethal progressive muscle-wasting disorder in children)

Thalassemias (THAL; anemias—reduced red blood cell levels)

Tay-Sachs disease (TS; fatal neurological disease of early childhood; seizures, paralysis)

SOURCE: "Some Currently Available DNA-Based Gene Tests," in "Gene Testing," U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research, Human Genome Program, Human Genome Project Information, http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetest.shtml (accessed December 29, 2005)

United States, according to a 2003 report by the Government Accountability Office, about four million newborns per year are screened by testing blood obtained from a prick of the newborn's heel within the first few days of life. Specific genetic disorders such as phenylketonuria (PKU), an inherited error of metabolism resulting from a deficiency of an enzyme called phenylalanine hydroxylase, can be identified with heel-prick testing. The lack of this enzyme can produce mental retardation, organ damage, and postural problems. Children born with PKU must pay close attention to their diets so that they may lead healthy, normal lives.