Gene tests (also called DNA-based tests), the newest and most sophisticated of the techniques used to test for genetic disorders, involve direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic examination of stained or fluorescent chromosomes. Genetic tests are used for several reasons, including:

• Carrier screening, which involves identifying unaffected individuals who carry one copy of a gene for a disease that requires two copies for the disease to be expressed

• Preimplantation genetic diagnosis

• Prenatal diagnostic testing

• Newborn screening

• Presymptomatic testing for predicting adult-onset disorders such as Huntington's disease

• Presymptomatic testing for estimating the risk of developing adult-onset cancers and Alzheimer's disease

• Confirmational diagnosis of a symptomatic individual

• Forensic/identity testing

Preimplantation genetic diagnosis (PGD) is a test that screens for genetic flaws among embryos used in in-vitro fertilization. With PGD, DNA samples from embryos created in-vitro by the combination of a mother's egg and a father's sperm are analyzed for gene abnormalities that can cause disorders. Fertility specialists can use the results of this analysis to select only mutation-free embryos for implantation into the mother's uterus.

Before PGD, couples at higher risks for conceiving a child with a particular disorder would have to initiate the pregnancy and then undergo chorionic villus sampling in the first trimester or amniocentesis in the second trimester to test the fetus for the presence of disease. If the fetus tested positive for the disorder, the couple would be faced with the dilemma of whether or not to terminate the pregnancy. With PGD, couples are much more likely to have healthy babies. Although PGD has been practiced for years, only a few specialized centers worldwide offer this procedure.

In gene tests, scientists scan a patient's DNA sample for mutated sequences. A DNA sample can be obtained from any tissue, including blood. For some types of gene tests, researchers design short pieces of DNA called probes, whose sequences are complementary to the mutated sequences. These probes will seek their complement among the 3 billion base pairs of an individual's genome. If the mutated sequence is present in the patient's genome, the probe will bind to it and flag the mutation. Another type of DNA testing involves comparing the sequence of DNA bases in a patient's gene to a normal version of the gene. Cost of testing can range from hundreds to thousands of dollars, depending on the sizes of the genes and the numbers of mutations tested.

What Are Some of the Pros and Cons of Gene Testing?

Gene testing already has dramatically improved lives. Some tests are used to clarify a diagnosis and direct a physician toward appropriate treatments, while others allow families to avoid having children with devastating diseases or identify people at high risk for conditions that may be preventable. Aggressive monitoring for and removal of colon growths in those inheriting a gene for familial adenomatous polyposis, for example, has saved many lives. On the horizon is a gene test that will provide doctors with a simple diagnostic test for a common iron-storage disease, transforming it from a usually fatal condition to a treatable one.

Commercialized gene tests for adult-onset disorders such as Alzheimer's disease and some cancers are the subject of most of the debate over gene testing. These tests are targeted to healthy (presymptomatic) people who are identified as being at high risk because of a strong family medical history for the disorder. The tests give only a probability for developing the disorder. One of the most serious limitations of these susceptibility tests is the difficulty in interpreting a positive result because some people who carry a disease-associated mutation never develop the disease. Scientists believe that these mutations may work together with other, unknown mutations or with environmental factors to cause disease.

A limitation of all medical testing is the possibility for laboratory errors. These might be due to sample misidentification, contamination of the chemicals used for testing, or other factors.

Many in the medical establishment feel that uncertainties surrounding test interpretation, the current lack of available medical options for these diseases, the tests' potential for provoking anxiety, and risks for discrimination and social stigmatization could outweigh the benefits of testing.

For What Diseases Are Gene Tests Available?

Currently, more than 900 genetic tests are available from testing laboratories. Some gene tests available in the past few years from clinical genetics laboratories appear below. Test names and a description of the diseases or symptoms are in parentheses. Susceptibility tests, noted by an asterisk, provide only an estimated risk for developing the disorder.

Some 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)
• Prader Willi/Angelman syndromes (PW/A; decreased motor skills, cognitive impairment, early death)
• Sickle cell disease (SS; blood cell disorder; chronic pain and infections)
• Spinocerebellar ataxia, 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)

Currently in the United States, no regulations are in place for evaluating the accuracy and reliability of genetic testing. Most genetic tests developed by laboratories are categorized as services, which the U.S. Food and Drug Administration does not regulate. Only a few states have established some regulatory guidelines. This lack of government oversight is particularly troublesome in light of the fact that a handful of companies have started marketing test kits directly to the public. Some of these companies make dubious claims about how the kits not only test for disease but also serve as tools for customizing medicine, vitamins and foods to each individual's genetic makeup. Another fear is that individuals who purchase such kits will not seek out genetic counseling to help them interpret results and make the best possible decisions regarding their personal welfare.

Does Insurance Cover Genetic Testing?

In most cases, an individual will have to contact his or her insurance provider to see if genetic tests, which cost between $200 and $3,000, are covered. Usually insurance companies do not cover genetic tests, those that do will have access to the results. Insured persons would need to decide whether they would want the insurance company to have this information. States have a patchwork of genetic-information nondiscrimination laws, none of them comprehensive. Existing state laws differ in coverage, protections afforded and enforcement schemes. The National Conference of State Legislatures provides a listing of current legislation regarding genetic information and health insurance. The recent marketing of genetic test kits directly to consumers, may lead to an increase in demand for insurance coverage.

Sources: Office of Biological and Environmental Research, Department of Energy,

Updated: August 29, 2006

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