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Genetic Testing

The use of genetic information to predict future onset of disease in an asymptomatic (presymptomatic) person is called predictive genetic testing.

Every aspect of our being is influenced by both genes and environment. In the future, a strategy for influencing development may be to alter genes. At present, the environment in which genes act can sometimes be changed, and thereby moderate their impact (taking medications or avoiding specific hazards, for example). Sometimes there is no known way to change the deterministic power of a gene, though with increased knowledge of its workings there is always hope for future interventions. Whether or not the course of a disease can be altered, predictive information is increasingly available, and some people choose knowledge over uncertainty.

For generations, people have used family information to anticipate outcomes for themselves. Insurers consider parental age and cause of death for actuarial tables. Evolution in knowledge has been from information with considerable associated uncertainty to that with greater predictive capacity. Huntington Disease (HD) became the prototype for predictive testing and serves to illustrate.

HD is a neurological disease with onset of symptoms usually during adulthood. It is inherited as an autosomal dominant trait; someone with an affected parent has a 50/50 chance of eventually developing the disease. The HD gene was the first human gene to be linked to an otherwise anonymous DNA marker (a restriction fragment length polymorphism, called G8), and long before the gene itself was identified, this marker and others like it became powerful predictive tools. Families in which HD was segregating were studied to determine which variant of the marker was tracking with the mutant HD gene; once that relationship was established, the marker(s) could be used to test family members who wished to know their genetic status. This indirect approach to testing was associated with some probability of error, since the markers were only close to the gene, not within it. With discovery in 1993 of the gene responsible for HD, a direct assay was immediately possible, with or without access to samples from other family members, and results became highly predictive.

The laboratory advances made access to this information possible, but it was quickly recognized that great care would be needed in the application of such knowledge to individuals at risk. A large Canadian collaborative study of predictive testing for HD, initiated in the late 1980s, has been particularly informative for assessing the impact of such information on individuals and families and developing guidelines for the practice of predictive medicine, including the need for supportive counseling and follow-up. Lessons from experience with this relatively obscure disorder were soon applied to other late-onset diseases for which predisposing mutations were identified. Notable in this context are inherited cancers such as familial breast cancer or colon cancer, other neurological disorders such as spino-cerebellar ataxias (including Machado-Joseph Disease), and familial Alzheimer disease. Common afflictions such as heart disease, diabetes, and arthritis will eventually be amenable to similar investigations.

The Human Genome Project recognized the need for ethical considerations to match scientific advances, and its mandate includes significant support for research into ethical, legal and social issues. This has set new standards for the application of knowledge, respecting public concerns about the implications of new technologies. The opportunity to know ones genetic destiny has potential risks that must be mitigated in order for the benefits to be realized. Once the predictive test for HD was available, it was soon apparent that not everyone at risk wished to be tested. The right not to know is a significant issue. The genetic nature of these diseases adds complication, becasue information revealed about one individual may secondarily imply information about other family members, and individual choices will impact others in the family network. Acting upon respect for individual autonomy, early guidelines have advised against the testing of children for late-onset disorders in the absence of preventive options. In countries without universal health care, insurance implications of predictive testing are huge. Will people be required to submit a clean genetic bill of health in order to secure health or life insurance?

Eventually, there will be effective therapeutic interventions for diseases such as HD and Alzheimer disease, individually tailored to the needs of those at risk. Until then, there will be controversy over the practice of predictive testing, but many will continue to choose knowledge and maintain hope for the future.



Nussbaum, R.L., Roderick R. McInnes, Huntington F. Willard Genetics in Medicine. Philadelphia: Saunders, 2001.

Rimoin, D.L. Emery and Rimoin's Principles and Practice of Medical Genetics. London; New York: Churchill Livingstone, 2002.

Strachan, T., and A. Read. Human Molecular Genetics. New York: Bios Scientific Publishers, 1998.


Leparc. G.F. "Nucleic Acid Testing for Screening Donor Blood." Infectious Medicine, no. 17 (May 2000): 310–333.A.

Selwa, R. "Researcher Talks About Ethics of Genetic Therapy" Macomb Daily (2000):1A, 8A.


National Human Genome Research Institute. "Ethical, Legal and Social Implications of Human Genetic Research." October 2002 [cited February 2, 2003]. <http://www.nhgri.nih.gov/ELSI/>.

Janet A. Buchanan

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