Single-gene and Multi-gene Disorders

It is important to distinguish between testing for single-gene (Mendelian) and multi-gene (complex) disorders. In Mendelian disorders, a “defective” gene may confer a virtually 100 percent probability for the manifestation of the disorder (Huntington’s, for example) or a significant increase in probability (as is the case with the “breast cancer genes” BRCA1 and BRCA2).

Mendelian disorders (at least those that have been characterized to date) generally occur in relatively defined and often small populations, with a prevalence of only one in one-thousand—or fewer—of the total population; because of this, many of them are classified as “rare diseases.” Testing for Mendelian disorders occurs primarily within the traditional medical setting, and test results indicate a specific increase in probability—information that is clinically useful.

In contrast, complex disorders tend to be quite common, including the “big four”—Alzheimer’s, cancer, cardiovascular disease and diabetes—and in fact are sometimes referred to using the shorthand “common diseases.” Tests for complex disorders are commercially available primarily through direct-to-consumer genetic testing companies. The frequency with which many complex disorders occur, combined with the very human desire to know—and the wish thereby to “control”—one’s future, have increased demand for DTC genetic testing. Unlike genetic tests for Mendelian disorders, however, tests for complex disorders are merely predictive of an altered risk associated with developing a disease. However, with the current information on SNP associations, the absolute risks tend to be low and are not of significant utility to alter standard of care.

combined with significant reductions in the cost of genetic tests, have spawned a new business model in which companies market genetic tests and personalized genetic profiles directly to consumers.

The rapid growth and evolution of the direct-to-consumer (DTC) genetic testing, “defined as genetic tests and services that are advertised directly to consumers, that are purchased through consumer-initiated requests, and that provide test results directly to the consumer without the involvement of the consumer’s health care provider,” has increased the focus on a number of issues raised by genetic testing.5 These include scientific, clinical, and technical issues; economic and financial issues;


 Direct-to-Consumer Genetic Testing, Report of the Secretary’s Advisory Committee on Genetics, Health, and Society, April 2010.

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