Scientists looking for a disease gene typically have
begun by studying DNA samples from members of "disease families," in which
numerous relatives, over several generations, have developed the same
illness such as colon cancer. Researchers look for genetic markers -
easily identifiable segments of DNA - that are consistently inherited by
persons with the disease but are not found in relatives who are
disease-free. Then, they painstakingly narrow down the target DNA area,
pull out candidate genes, and look for specific mutations.
Before a specific gene is located, linked genetic markers can be used
to test members of the family under study. However, to test wider
populations, it is necessary to find the gene itself. Because the DNA
highway is so vast, this can be enormously difficult. In the case of
Huntington's disease, it took 10 years to advance from linkage markers to
the gene.
Once a disease gene has been cloned (copied to get enough to study in
detail) and identified, scientists can construct DNA
probes - lengths of single-stranded DNA that match parts of the known
gene. (This is possible because, in double-stranded DNA, adenine in one
strand always pairs with thymine in the other, and guanine pairs with
cytosine.) The single-stranded probe then seeks and binds to complementary
bases in the gene. When the probe has been tagged with a radioactive atom,
the area of DNA it binds to - the gene - lights up. The fact that some
diseases exhibit multiple mutations within the same gene adds to the
complexity of gene testing.
Functional gene tests, which detect protein rather than DNA, can
demonstrate not only that a mutated gene is present but also that it is
actively making an abnormal protein or no protein at all.
