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.