Health Problems, Small Genetic Differences

When you get right down to it—and by "right down to it," I mean at the DNA level—we are far more like one another than most of us would care to admit. It is estimated that we are 99 percent genetically identical, with that varying 1 percent causing quite a lot of variance. (The 1 percent explains, for instance, why I'm writing this column instead of sprinting in the Olympics or starring as the next James Bond.) An ever-growing body of research is also demonstrating how some of these differences put us at risk for a variety of diseases, including cancer, Alzheimer’s, and disorders that affect the immune system. Many of these differences are as small as one can imagine: a single change in the order of our DNA.
As I learned in college, and children now learn in elementary school, DNA is made up of four letters, or nucleotides: adenosine (A), guanine (G), cytosine (C), and thymidine (T). At certain points in our genes, we have variations in these letters, called polymorphisms. For example, where one part of the population may have a C, the rest of the population will have a T. These single nucleotide polymorphisms are known in the field as SNPs (pronounced "snips").







In a recent paper in the New England Journal of Medicine, a group of investigators looked at SNPs from over 2,500 patients with two rheumatologic disorders—lupus and rheumatoid arthritis—and compared their DNA with that of over 2,000 normal patients. The scientists concentrated their efforts on 13 different genes on a part of chromosome 2 that had previously been identified as containing genes related to these disorders. Patients with a particular SNP in a gene called STAT4 were 32 percent more likely to have rheumatoid arthritis and 55 percent more likely to have lupus. If you had two copies of this particular SNP (one from each of your parents), then your risk for either disorder was even higher.