Repeating DNA surprises once again.

In 1991, geneticists discovered a new type of DNA mutation. A small stretch of the genetic material had mysteriously copied itself over and over, disrupting the function of a crucial gene and causing a form of mental retardation called fragile X syndrome. Other diseases, including Huntington's, result from similar mutations in different genes, researchers quickly found. Since the proliferating genetic bits are trios of nucleotides, the fundamental building blocks of DNA, investigators call these disorders triplet repeat diseases. There are four kinds of DNA nucleotides-A, C, G, and T-and only CAGs and CCGs seemed to repeat inappropriately. Now, investigators have found that GAA can also copy itself unpredictably.

A large number of GAA repeats, anywhere between 200 and 900, in a gene on chromosome 9 causes the progressive disorder Friedreich's ataxia, report Massimo Pandolfo of Baylor College of Medicine in Houston and his colleagues in the March 8 Science. This disease, which slowly degrades the spinal cord, heart, pancreas, and other organs, occurs only when the gene's two copies-the one inherited from the mother and the one from the father-are both flooded with GAA repeats.

The ability of GAA to repeat offers a challenge to investigators trying to explain the generation of the triplet repeat diseases, observes Stephen T. Warren of Emory University School of Medicine in Atlanta. Based on test-tube experiments with DNA, researchers had proposed that repeated spans of CAG and CGG triplets form unique DNA structures, such as those called hairpins, that are prone to replicate out of control. "The GAA repeat doesn't form these structures," says Warren.

Huntington's and other triplet repeat diseases strike at younger ages and more severely in subsequent generations as the number of CAG or CCG repeats increases. Scientists refer to this tendency as anticipation. Friedreich's ataxia, however, shows that anticipation does not occur in every disease caused by triplet repeats. Though the number of GAA repeats tends to increase with each generation, Friedreich's almost always strikes in adolescence and does not become more destructive. This disorder suggests that triplet repeats may also cause other diseases that don't demonstrate anticipation. "Now one can consider a lot of other disorders as candidates for this type of mutation," says Warren.