Biological Implications of the DNA Structures Associated with Disease-Causing Triplet Repeats

Abstract

The discovery of expanding repeat tracts associated with human disease has revealed an unexpected characteristic of a simple DNA sequence in the context of the human genome. This instability and the propensity for massive expansion likely reflect a new mutational mechanism (or combination of processes) that is not a feature of simpler model genetic organisms. The molecular mechanisms responsible for the genetic instability observed in triplet-repeat–associated disorders likely involve the unique structural properties associated with simple triplet-repeat tracts. A greater understanding of both the triplet-repeat DNA structures and the molecular mechanisms responsible for spontaneous mutations will be required before we can understand which of the models discussed above are responsible for repeat instability leading to triplet-repeat–associated human diseases.