Overview of the field

The chapter provides an insight into the current status of research in the molecular mechanisms of microsatellite repeat instability, and in the pathogenic mechanisms of human diseases resulting from the expansion of microsatellite repeats. As the list of human diseases in this category has grown longer in the past decade, a wider variety of repeat motifs, which came with highly variable lengths of repeat tracts in different genomic locations are observed. Studies of in vitro Escherichia coli and yeast models provided multiple molecular mechanisms of repeat instability. Data from human tissues and mouse models suggested that some of these mechanisms are particularly relevant to the expansion of specific repeats in human diseases. As for the pathogenic mechanism by which the repeat expansion leads to the disease, major models include a loss of function of the gene and a gain of function by the mutant RNA transcript or protein product. However, the pathogenic mechanism varies from one disease to another, depending on the motif, length, and intragenic location of the repeat. Understanding the molecular mechanisms of repeat instability and pathogenic mechanisms is not only of scientific interest but also essential for the development of rational treatment of these diseases.