Expansion of trinucleotide repeats

This review describes a novel type of genome instability, expansion of trin ucleotide repeats. Originally discovered in 1991 upon cloning the gene resp onsible for the fragile X syndrome, it has proved to be a general phenomeno n responsible for a growing number of human neurological disorders. Besides apparent medical importance, the discovery of trinucleotide repeat expansi on unraveled a fundamental problem of human genetics: a non-Mendelian type of inheritance called anticipation. Understanding the mechanisms of repeat expansion and the molecular pathways leading from these expansions to human diseases became a formidable task for modern biology and one of its specta cular achievements. Here we discuss the major breakthroughs in this field m ade during the last decade, with an emphasis on molecular models of repeat expansion.