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.