The mutant alleles in certain diseases, such as Huntington disease, fragile X syndrome, and myotonic dystrophy, differ from their normal counterparts only in the number of tandem copies of a trinucleotide. The expansion of the trinucleotide repeat in the mutant allele can be in a coding region (Huntington and spinobulbar muscular atrophy) or in an untranslated region of the gene (fragile X and myotonic dystrophy). In these diseases, the number of repeats often increases with successive generations and correlates with increasing severity and decreasing age of onset, a phenomenon called anticipation.
In the normal Huntington allele, there are five tandem repeats of CAG in the coding region. Affected family members may have 30 to 60 of these CAG repeats. The normal protein contains five adjacent glutamine residues, whereas the proteins encoded by the disease-associated alleles have 30 or more adjacent glutamines. The long glutamine tract makes the abnormal proteins extremely unstable.
Defective gene locus: 19q13
Repeat Size: from normal (CTG)5-35 to pathological (CAG)50+
Repeat occurs in 3'-untranslated region of a kinase gene (DMK)