Triplet Repeat Expansions

Triplet repeat expansion refers to an increase in trinucleotide repeats. Trinucleotide repeats are considered a subset of simple sequence repeats (aka short tandem repeats or microsatellites). In humans, triplet repeat expansion appears to have occurred in many locations across the genome, with (AAT)n and (AAC)n repeats being the most common, and (CAG)n and (CCG)n repeats overrepresented. Additionally, the location of triplet expansions across a gene varies by triplet type. Many of these expansions have occurred in the nervous system, and it has therefore been postulated that they may be associated with increased brain complexity.

Triplet repeat expansions have occurred in other species including mice and non-human primates, but the association with triplet repeat expansions and pathogenicity appears to be human specific. It is also possible, though, that pathogenic associations in non-human species have yet to be discovered. In humans, triplet repeat-associated diseases include Huntington’s disease, Friedrich’s ataxia and myotonic dystrophy.

Multiple studies have found human genes that have undergone triplet repeat expansions, and a recent study found 171 genes with greater than ten repeats. In these genes, AGC and CCG repeats predominated. One gene with probable HLS triplet repeat expansion, is the involucrin gene, which has undergone expansion such that the number of repeats increases with phylogenetic proximity to human.