Triplet repeat extension, dynamic mutation

Successive identical nucleotide triplets occur in different regions of the human genome. The number of such nucleotide triplets (triplet repeats) at a gene locus is variable in the population as a whole, but is limited to a certain normal range and shows only minor changes within a family over generations. By a mechanism not yet known, the number of triplet repeats can increase beyond a critical threshold. If this excessive number of nucleotide triplet repeats (triplet repeat elongation) is present in the region of genes, it can cause disease. The effects of the increased number of triplet repeats vary, usually causing decreased synthesis or dysfunction of the corresponding protein. A peculiarity of this mutation mechanism is its dynamic nature: once the number of triplet repeats has exceeded the critical value, it can increase from generation to generation (dynamic mutation). Since the degree of expression and the age of manifestation of the diseases are related to the number of triplet repeats, the phenomenon of genetic anticipation (see above) can be explained in this way.