Trinucleotide repeat expansion

A trinucleotide repeat expansion, also known as a triplet repeat expansion, is the DNA mutation responsible for causing any type of disorder categorized as a trinucleotide repeat disorder. These are labelled in dynamical genetics as dynamic mutations.[1] Triplet expansion is caused by slippage during DNA replication, also known as "copy choice" DNA replication.[2] Due to the repetitive nature of the DNA sequence in these regions, 'loop out' structures may form during DNA replication while maintaining complementary base pairing between the parent strand and daughter strand being synthesized. If the loop out structure is formed from the sequence on the daughter strand this will result in an increase in the number of repeats. However, if the loop out structure is formed on the parent strand, a decrease in the number of repeats occurs. It appears that expansion of these repeats is more common than reduction. Generally, the larger the expansion the more likely they are to cause disease or increase the severity of disease. Other proposed mechanisms for expansion and reduction involve the interaction of RNA and DNA molecules.[3]

In addition to occurring during DNA replication, trinucleotide repeat expansion can also occur during DNA repair.[4] When a DNA trinucleotide repeat sequence is damaged, it may be repaired by processes such as homologous recombination, non-homologous end joining, mismatch repair or base excision repair. Each of these processes involves a DNA synthesis step in which strand slippage might occur leading to trinucleotide repeat expansion.[4]

The number of trinucleotide repeats appears to predict the progression, severity, and age of onset of Huntington's disease and similar trinucleotide repeat disorders.[5] Other human diseases in which triplet repeat expansion occurs are fragile X syndrome, several spinocerebellar ataxias, myotonic dystrophy and Friedreich's ataxia.[4]


  1. ^ Richards RI, Sutherland GR (1997). "Dynamic mutation: possible mechanisms and significance in human disease". Trends Biochem. Sci. 22 (11): 432–6. doi:10.1016/S0968-0004(97)01108-0. PMID 9397685.
  2. ^ Salinas-Rios V, Belotserkovskii BP, Hanawalt PC (2011). "DNA slip-outs cause RNA polymerase II arrest in vitro: potential implications for genetic instability". Nucleic Acids Res. 39 (15): 1–11. doi:10.1093/nar/gkr429. PMC 3177194. PMID 21666257.
  3. ^ McIvor EI, Polak U, Napierala M (2010). "New insights into repeat instability: Role of RNA•DNA hybrids". RNA Biol. 7 (5): 551–8. doi:10.4161/rna.7.5.12745. PMC 3073251. PMID 20729633.
  4. ^ a b c Usdin K, House NC, Freudenreich CH (2015). "Repeat instability during DNA repair: Insights from model systems". Crit. Rev. Biochem. Mol. Biol. 50 (2): 142–67. doi:10.3109/10409238.2014.999192. PMC 4454471. PMID 25608779.
  5. ^ News Release, Weizmann Institute of Science, "Scientists at the Weizmann Institute, using computer simulations, have provided an explanation as to why certain genetic diseases caused by repeats in the code are “genetic time-bombs” whose onset and progression can be accurately predicted," November 21, 2007, at Retrieved on 2007-12-30.