Trinucleotide repeat expansion

Trinucleotide repeat expansion, also known as 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]

The number of trinucleotide repeats appears to predict the progression, severity, and age of onset of Huntington's disease and similar trinucleotide repeat disorders.[4]

References

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  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 3177194Freely accessible. 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 3073251Freely accessible. PMID 20729633.
  4. ↑ 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 http://80.70.129.162/site/en/weizman.asp?pi=371&doc_id=5042. Retrieved on 2007-12-30.
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