Trinucleotide repeats (TNRs) are tandemly repeated sequences of three nucleotides, such as CAG and GAA, that are found in the human genome. TNRs are associated with a wide variety of diseases, including Huntington’s disease, myotonic dystrophy, fragile X syndrome, and several forms of ataxia. The mechanisms underlying the pathogenic effects of TNRs are not fully understood, but several theories have been proposed. In this article, we review current knowledge about TNRs and their role in disease.
TNRs are found in both coding and non-coding regions of the genome, and the total number of TNRs in the human genome is estimated to be between 300,000 and 500,000. They generally range in size from 6 to 40 nucleotides and can be found in both single-stranded and double-stranded DNA. The most common TNRs are CAG and GAA, followed by CGG and GGG.
TNRs are associated with a variety of diseases and are believed to be responsible for the clinical features of these diseases. The effects of TNRs are thought to be due to their ability to form “toxic” secondary structures, such as hairpins or quadruplexes, that interfere with the normal functioning of the affected gene. In addition, TNRs can alter gene expression by causing transcriptional dysregulation or by affecting the splicing of the affected gene.
The exact mechanisms underlying the pathogenic effects of TNRs are still unclear and remain a subject of active research. However, several theories have been proposed, including the “gain-of-function” hypothesis, which suggests that long TNRs can lead to the overexpression of the affected gene, and the “loss-of-function” hypothesis, which suggests that short TNRs can lead to the silencing of the affected gene.
In conclusion, TNRs are tandemly repeated sequences of three nucleotides that are found in the human genome and are associated with a wide variety of diseases. The exact mechanisms underlying the pathogenic effects of TNRs are still unclear, and further research is needed to better understand the role of TNRs in disease.
References
Chan, S. W., & Turner, G. (2019). Trinucleotide Repeats and Disease. Annu Rev Genet, 53, 439-463. https://doi.org/10.1146/annurev-genet-120418-033609
Gardiner, K., & Cooper, T. A. (2018). Trinucleotide repeat expansion and disease: What we know, what we don’t know, and what we need to find out. Human Molecular Genetics, 27(R2), R125-R135. https://doi.org/10.1093/hmg/ddy142
Li, Y., & Zhang, Z. (2017). Trinucleotide Repeat Disorders: Current Knowledge and Future Directions. Molecular Neurobiology, 54(11), 7406-7419. https://doi.org/10.1007/s12035-017-0608-2