Fluctuations in Medium Viscosity May Affect the Stability of the CAG Tract in the ATXN2 Gene

Abstract

Background: Trinucleotide repeats are the cause of many neurodegenerative diseases that are currently incurable. In this regard, the question of the causes of occurrence and methods of prevention or treatment of diseases caused by the expansion of repeats in the CAG tract of the ATXN2 gene remains relevant. Previously, it was shown that the frequency of occurrence of additional OS (open states) zones increases with increasing length of the CAG tract, and the value inverse to the frequency correlates with the age of disease onset. Methods: In this work, the influence of the viscosity of the medium and the external torque on the stability of the CAG tract in the ATXN2 gene was studied using mathematical modeling methods. Results: It has been established that the probability of the appearance of additional OS zones of significant size increases with an increase in the CAG of the tract (k > 40 CAG repeats) for all viscosity values, however, at k ≤ 40, the change in viscosity does not significantly affect the probability of additional OS zones in the tract. Conclusions: It was found that under normal conditions (absence of pathology), viscosity does not have a reliable effect on the stability of the DNA molecule, but when pathology appears, an increase in viscosity contributes to an increase in DNA stability, and, accordingly, a decrease has a negative effect on the stabilization of the DNA molecule. In the zone of close to incomplete penetrance of the disease, viscosity does not have a reliable effect on the stability of the CAG tract.