Abnormal open states patterns in the ATXN2 DNA sequence depends on the CAG repeats length

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Hereditary ataxias are one of the «anticipation diseases» types. Spinocerebral ataxia type 2 occurs when the number of CAG repeats in the coding region of the ATXN2 gene exceeds 34 or more. In healthy people, the CAG repeat region in the ATXN2 gene usually consists of 22–23 CAG trinucleotides. Mutations that increase the length of CAG repeats can cause severe neurodegenerative and neuromuscular disorders known as trinucleotide repeat expansion diseases. The mechanisms causing such diseases are associated with non-canonical configurations that can be formed in the CAG repeat region during replication, transcription or repair. This makes it relevant to study the zones of open states that arise in the region of CAG repeats under torque. The purpose of this work is to study, using mathematical modeling, zones of open states in the region of CAG repeats of the ATXN2 gene, caused by torque. It has been established that the torque effect on the 1st exon of the ATXN2 gene, in addition to the formation of open states in the promoter region, can lead to the formation of additional various sizes open states zones in the CAG repeats region. Moreover, the frequency of additional large zones genesis increases with increasing number of CAG repeats. The inverse of this frequency correlates with the dependence of the disease onset average age on the CAG repeats length. The obtained results will allow us to get closer to understanding the genetic mechanisms that cause trinucleotide repeat diseases.