A model for the dynamics of expanded CAG repeat alleles: ATXN2 and ATXN3 as prototypes.

ABSTRACT: Background: Spinocerebellar ataxia types 2 (SCA2) and 3 (SCA3/MJD) are diseases due to dominant unstable expansions of CAG repeats (CAGexp). Age of onset of symptoms (AO) correlates with the CAGexp length. Repeat instability leads to increases in the expanded repeats, to important AO anticipations and to the eventual extinction of lineages. Because of that, compensatory forces are expected to act on the maintenance of expanded alleles, but they are poorly understood. Objectives: we described the CAGexp dynamics, adapting a classical equation and aiming to estimate for how many generations will the descendants of a de novo expansion last. Methods: A mathematical model was adapted to encompass anticipation, fitness, and allelic segregation; and empirical data fed

SUBMITTER: Sena LS 

PROVIDER: S-EPMC10682950 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature