Background Simple sequence repeats such as CAG trinucleotide repeats in the huntingtin gene (HTT) are regarded as a source which provides normal variation in the genetic trait they are associated with. The current study examines the influence of CAG repeat length on structural and functional modification of the normal brain.
Methods Standardised measures of behaviour, motor and executive function, as well as MRI scans were obtained from 56 children (ages 6–18 years). All of the participants came from HD families, however, were tested (for research purposes only) to have CAG repeats within the normal range. The relationship between CAG repeat length and quantitative measures of brain structure and function were determined with linear regression models.
Results Children with longer CAG repeats, yet still below disease threshold, showed 1) fewer problematic behaviours and lower incidence of behavioural/psychiatric diagnosis; 2) superior fine motor skill and 3) superior visuo-spatial skills and executive function (verbal fluency). In regard to brain morphology, increasing CAG repeats were associated with volume of the striatum and cerebellum, 2 key brain regions governing both motor and behavioural functions.
Conclusions The results suggest that increase in CAG repeat length within the normal range mediates advantageous changes of structure and function of the brain. Larger CAG repeats may sculpt a neural circuit in which the cerebellum and striatum are optimised for maximal motor, behavioural, cognitive function.
- CAG repeat
- normal brain
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