More thoughts on these issues here: If genomics is the answer, what's the question? www.wiringthebrain.com/2018/12/if-g...

Most previous epigenetic age predictors were focused on DNA methylation. Our own model suggested nucleosome positioning as an age predictor a year ago onlinelibrary.wiley.com/doi/full/10....

Thank you so much to everyone who contributed to this work which resulted in a fascinating insight into #RepeatExpansions

These results indicate that THAP11 expansions are rare in the British population and that sequence structures predisposed to expansions may be more common in non-British ancestries.

We showed a linear relationship between the number of CAA interruptions and overall repeat length. Furthermore, we showed that the prevalence of alleles with three CAA interruptions (characteristic of the disease-causing alleles) is most common in African and South Asian genetic ancestries.

We identified expanded repeats in four individuals with learning difficulties without ataxia and in three individuals in UK Biobank, one with hereditary ataxia (also highlighted by Fearnley et al. (2024)), one with hereditary neuropathy, and one with neurodegenerative disease. See an exemplary case:

We explored the repeat size and structure by interrogating data from from Genomics England, the UCL Queen Square Institute of Neurology in-house database (UCL IoN), and the UK Biobank.

Tan et al. (2023) found a CAG repeat expansion in THAP11 was recently found to be associated with spinocerebellar ataxia in two Chinese families. Expanded repeats ranged from 45 to 100 units, with CAA sequence interruptions in the 5′ region and an uninterrupted CAG tract in the 3′ tail.

congrats Emma!