Extended Data Fig. 3: The effect of atypical HTT allele structure on blood somatic expansions does not explain their effect on HD phenotypes and biomarkers.

(a) Schematic representation of the absence of effect of the atypical HTT allele structure on blood somatic expansion in the HD-YAS cohort and of their relative effect on caudate and putamen volumes and on CSF NfL levels after age-by-CAG correction. (b) Graphical representation of the HTT allele structures observed in the HD-YAS cohort. On the left-hand side is the pure CAG tract, which is likely the primary substrate of the somatic HTT repeat instability machinery and is the primary determinant of the rate of somatic HTT repeat expansion and HD pathology. Center, the sequence variants intervening between the CAG and CCG tracts, which define the atypical HTT allele structures observed (that is, CAACAG duplication, CCGCCA loss and CAACAG CCGCCA loss).