Background Huntington disease (HD) is an inherited neurodegenerative disorder resulting from an expanded CAG-tract in the huntingtin (HTT) gene. Disease prevalence varies worldwide with the highest figures reported in populations of European ancestry. Average CAG-tract size in the general population and population-specific haplotypes have been previously associated with HD prevalence in different regions. HD in South Africa (SA) occurs in all three subpopulations; similar occurrence has been reported in the Caucasian and mixed ancestry groups, with a significantly lower estimate in the black subpopulation.

Aims To assess the distribution of CAG-tract size in the South African general population and to determine what population-specific haplotypes are present in patient and control individuals.

Methods Haplotypes were constructed based on the genotypes of 96 SNPs across the HTT gene, for 72 affected and 311 unaffected chromosomes. CAG-sizing was performed for over 1000 individuals taken from the general population and representative of the three subpopulations. The polymorphic CCG repeat adjacent to the CAG-tract was also investigated in the control cohort.

Results Expanded alleles from Caucasian and mixed ancestry patients were predominantly associated with haplogroup A, signifying a similar European origin; while those from black patients were found on haplogroup B suggesting distinct origins of the mutation. In addition, average CAG-tract size in the general population could be associated with reported minimum prevalence estimates.

Conclusion This data is crucial to the understanding of the genetic background of the HD gene in African populations and may contribute to the development of silencing therapeutics for HD patients.