A common SNP haplotype provides molecular proof of a founder effect of Huntington disease linking two South African populations.

This study involved the detailed investigation of the region surrounding the huntingtin gene in families with a history of Huntington Disease (HD) in South Africa. The primary aim was to investigate the origins of the HD mutation in South Africa by constructing a single-nucleotide polymorphism (SNP) haplotype around the HD gene and to determine how many haplotypes there are in two different South African populations. Haplotypes were created by genotyping six SNPs in a total of 13 HD families--seven Caucasian and six Mixed Ancestry. Of the six Mixed Ancestry families, four shared a common SNP haplotype, which was observed in two Afrikaans-speaking Caucasian HD families thus indicating that a founder effect was present in the South African population. The genotyping of a recently identified highly polymorphic marker close to the HD disease-causing mutation further corroborated the SNP haplotype results. Computational analysis was used to analyze the extent of the common haplotype identified in the study cohort in additional South African HD individuals. The results strongly suggest that the common haplotype extends further into the South African Mixed Ancestry HD population and is predominant in the Mixed Ancestry HD families.