title: Huntington disease in the South African population occurs on diverse and ethnically distinct genetic haplotypes.
abstract: Huntington disease (HD) is a neurodegenerative disorder resulting from the expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene. Worldwide prevalence varies geographically with the highest figures reported in populations of European ancestry. HD in South Africa has been reported in Caucasian, black and mixed subpopulations, with similar estimated prevalence in the Caucasian and mixed groups and a lower estimate in the black subpopulation. Recent studies have associated specific HTT haplotypes with HD in distinct populations. Expanded HD alleles in Europe occur predominantly on haplogroup A (specifically high-risk variants A1/A2), whereas in East Asian populations, HD alleles are associated with haplogroup C. Whether specific HTT haplotypes associate with HD in black Africans and how these compare with haplotypes found in European and East Asian populations remains unknown. The current study genotyped the HTT region in unaffected individuals and HD patients from each of the South African subpopulations, and haplotypes were constructed. CAG repeat sizes were determined and phased to haplotype. Results indicate that HD alleles from Caucasian and mixed patients are predominantly associated with haplogroup A, signifying a similar European origin for HD. However, in black patients, HD occurs predominantly on haplogroup B, suggesting several distinct origins of the mutation in South Africa. The absence of high-risk variants (A1/A2) in the black subpopulation may also explain the reported low prevalence of HD. Identification of haplotypes associated with HD-expanded alleles is particularly relevant to the development of population-specific therapeutic targets for selective suppression of the expanded HTT transcript.
authors: 1] Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa [2] Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Fiona K
authors: FK
authors: Baine
authors: Chris
authors: C
authors: Kay
authors: Maria E
authors: ME
authors: Ketelaar
authors: Jennifer A
authors: JA
authors: Collins
authors: Alicia
authors: A
authors: Semaka
authors: Crystal N
authors: CN
authors: Doty
authors: Amanda
authors: A
authors: Krause
authors: L Jacquie
authors: LJ
authors: Greenberg
authors: Michael R
authors: MR
authors: Hayden
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D006239:Haplotypes; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013019:South Africa; D044465:White People / Q000235:genetics*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins