CAG-Expansion Haplotype Analysis in a Population with a Low Prevalence of Huntington’s Disease

다국어 초록 (Multilingual Abstract)

Background and Purpose The prevalence of Huntington’s disease (HD) among East Asiansis less than one-tenth of that among Caucasians. Such a low prevalence may be attributable to alack of carriers of specific predisposing haplogroups associated with the high instability of theHuntingtin gene (HTT). The aim of this study was to evaluate the association between specificHTT haplogroups and the occurrence of HD in a Thai population.
Methods CAG-repeat sizes and HTT haplotypes were analyzed in 18 Thai HD patients and215 control subjects. Twenty-two tagging single-nucleotide polymorphisms (tSNPs) were genotyped. Results Only 18 patients from 15 unrelated families were identified over the last 17 years. Pathological CAG-repeat alleles ranged from 39 to 48 repeats (43.5±3.0, mean±SD), and normal alleles ranged from 9 to 24 repeats (16.49±1.74). Only two of the chromosomes studiedcomprised intermediate alleles. Unlike the Caucasian data, all but 1 of the 22 tSNPs were notassociated with the occurrence of HD. The predisposing haplogroups for Caucasian HD (haplogroups A1 and A2) are very rare in Thai patients (<4%). Both HD and normal chromosomesare commonly haplogroups A5 and C, in contrast to the case for Chinese and Japanese patients,in whom only haplogroup C was common in HD chromosomes. The frequency of CAG-repeatsizes of haplogroup A5 and C were also similarly distributed. Conclusions HD chromosomes of Thai patients may arise randomly from each haplogroup, with a similar mutation rate. This rate is much lower than the CAG expansions from Caucasian HD haplogroups. These data suggest that the different mechanisms underlie CAG expansion in Thai and Caucasian patients.

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