Distribution of the CAG Triplet Repeat in ATXN1 , ATXN3 , and CACNA1A Loci in Peruvian Population

AbstractSpinocerebellar ataxia subtypes 1, 3, and 6 (SCA1, MJD/SCA3, and SCA6) are among the most prevalent autosomal dominant cerebellar ataxias worldwide, but their relative frequencies in Peru are low. Frequency of large normal (LN) alleles at spinocerebellar ataxia-causative genes has been proposed to be associated with disease prevalence. To investigate the allelic distribution of the CAG repeat inATXN1,ATXN3, andCACNA1A genes in a Peruvian mestizo population and examine their association with the relative frequency of SCA1, MJD/SCA3, and SCA6 across populations. We genotyped 213 healthy mestizo individuals from Northern Lima, Peru, forATXN1,ATXN3, andCACNA1A using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE). We compared the frequency of LN alleles and relative disease frequency between populations. We also tested 40 samples for CAT repeat interruptions within the CAG tract ofATXN1. We found no association between disease frequency and population frequency of LN alleles atATXN1 andATXN3. All 40ATXN1 samples tested for CAT interruptions were positive. Frequency of LN alleles atCACNA1A correlates with SCA6 frequency across several populations, but this effect was largely driven by data from a single population. Low frequency of SCA1 and MJD/SCA3 in Peru is not explained by frequency of LN alleles atATXN1 andATXN3, respectively. The observed correlation betweenCACNA1A LN alleles and SCA6 frequency requires further assessment.
Source: The Cerebellum - Category: Neurology Source Type: research