A novel polymorphic triplet repeat in intron five of the alpha-synuclein gene: no evidence of expansion or allelic association with idiopathic Parkinson's disease in the Irish.
The recent discovery of two mutations associated with autosomal dominant Parkinson's disease (PD) has led to the hypothesis that the alpha-synuclein gene plays a role in the pathogenesis of PD. Here we report a novel triplet CAA repeat within the unusually large intron 5 sequence of the alpha-synuclein gene. Microsatellite analysis revealed a high degree of polymorphism within the Irish population with seven alleles detected, ranging from eight to 17 CAA repeats. Analysis of the allele/genotype frequency differences observed between an Irish idiopathic PD cohort (eta = 98) and a healthy aged control group ( eta= 92) revealed no strong association with either group. All PD subjects displaying homozygous profiles were examined for expansion of the trinucleotide repeat, but no expansion was observed. These results would suggest that polymorphism of the alpha-synuclein gene may not play as significant a role in the pathogenesis of idiopathic PD as previously hypothesised.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence / Q000235:genetics; D001923:Brain Chemistry / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007438:Introns / Q000235:genetics; D007494:Ireland / Q000208:ethnology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D051843:Synucleins; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein