Insights into the mutational history and prevalence of SCA1 in the Indian population through anchored polymorphisms.

There is a wide variation in prevalence of spinocerebellar ataxia type 1 (SCA1) in different populations. In the present study, we observed SCA1 in approximately 22% (37/167 families) of the autosomal dominant cerebellar ataxias (ADCAs) in the Indian population. We investigated the role of various genetic factors like repeat length, interruption pattern and chromosomal background in predisposing the repeats to instability in these families. We analyzed 12 markers (9 SNPs and 3 microsatellite markers) and found 3 of them, spanning a region of approximately 65 kbp to be linked with the disease locus in the Indian population. The haplotype C-4-C defined by rs1476464 (SNP9)-D6S288-rs2075974 (SNP1), which was extremely rare in nonaffected chromosomes (approximately 3%), was observed to be significantly (P<0.0000) associated with the expanded chromosomes in approximately 44% of SCA1 families. This haplotype was found in all nonhuman primates. SNP1 (C/T), which showed a skewed allelic distribution between large (LN > 30 repeats) and small normal (SN