UCHL‐1 gene in multiple system atrophy: A haplotype tagging approach

Abstract

To date, the etiology of multiple system atrophy (MSA) has proved impenetrable. We investigated the role of genetic variation in the UCHL‐1 gene in MSA and looked for the presence of disease susceptibility alleles. We determined the linkage disequilibrium structure of the gene and employed a haplotype tagging strategy with power to represent 95% of the haplotype diversity. This approach was performed using a set of tagging single nucleotide polymorphisms (SNPs) that can infer the allelic state of all the common SNPs in UCHL‐1 with a high coefficient of determination. This strategy enabled us to scan across the gene and maintain the power to detect signal(s) from any potential functional variant(s). In 257 Gilman‐probable or ‐definite MSA subjects and 1,536 controls, we did not detect a case–control frequency difference for either the tagged haplotypes or for individual tagging SNPs. This search included the S18Y variant of UCHL‐1, which has been reported to be protective in Parkinson's disease. © 2005 Movement Disorder Society