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UCHL‐1 gene in multiple system atrophy: A haplotype tagging approach
Author(s) -
Healy Daniel G.,
AbouSleiman Patrick M.,
Quinn Niall,
Ahmadi Kourosh R.,
Ozawa Tetsutaro,
Kamm Christoph,
Wullner Ullrich,
Oertel Wolfgang H.,
Burk Katrin,
Dupont Erik,
Pellecchia Maria T.,
Tolosa Eduardo,
Gasser Thomas,
Holton Janice L.,
Revesz Tamas,
Goldstein David B.,
Lees Andrew J.,
Wood Nicholas W.
Publication year - 2005
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.20575
Subject(s) - haplotype , linkage disequilibrium , genetics , single nucleotide polymorphism , biology , allele , gene , allele frequency , genotype
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