title: 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.
authors: Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London United Kingdom.
authors: Daniel G
authors: DG
authors: Healy
authors: Patrick M
authors: PM
authors: Abou-Sleiman
authors: Niall
authors: N
authors: Quinn
authors: Kourosh R
authors: KR
authors: Ahmadi
authors: Tetsutaro
authors: T
authors: Ozawa
authors: Christoph
authors: C
authors: Kamm
authors: Ullrich
authors: U
authors: Wullner
authors: Wolfgang H
authors: WH
authors: Oertel
authors: Katrin
authors: K
authors: Burk
authors: Erik
authors: E
authors: Dupont
authors: Maria T
authors: MT
authors: Pellecchia
authors: Eduardo
authors: E
authors: Tolosa
authors: Thomas
authors: T
authors: Gasser
authors: Janice L
authors: JL
authors: Holton
authors: Tamas
authors: T
authors: Revesz
authors: David B
authors: DB
authors: Goldstein
authors: Andrew J
authors: AJ
authors: Lees
authors: Nicholas W
authors: NW
authors: Wood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020224:Expressed Sequence Tags / Q000378:metabolism*; D005260:Female; D015723:Gene Library; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase