UCHL-1 gene in multiple system atrophy: a haplotype tagging approach.
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.
Healy
Daniel G
DG
Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London United Kingdom.
Abou-Sleiman
Patrick M
PM
Quinn
Niall
N
Ahmadi
Kourosh R
KR
Ozawa
Tetsutaro
T
Kamm
Christoph
C
Wullner
Ullrich
U
Oertel
Wolfgang H
WH
Burk
Katrin
K
Dupont
Erik
E
Pellecchia
Maria T
MT
Tolosa
Eduardo
E
Gasser
Thomas
T
Holton
Janice L
JL
Revesz
Tamas
T
Goldstein
David B
DB
Lees
Andrew J
AJ
Wood
Nicholas W
NW
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*
C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase