A genome-wide screen for susceptibility loci in ankylosing spondylitis

Brown, Matthew A., Pile, Kevin D., Kennedy, L. Gail, Campbell, Duncan, Andrew, Lee, March, Ruth, Shatford, Jane L., Weeks, Daniel E., Calin, Andrei and Wordsworth, B. Paul (1998) A genome-wide screen for susceptibility loci in ankylosing spondylitis. Arthritis and Rheumatism, 41 4: 588-595. doi:10.1002/1529-0131(199804)41:4<588::AID-ART5>3.0.CO;2-0


Author Brown, Matthew A.
Pile, Kevin D.
Kennedy, L. Gail
Campbell, Duncan
Andrew, Lee
March, Ruth
Shatford, Jane L.
Weeks, Daniel E.
Calin, Andrei
Wordsworth, B. Paul
Title A genome-wide screen for susceptibility loci in ankylosing spondylitis
Journal name Arthritis and Rheumatism   Check publisher's open access policy
ISSN 0004-3591
1529-0131
Publication date 1998-04-01
Sub-type Article (original research)
DOI 10.1002/1529-0131(199804)41:4<588::AID-ART5>3.0.CO;2-0
Volume 41
Issue 4
Start page 588
End page 595
Total pages 8
Place of publication Hoboken. N.J., U.S.A.
Publisher John Wiley & Sons
Language eng
Subject 0604 Genetics
110322 Rheumatology and Arthritis
Formatted abstract
Objective.
To localize the regions containing genes that determine susceptibility to ankylosing spondylitis (AS).

Methods.
One hundred five white British families with 121 affected sibling pairs with AS were recruited, largely from the Royal National Hospital for Rheumatic Diseases AS database. A genome-wide linkage screen was undertaken using 254 highly polymorphic microsatellite markers from the Medical Research Council (UK) (MRC) set. The major histocompatibility complex (MHC) region was studied more intensively using 5 microsatellites lying within the HLA class III region and HLA-DRB1 typing. The Analyze package was used for 2-point analysis, and GeneHunter for multipoint analysis.

Results
.
When only the MRC set was considered, 11 markers in 7 regions achieved a P value of ≤0.01. The maximum logarithm of odds score obtained was 3.8 (P = 1.4 x 10-5) using marker D6S273, which lies in the HLA class III region. A further marker used in mapping of the MHC class III region achieved a LOD score of 8.1 (P = 1 x 10-9). Nine of 118 affected sibling pairs (7.6%) did not share parental haplotypes identical by descent across the MHC, suggesting that only 31% of the susceptibility to AS is coded by genes linked to the MHC. The maximum non-MHC LOD score obtained was 2.6 (P = 0.0003) for marker D16S422.

Conclusion.
The results of this study confirm the strong linkage of the MHC with AS, and provide suggestive evidence regarding the presence and location of non-MHC genes influencing susceptibility to the disease.
Keyword Complex Traits
Linkage
HLA-B27
HLA
Disease
Risk
Homozygosity
Population
Arthritis
Family
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Tue, 07 Sep 2010, 20:01:34 EST