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SNP mapping and candidate gene sequencing in the class 1 region of the HLA complex: searching for multiple sclerosis susceptibility genes in Tasmanians

Citation

Burfoot, RK and Jensen, CJ and Field, J and Stankovich, J and Varney, MD and Johnson, LJ and Butzkueven, H and Booth, D and Bahlo, M and Tait, BD and Taylor, BV and Speed, TP and Heard, R and Stewart, GJ and Foote, SJ and Kilpatrick, TJ and Rubio, JP, SNP mapping and candidate gene sequencing in the class 1 region of the HLA complex: searching for multiple sclerosis susceptibility genes in Tasmanians, Tissue Antigens, 71, (Oct 30) pp. 42-50. ISSN 0001-2815 (2008) [Refereed Article]

DOI: doi:10.1111/j.1399-0039.2007.00962.x

Abstract

This study is an extension to previously published work that has linked variation in the human leukocyte antigen (HLA) class I region with susceptibility to multiple sclerosis (MS) in Australians from the Island State of Tasmania. Single nucleotide polymorphism (SNP) mapping was performed on an 865-kb candidate region (D6S1683-D6S265) in 166 Tasmanian MS families, and seven candidate genes [ubiquitin D (UBD), olfactory receptor 2H3 (OR2H3), gamma-aminobutyric acid B receptor 1 (GABBR1), myelin oligodendrocyte glycoprotein (MOG), HLA-F, HLA complex group 4 (HCG4) and HLA-G] were resequenced. SNPs tagging the extended MS susceptibility haplotype were genotyped in an independent sample of 356 Australian MS trios and SNPs in the MOG gene were significantly over-transmitted to MS cases. We identified significant effects on MS susceptibility of HLA-A*2 (OR: 0.51; P = 0.05) and A*3 (OR: 2.85; P = 0.005), and two coding polymorphisms in the MOG gene (V145I: P = 0.01, OR: 2.2; V142L: P = 0.04, OR: 0.45) after full conditioning on HLA-DRB1. We have therefore identified plausible candidates for the causal MS susceptibility allele, and although not conclusive at this stage, our data provide suggestive evidence for multiple class I MS susceptibility genes.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Genetics not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Inherited Diseases (incl. Gene Therapy)
Author:Stankovich, J (Dr Jim Stankovich)
Author:Taylor, BV (Professor Bruce Taylor)
Author:Foote, SJ (Professor Simon Foote)
ID Code:48820
Year Published:2008
Web of Science® Times Cited:34
Deposited By:Menzies Institute for Medical Research
Deposited On:2007-08-01
Last Modified:2011-08-03
Downloads:0

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