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

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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 (2008) SNP mapping and candidate gene sequencing in the class I region of the HLA complex: searching for multiple sclerosis susceptibility genes in Tasmanians. Tissue Antigens, 71 (1). pp. 42-50. ISSN 0001-2815

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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
[ubiquitinD(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 overtransmitted
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 IMS
susceptibility genes.

Item Type: Article
Keywords: class I • HLA complex • multiple sclerosis • susceptibility • Tasmania
Journal or Publication Title: Tissue Antigens
Page Range: pp. 42-50
ISSN: 0001-2815
Identification Number - DOI: 10.1111/j.1399-0039.2007.00962.x
Additional Information:

The definitive published version is available online at: http://interscience.wiley.com

Date Deposited: 02 Jul 2008 04:34
Last Modified: 18 Nov 2014 03:44
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