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

Burfoot, RK; Jensen, CJ; Field, J; Stankovich, J; Varney, MD; Johnson, LJ; Butzkueven, H; Booth, D; Bahlo, M; Tait, BD; Taylor, BV; Speed, TP; Heard, R; Stewart, GJ; Foote, SJ; Kilpatrick, TJ; Rubio, JP

Author(s): Burfoot, RK; Jensen, CJ; Field, J; Stankovich, J; Varney, MD; Johnson, LJ; Butzkueven, H; Booth, D; Bahlo, M; Tait, BD; Taylor, BV; Speed, TP; Heard, R; Stewart, GJ; Foote, SJ; Kilpatrick, TJ; Rubio, JP;
Details: Publication Year 2008-01,Volume 71,Issue #1,Page 42-50
Journal Title: TISSUE ANTIGENS
Publication Type: Journal Article
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.
Publisher: BLACKWELL PUBLISHING
Keywords: MYELIN OLIGODENDROCYTE GLYCOPROTEIN; DIAGNOSTIC-CRITERIA; ASSOCIATIONS; HAPLOTYPES; POLYMORPHISMS; DISEASE; IDENTIFICATION; POPULATION; DISSECTION; GUIDELINES
Publisher's Version: https://doi.org/10.1111/j.1399-0039.2007.00962.x
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-01-01 12:00:00