SNP mapping and candidate gene sequencing in the class I region of the HLA complex: searching for multiple sclerosis susceptibility genes in Tasmanians
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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DOI：
10.1111/j.1399-0039.2007.00962.x
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发表时间：
2008-01-01
期刊：
影响因子：
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通讯作者：
Rubio, J. P.
中科院分区：
文献类型：
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作者：
Burfoot, R. K.;Jensen, C. J.;Rubio, J. P.
这项研究是对先前发表的工作的延伸，该工作将人类白细胞抗原（HLA）I类区域的变异与塔斯马尼亚岛州澳大利亚人对多发性硬化症（MS）的易感性联系起来。对865-kb的候选区域进行单核苷酸多态性（SNP）作图（D 6S 1683-D 6S 265）和7个候选基因[泛素D（UBD）、嗅觉受体2 H3（OR 2 H3）、γ-氨基丁酸B受体1（GABBR 1）、髓鞘少突胶质细胞糖蛋白（MOG）、HLA-F、对HLA复合物组4（HCG 4）和HLA-G]进行重新测序。在356个澳大利亚MS三重奏的独立样本中对标记扩展MS易感性单倍型的SNP进行了基因分型，并且MOG基因中的SNP显着过度传播给MS病例。我们确定了HLA-DRB 1完全调节后，HLA-A*2（OR：0.51; P = 0.05）和A*3（OR：2.85; P = 0.005）以及MOG基因中的两个编码多态性（V145 I：P = 0.01，OR：2.2; V142 L：P = 0.04，OR：0.45）对MS易感性的显著影响。因此，我们已经确定了合理的候选人的因果MS易感等位基因，虽然在这个阶段还没有定论，我们的数据提供了多个I类MS易感基因的提示性证据。
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.