GENE LINKAGE STUDY OF MULTIPLE SCLEROSIS SIBLING PAIRS

多发性硬化症（MS）是一种以炎症为特征的疾病 和中枢神经系统白色物质脱髓鞘。 间接 有证据表明，免疫系统在 MS的发病机制，以及来自家族所有双胞胎研究的数据表明， 遗传因素是MS的重要决定因素 易感性 这项研究将试图建立染色体定位， MS易感基因或基因的连锁分析，使用 影响同胞配对法。 四十个家庭，每个家庭有两个兄弟姐妹 受典型MS的影响，将进行初步研究， 预计每年增加20个家庭， 是可能的。 将从所有动物中建立类Limphoblastoid系， 个体 使用DNA多态性，受影响的兄弟姐妹将 研究候选易感基因的共遗传 包括T细胞的α、β和γ链基因 受体，传统的分型方法将被用来评估 HLA和免疫球蛋白基因遗传。 限制性片段 长度多态性将被用来研究其他基因编码 对T细胞功能、致癌和髓磷脂很重要的蛋白质， 相关基因 如果没有候选基因组区域：被识别 整个基因将被搜索与MS相关的标记 敏感性，重点放在使用高度 多态的，适当间隔的探针。 这些探测器将 包括检测可变数目串联重复序列那些。 与MS易感性相关的遗传标记的鉴定 应该提供一个直接的方法来描述 易感基因，并了解其作用， MS的发病机制

Multiple sclerosis (MS) is a disease characterized by inflammation and demyelination in central nervous system white matter. Indirect evidence suggests that the immune system plays a role in the pathogenesis of MS, and data from family all twin studies indicate that genetic factors are important determinants of MS susceptibility This study will attempt to establish the chromosomal location of the MS susceptibility gene or genes by linkage analysis using the affected sib pair method. Forty families, each with two siblings affected with typical MS, will be studied initially, and it is anticipated that accrual of an additional 20 families per year will be possible. Limphoblastoid lines will be established from all individuals. Using DNA polymorphisms, affected siblings will be studied for co-inheritance of candidate susceptibility genes including the alpha, beta and gamma chain genes of the T-cell receptor, and traditional typing methods will bemused to assess inheritance of HLA and immunoglobulin genes. Restriction fragment length polymorphisms will bemused to study other genes encoding proteins important for T-cell function, oncogenies, and myelin- related genes. Should no candidate genomic region: be identified the entire genes will be searched for markers linked to MS susceptibility, with emphasis placed on the use of highly polymorphic, appropriately spaced probes. These probes will include those detecting variable number tandem repeat" sequences. Identification of a genetic marker linked to MS susceptibility should provide a direct approach to the characterization of the susceptibility gene and to an understanding of its role in the pathogenesis of MS.