GENE LINKAGE STUDY OF MULTIPLE SCLEROSIS SIBLING PAIRS

多发性硬化(MS)是一种以炎症为特征的疾病 中枢神经系统白质脱髓鞘。间接法 有证据表明，免疫系统在 多发性硬化症的发病机制和来自双胞胎家族的数据都表明 遗传因素是多发性硬化症的重要决定因素 敏感度 本研究将尝试建立人的染色体定位。 对MS易感基因进行连锁分析 受影响同胞配对法。40个家庭，每个家庭有两个兄弟姐妹 受典型多发性硬化症的影响，将被初步研究，它是 预计每年将增加20个家庭的应计费用 是有可能的。将建立成肌样细胞系 个人。使用DNA多态，受影响的兄弟姐妹将 候选易感基因的共遗传研究 包括T细胞的α、β和伽马链基因 受体，以及传统的分型方法将困惑地评估 人类白细胞抗原和免疫球蛋白基因的遗传。限制性片段 长度多态将被用于研究其他编码基因 对T细胞功能、癌基因和髓鞘重要的蛋白质- 相关基因。是否应确定候选基因组区域： 将搜索整个基因以寻找与多发性硬化症相关的标记 敏感性，重点是高度敏感的使用 多态的，适当间隔的探头。这些探测器将 包括那些检测到可变数目串联重复序列的序列。 一个与多发性硬化易感性连锁的遗传标记的鉴定 应该提供一种直接的方法来描述 易感基因及其在致病过程中的作用 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.