GENE MAPPING IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS

描述：（改编自研究者摘要）系统性狼疮 红斑性狼疮（SLE）是一种病因不明的自身免疫性疾病 其特征在于产生针对自身组织的自身抗体。 SLE是 主要是一种女性疾病，是一种临床异质性疾病， 涉及多个器官系统。 流行病学和家庭 研究令人信服地表明，系统性红斑狼疮在家庭中聚集，这表明 疾病的遗传基础。 SLE的相对危险性 一个有一个狼疮先证者的家庭比对照组高大约10倍 家庭 这一建议的基本假设，基于一个庞大的机构， 证据表明，SLE是一种多基因疾病，具有遗传性。 少数基因对易感性起主要作用。 本申请的总体目标是确定敏感性 人类基因组中的SLE基因座。 这项研究将利用基因 高信息量短串联重复序列多态性（STRP）在 SLE患者的兄弟姐妹 研究设计如下：1） 一项登记了大约300对女性SLE患者及其同胞的研究， 将建立可用的父母。 2)全面的数据库， 将确定以下患者的家族史和临床/血清学信息： 每一个病人。 3)狼疮同胞对血清、DNA、 将开发永生化细胞系和II类MHC基因型。 四、 每个同胞对和可用的父母将使用大约 在基因组筛选中以15至20厘摩（cM）间隔检测200个STRP标记。 5)收集的标记数据的统计遗传分析将用于 检测基因组中对SLE易感的区域， 同胞配对法 一旦关联分析发现可疑区域 在基因组中，将测试额外的标记以缩小基因组的区域。 感兴趣到1- 2cM间隔。 该区域的候选基因将被 将开发研究的和/或重叠的YAC重叠群。 在SLE中使用受累同胞对方法进行基因定位， 许多优点，包括作为模型（继承模式） 独立，具有足够的统计学显著性，以及 提供足够的遗传贡献以最小化异质性问题。 最终确定与SLE遗传相关的基因 将为理解这种疾病的病因提供一个框架， 制定有效的干预策略。

DESCRIPTION: (Adapted from the Investigator's Abstract) Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology characterized the production of autoantibodies against self tissues. SLE is primarily a disease of women, and is a clinically heterogeneous disorder with involvement of multiple organ systems. Epidemiological and family studies have shown convincingly that SLE clusters in families, suggesting a genetic basis for the disease. The relative risk of developing SLE in a family with one lupus proband is approximately 10-fold higher than control families. The underlying hypothesis of this proposal, based on a large body of evidence, is that SLE is a polygenic disease, with the inheritance of a few genes of major effect contributing to susceptibility. The overall objective of this application is to identify the susceptibility loci for SLE within the human genome. The proposed study will utilize gene mapping with highly informative short tandem repeat polymorphism (STRPs) in sibling pairs of women with SLE. The design of the study is as follows: 1) A registry of approximately 300 sib pairs of female SLE patients and their available parents will be established. 2) A comprehensive data base of family history and clinical/serologic information will be established for each patient. 3) A Lupus Sib Pair Biological Resource of serum, DNA, immortalized cell lines, and Class II MHC genotypes will be developed. 4) Each sib pair and available parents will be genotyped using approximately 200 STRP markers in a genome screen at 15 to 20 centiMorgan (cM) intervals. 5) Statistical genetic analysis of the collected marker data will be used to detect regions of the genome which contribute susceptibility to SLE using the sib pair methods. Once linkage analysis has identified suspicious areas of the genome, additional markers will be tested to narrow the region(s) of interest to a 1-2 cM interval. Candidate genes in the region will then be investigated and/or overlapping YAC contigs will e developed. The use of the affected sib pair approach to gene mapping in SLE offers a number of advantages which include being model (mode of inheritance) independent, having sufficient numbers for statistical significance, and providing enough genetic contribution to minimize problems of heterogeneity. The eventual identification of the genes that are genetically linked to SLE will provide a framework for understanding the etiology of this disease and subsequently developing effective intervention strategies.