GENE MAPPING IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS

描述：(改编自《调查者摘要》)系统性狼疮 摘要红斑狼疮是一种病因不明的自身免疫性疾病。 以产生针对自身组织的自身抗体为特征。SLE是 主要是一种女性疾病，是一种临床上的异质性疾病 累及多个器官系统。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，表明 这种疾病的遗传基础。发生系统性红斑狼疮的相对风险 有一个狼疮先证者的家庭大约是对照组的10倍 家人。这一建议的基本假设是建立在一个大机构的基础上 有证据表明，SLE是一种多基因疾病，具有一种遗传性 影响易感性的主效基因很少。 此应用程序的总体目标是识别敏感度 人类基因组中SLE的基因座。拟议的研究将利用基因 高信息量短串联重复序列多态(STRPs)在中国的定位 一对患有系统性红斑狼疮的兄弟姐妹。研究设计如下：1) 大约300对女性系统性红斑狼疮患者及其同胞的登记 将建立可用的家长。2)全面的数据库 将为以下患者建立家族史和临床/血清学信息 每一位病人。3)一对狼疮同胞的血清、DNA、 永生化细胞系和第二类MHC基因型将被开发出来。4) 每对兄弟姐妹和可用的双亲将使用大约 在基因组筛查中以15到20厘米摩根(Cm)的间隔筛选200个STRP标记。 5)对收集的标记数据进行统计遗传分析将用于 检测与系统性红斑狼疮易感性有关的基因组区域 同胞配对方法。一旦连锁分析确定了可疑区域 将测试更多的标记以缩小基因组的区域(S) 对1-2厘米的间隔感兴趣。然后，该区域的候选基因将是 将开发已调查和/或重叠的YAC重叠群。 在SLE中使用受影响的同胞对方法进行基因定位提供了一种 许多优势，包括模范(继承模式) 独立的，具有足够的统计意义的数字，以及 提供足够的遗传贡献，将异质性问题降至最低。 最终确定与系统性红斑狼疮有遗传关联的基因 将为理解这种疾病的病因提供一个框架， 随后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.