Slam Gene Family Controlled Pathways to SLE

这项应用的长期目标是获得对遗传变异如何 位于含有SLAM家族的细胞表面受体的染色体区域主要可以影响 个人患系统性红斑狼疮(SLE)的风险；一种慢性的、使人衰弱的疾病 炎症性疾病。MHC区域是染色体1q上的一个包含多个基因的大区域 参与细胞间的相互作用和控制人类免疫系统中的免疫反应。 这样的理解将提高我们对导致这种情况和潜在的其他情况的机制的了解 炎症性疾病，并可能提供疾病的重要分子标志物。这项研究需要完整的 人类和小鼠基因组中遗传变异模式的知识也具有优势 作为相关的技术平台(实验室和分析)。特别是，这个项目利用了 我们创建的SLAM区域的SNP单倍型初步图谱以及 国际HapMap项目，以选择信息最丰富的一组SNPs用于筛查阶段 联想研究。这套SNPs筛查将应用于具有良好特征的大型SLE患者 一群人。本屏幕中确定的区域的全面关联地图将在 系统性红斑狼疮患者和对照的最大集合(以家庭和人口为基础)。此外，最近的工作已经 证明了不同香料形式的表达在自身免疫性疾病易感性中的重要性 然而，人们对大多数基因剪接形式的存在和表达方式知之甚少。 基因组。因此，我们将在mRNA和细胞水平上表征基因表达模式 SLE患者和对照组免疫相关细胞表面蛋白的表达。 这项工作承诺通过确定影响人类健康的遗传因素对公众健康产生影响。 个人对系统性红斑狼疮的易感性，一种慢性炎症性疾病。这项工作将 也提供了疾病的重要分子标记，这可能在临床治疗中有用 使人衰弱的疾病。

The long term objectives of this application are to obtain a precise understanding of how genetic variants located in the chromosomal region containing the SLAM family of cell surface receptors major can influence an individual's risk to developing systemic lupus erythematosus (SLE); a chronic and debilitating inflammatory disease. The MHC region is a large region on chromosome 1q that contains multiple genes that are involved in cell-cell interactions and control of the immune response in the human immune system. Such an understanding will improve our knowledge of the mechanisms that lead to this and potentially other inflammatory diseases and may provide important molecular markers of disease. This study takes full advantage of the knowledge of the patterns of genetic variation in the human and mouse genomes as well as the relevant technological platforms (laboratory and analytical). In particular this project takes advantage of the preliminary SNP haplotype map of the SLAM region that we have created as well as that of the International HapMap project in order to select the most informative set of SNPs for the screening phase of the association study. This screening set of SNPs will be applied to large well-charcterized SLE patient cohorts. Comprehensive association mapping of the regions identified in this screen will be pursued in the largest collection of SLE patients and controls (family- and population-based). In addition, recent work has demonstrated the importance of expression of different spice forms in susceptibility to autoimmune disease, however very little is known about the existence and expression patterns of splice forms of most genes in the genome. We will therefore characterize the gene expression pattern at the level of mRNA as well as cell surface protein expression in immunologically relevant cells from SLE patients and control individuals. This work promises to have an impact on public health by identifying the genetic factors that influence an individual's susceptibility to systemic lupus erythematosus, a chronic inflammtory disease. This work will also provide important molecular markers of diseases that may be useful in clinical mangement of this debilitating disease.