Slam Gene Family Controlled Pathways to SLE

本申请的长期目标是精确了解遗传变异如何 位于含有细胞表面受体的SLAM家族的染色体区域中，主要可以影响 一个人的风险发展系统性红斑狼疮（SLE）;慢性和衰弱 炎症性疾病。MHC区域是染色体1 q上包含多个基因的大区域 参与细胞间相互作用和人体免疫系统中免疫反应的控制。 这样的理解将提高我们对导致这种和潜在的其他机制的认识 炎症性疾病，并可提供重要的疾病分子标志物。这项研究充分考虑了 人类和小鼠基因组中遗传变异模式的知识的优势 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 我们已经创建的SLAM区域的初步SNP单倍型图以及 国际人类基因组单体型图项目，以选择最具信息量的SNPs组用于筛选阶段， 协会研究。该SNPs筛选集将应用于大的、特征良好的SLE患者 同伙在此屏幕中确定的区域的全面关联映射将在 SLE患者和对照组的最大集合（基于家族和人群）。此外，最近的工作 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，对于大多数基因的剪接形式的存在和表达模式知之甚少。 基因组因此，我们将在mRNA水平以及细胞水平上表征基因表达模式。 SLE患者和对照个体免疫相关细胞表面蛋白表达。 这项工作有望通过确定影响遗传因素对公共卫生产生影响。 系统性红斑狼疮是一种慢性炎症性疾病。这项工作将 还提供了重要的疾病分子标志物，可用于临床管理， 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.