Slam Gene Family Controlled Pathways to SLE

Slam 基因家族控制的 SLE 通路

• 批准号: 7920853
• 负责人: John D. Rioux
• 金额: $ 17.89万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7920853
• 关键词: Autoimmune Diseases; Cell Communication; Cell Surface Proteins; Cell Surface Receptors; Cells; Chromosomes; Chronic; Clinical; Collection; Disease; Family; Gene Expression; Gene Family; Genes; Genetic; Genetic Variation; Genome; Haplotypes; Human; Immune response; Immune system; Individual; Inflammatory; International; Knowledge; Laboratories; Lead; Maps; Messenger RNA; Pathway interactions; Patients; Pattern; Phase; Predisposition; Public Health; RNA Splicing; Risk; Screening procedure; Spices; Systemic Lupus Erythematosus; Work; cohort; genetic variant; improved; molecular marker; mouse genome; population based; protein expression

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.

该应用程序的长期目标是准确了解遗传变异如何 位于含有SLAM家族细胞表面受体的染色体区域主要可以影响 个体患系统性红斑狼疮 (SLE) 的风险；慢性且使人衰弱 炎症性疾病。 MHC 区域是 1q 染色体上的一个大区域，包含多个基因 参与细胞间相互作用和人体免疫系统免疫反应的控制。 这样的理解将提高我们对导致这种情况和其他潜在情况的机制的了解。 炎症性疾病并可能提供疾病的重要分子标记。这项研究需要充分 还利用了人类和小鼠基因组遗传变异模式的知识 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 区域的初步 SNP 单倍型图以及 国际 HapMap 项目旨在为筛选阶段选择信息最丰富的 SNP 集 协会研究。该 SNP 筛选集将应用于大型特征明确的 SLE 患者 队列。在此屏幕中确定的区域的综合关联映射将在 最大的 SLE 患者和对照集合（基于家庭和人群）。此外，最近的工作还有 证明了不同香料形式的表达对于自身免疫性疾病易感性的重要性， 然而，人们对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 患者和对照个体的免疫相关细胞中表面蛋白的表达。 这项工作有望通过识别影响公共健康的遗传因素来影响公共健康。 个体对系统性红斑狼疮（一种慢性炎症性疾病）的易感性。这项工作将 还提供了可能有助于临床管理的疾病的重要分子标记 使人衰弱的疾病。