ROLE OF NULL GENE POLYMORPHISMS IN LUPUS GENETICS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 B。 申请COBRE资助的研究经验建议 系统性红斑狼疮（SLE）是一种复杂的慢性自身免疫性疾病，具有多器官受累，目前尚不完全清楚。SLE的遗传起源得到高遗传率（66%）、家族聚集性、单卵双胞胎一致性增加、遗传连锁和候选基因遗传关联（包括HLA等位基因、Fc受体和补体成分）的支持。相关的环境因素可能包括感染、治疗、个人习惯（吸烟）和饮食。 本研究探讨了该疾病的遗传相关性，具体目标如下： 具体目标1：使用DNA池技术，以确定非编码区的SNPs与SLE在欧洲-美国（EA）的人口。 具体目标二：使用至少两个基因分型平台对目标1中确定的区域进行多次精细作图实验，以表征个体相关SNP。 具体目标3：作为功能研究的一部分，对目标2中确定的“风险”和“非风险”单倍型进行表达和结构分析。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. B. Research Experience Proposed for COBRE Grant Application Systemic lupus erythematosus (SLE) is a complex, chronic and only partially-understood autoimmune disorder with multiple organ involvement. Genetic origins for SLE are supported by high heritability (66%), familial aggregation, increased monozygotic twin concordance, genetic linkages, and candidate gene genetic association, including HLA alleles, Fc receptors, and complement components. Relevant environmental factors likely include infections, therapeutics, personal habits (smoking), and diet. This study explores genetic associations of the disease with the following specific aims: Specific Aim 1: Use DNA pooling techniques to identify non-coding region SNPs that are associated with SLE in a European-American (EA) population. Specific Aim 2: Conduct multiple fine-mapping experiments of the regions identified in Aim 1 using at least two genotyping platforms to characterize the individual associated SNPs. Specific Aim 3: Conduct expression and structural analysis on a "risk" and "non-risk" haplotype identified in Aim 2 as part of functional studies.