T-CELL REGULATORY MOLECULES IN JUVENILE RHEUMATOID ARTHRITIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。假设：编码t细胞调控分子的基因的遗传变异导致了JRA易感性、发病机制和治疗结果的变化。具体目标分析参与t细胞调控的配体-受体对编码基因的遗传多样性。将对来自非洲、亚洲和欧洲的110个个体的18个基因进行重新测序。这些数据将用于识别单核苷酸多态性（snp），推断单倍型，并估计单倍型的进化结构。单个snp和单倍型随后将用于关联和连锁研究。具体目标2。在特定目的1中鉴定的遗传变异与幼年类风湿性关节炎（JRA）易感性和/或JRA的可变表达性之间的关联和联系的测试。这些分析将在3个研究人群中进行：(1)来自美国国家关节炎、肌肉骨骼和皮肤疾病研究所（NIAMS）赞助的辛辛那提JRA登记处的140对患有JRA的兄弟姐妹（asp）及其父母的队列，(2)500名患有JRA的单胞胎及其父母（三人组）的队列，以及(3)从山间州儿童风湿病数据库中700多名患有JRA的先证中确定的三人组。

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. Hypothesis: Genetic variation in genes encoding T-cell regulatory molecules contributes to variation in JRA susceptibility, pathogenesis and treatment outcomes. Specific Aim 1. Analyze genetic diversity in genes encoding ligand-receptor pairs involved in T-cell regulation. Eighteen genes will be re-sequenced in a population of 110 individuals from Africa, Asia, and Europe. These data will be used to identify single nucleotide polymorphisms (SNPs), infer haplotypes, and estimate the evolutionary structure of haplotypes. Individual SNPs and haplotypes will subsequently be used for association and linkage studies. Specific Aim 2. Test for association and linkage between genetic variants identified in specific aim 1 and susceptibility to Juvenile rheumatoid arthritis (JRA) and/or variable expressivity of JRA. These analyses will be performed in 3 study populations: (1) a cohort of 140 affected sib-pairs (ASPs) with JRA and their parents from a JRA registry in Cincinnati, sponsored by the National Institute of Arthritis, and Musculoskeletal and Skin diseases (NIAMS), (2) a cohort of 500 singletons with JRA and their parents (trios), and (3) trios ascertained from more than 700 probands with JRA in the Intermountain States Database of Childhood Rheumatic Diseases.