GENETIC ANALYSIS OF JUVENILE IDIOPATHIC ARTHRITIS

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。 假设：编码T细胞调节分子的基因的遗传变异有助于幼年类风湿关节炎（JRA）易感性、发病机制和治疗结果的变化。 具体目标1。分析编码参与T细胞调节的配体-受体对的基因的遗传多样性。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。 随后将使用单个SNP和单倍型进行关联和连锁研究。 具体目标2。检测特定目标1中鉴定的遗传变异与幼年型类风湿性关节炎（JRA）易感性和/或JRA可变表达率之间的关联和连锁。 这些分析将在3个研究人群中进行：（1）来自辛辛那提的JRA登记处的140个患有JRA的受累同胞对（ASP）及其父母的队列，该登记处由国家关节炎、肌肉骨骼和皮肤疾病研究所（NIAMS）赞助，（2）500个患有JRA的单胎患者及其父母（三人组）的队列，（3）从山间各州儿童风湿性疾病数据库中700多例JRA先证者中确定的三重病例。

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 juvenile rheumatoid arthritis (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.