GENETIC ANALYSIS OF JUVENILE IDIOPATHIC ARTHRITIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 假设：编码T细胞调节分子的基因的遗传变异导致幼年类风湿性关节炎(JRA)的易感性、发病机制和治疗结果的差异。 具体目的1.分析参与T细胞调节的配体-受体对编码基因的遗传多样性。来自非洲、亚洲和欧洲的110个个体中的18个基因将被重新测序。这些数据将被用来识别单核苷酸多态(SNPs)，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。 特定目的2.特定目的1中确定的基因变异与幼年类风湿性关节炎(JRA)的易感性和/或JRA的可变表达能力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)由国家关节炎和肌肉骨骼及皮肤病研究所赞助的辛辛那提JRA登记中140名受影响的同胞对(ASP)及其父母的队列；(2)500名患有JRA及其父母的单身人群(TRIO)的队列；以及(3)山间各州儿童风湿病数据库中700多名患有JRA的先证者中确定的三人组。

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 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.