GENETIC ANALYSIS OF JUVENILE IDIOPATHIC ARTHRITIS

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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.