DESCRIPTION: Acute anterior uveitis (AAU) describes an inflammation of the anterior uveal tract of the eye. Sudden onset, unilateral, acute, anterior uveitis is the most common form of uveitis. It is the phenotype of uveitis that is associated with HLA-B27 and the spondyloarthritic diseases, such as ankylosing spondylitis and reactive arthritis. However, this form of uveitis may also occur in patients with no other systemic inflammatory diseases. Clinical observations clearly indicate that AAU can be familial. We hypothesize that the genetic susceptibility to AAU is multigenic and that in the context of spondyloarthritis, it will be possible to define the contributions of uveitis-specific genetic mutations. This is a competitive renewal of a study to recruit families with more than one member affected with AAU into a genetic data and DNA bank for the purposes of conducting a genome-wide scan using affected sibling pair linkage analysis methods. During the initial funding period, a genome-wide scan was completed. A locus was identified with strong linkage to AAU, but not to ankylosing spondylitis - i.e. what appears to be a bonafide AAU-specific genetic signal. The aims of this proposal are as follows: Specific Aim 1: To expand the database and DNA bank of families with AAU and repeat the genome-wide scan with a larger cohort. Even though one uveitis-specific locus has been found, a larger cohort will be a more robust test of the hypothesis that multiple genes contribute to the genetic predisposition to AAU. Specific Aim 2: To identify candidate genes within the locus identified for susceptibility to AAU by performing functional and positional screening techniques. Specific Aim 3: To identify specific candidate gene mutations by using SNP marker analysis, by comparative DNA sequencing and by denaturing HPLC analysis.