Analysis of Genetic Susceptibility to Anterior Uveitis

前葡萄膜炎遗传易感性分析

• 批准号: 7255641
• 负责人: TAMMY M MARTIN
• 金额: $ 47.95万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7255641
• 关键词: Acute; Affect; American; Americas; Ankylosing spondylitis; Anterior; Anterior uveitis; Australia; Canada; Candidate Disease Gene; Chromosomes; Clinic; Clinical; DNA Databases; DNA Library; DNA Sequence; Databases; Disease; Enrollment; Eye; Family; Funding; Gene Mutation; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genetic Predisposition to Disease; Genome Scan; Germany; HLA Antigens; Health Sciences; High Pressure Liquid Chromatography; Immune response; Individual; Inflammation; Inflammatory; Major Histocompatibility Complex; Maps; Medical center; Methods; Mutation; Ophthalmologist; Oregon; Participant; Pathogenesis; Patients; Phenotype; Polymorphism Analysis; Predisposition; Process; Progress Reports; Purpose; Reactive Arthritis; Recruitment Activity; Research Personnel; Running; Scanning; Screening procedure; Severities; Siblings; Signal Transduction; Single Nucleotide Polymorphism; Societies; Source; Specialist; Spondylitis; Susceptibility Gene; Techniques; Technology; Testing; Tissues; United States Department of Veterans Affairs; Universities; Uvea; Uveitis; arthropathies; base; case control; cohort; comparative; defined contribution; density; genetic linkage analysis; genome wide association study; interest; member; programs

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.

描述：急性前葡萄膜炎（AAU）描述了眼睛前卵巢的炎症。突然发作，单侧，急性，前葡萄膜炎是葡萄膜炎的最常见形式。葡萄膜炎的表型与HLA-B27和脊椎关节炎疾病有关，例如强直性脊柱炎和反应性关节炎。但是，这种形式的葡萄膜炎也可能发生在没有其他全身性炎症性疾病的患者中。临床观察结果清楚地表明AAU可能是家族性的。我们假设对AAU的遗传敏感性是多基因的，并且在脊椎关节炎的背景下，可以定义葡萄膜炎特异性遗传突变的贡献。这是一项研究的竞争性更新，该研究旨在招募一个以上AAU影响遗传数据和DNA库的家庭，目的是使用受影响的同级兄弟姐妹对链接分析方法进行全基因组扫描。在最初的资金期间，完成了全基因组扫描。一个基因座被鉴定出与AAU有很强的联系，但不能与强直性脊柱炎 - 即，似乎是真正的AAA AAU特异性遗传信号。该提议的目的如下： 具体目标1：用AAU扩展数据库和DNA库，并使用较大的队列重复全基因组扫描。即使发现一个葡萄膜炎特异性的基因座，较大的队列将对多个基因有助于AAU的遗传倾向的假设进行更强大的检验。特定目的2：通过执行功能和位置筛选技术，确定识别为对AAU敏感的候选基因。特定目的3：通过使用SNP标记分析，比较DNA测序和定性HPLC分析来鉴定特定的候选基因突变。