Fine Mapping of Genes for Age-Related Maculopathy

年龄相关性黄斑病基因的精细定位

基本信息

批准号：
7266936
负责人：
SUDHA K IYENGAR
金额：
$ 62.78万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-23 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7266936
关键词：
10q26 12q13 12q23 15q 15q21 16p12 20q13 2p21 4p16 5q34 9p24 9q31 Affect Age related macular degeneration Age-Years Appendix Blindness Candidate Disease Gene Case-Control Studies Castor Chromosome Mapping Chromosomes Clinic Communities Data Data Set Databases Developed Countries Developing Countries Disease Disease Progression Doctor of Philosophy Equilibrium Evaluation Eye Eye diseases Family Family member Functional disorder Gene Mutation Genes Genetic Genome Scan Genotype Goals Individual Lead Life Linkage Disequilibrium Macular degeneration Manuscripts Maps Methods Molecular Mutation Numbers Participant Pathogenesis Persons Population Predisposition Process Reporting Research Design Research Personnel Retina Retinal Risk SNP genotyping Sampling Sampling Studies Scanning Signal Transduction Significance Level Single Nucleotide Polymorphism Staging Susceptibility Gene Testing Universities Validation Western World Wisconsin age related aging population base case control cohort density follow-up gene cloning novel positional cloning programs

项目摘要

DESCRIPTION (provided by applicant): Macular degeneration is a leading cause of blindness in the Western World that affects the aging population. The complexity of the molecular basis of age-related macular degeneration is now beginning to be elucidated with the identification of disease-causing loci through multiple genome scans. This proposal describes a follow-up to two genome scans, one on a community based study (The Beaver Dam Eye Study) and the second in sample obtained from a Retinal Clinic (The Family Age Related Maculopathy Study) conducted by our group. We have evidence of a major locus on chromosome 15q21 (GATA50C03 multipoint P = 1.98 x 10[7]; empirical P < 10[-5]; singlepoint P = 3.6 x 10[-7]) in the Family Age Related Maculopathy Study. This locus was present as a weak linkage signal in our previous ARMD genome scan in the Beaver Dam Eye Study sample (D15S659 multipoint P=0.047), which represents a replication of our results. In the current proposal we will follow up our initial results by fine mapping the region on 15q. We have presented a tiered strategy to perform fine mapping, including validating our results in a sample of cases and controls from the Age-Related Eye Disease Study. We also propose to map other loci that demonstrated positive linkage signals in our genome scan. The cloning of genes for the heritable forms of macular degeneration will increase our understanding of the basic pathogenesis of the disease process. Further, since we propose to examine a case control sample, we will be able to obtain initial estimates of attributable risk due to a particular gene in the population.

描述（由申请人提供）：黄斑变性是影响衰老人口的西方世界失明的主要原因。与年龄相关黄斑变性的分子基础的复杂性现在开始通过通过多种基因组扫描来鉴定引起疾病的基因座的鉴定。该提案描述了两项基因组扫描的后续行动，一项是基于社区的研究（Beaver Dam Eye研究），第二个是从我们小组进行的视网膜诊所（与家庭年龄相关的大量刺激研究）获得的样本中。我们有证据表明，在家庭年龄相关的大斑马病研究中，我们在15q21染色体15q21（GATA50C03多点P = 1.98 x 10 [7];经验P <10 [-5];单点P = 3.6 x 10 [-7]中）。在Beaver Dam Eye研究样本中我们以前的ARMD基因组扫描中，该基因座是作为弱连接信号（D15S659多点P = 0.047）中存在的，这代表了我们结果的复制。在当前的提案中，我们将通过在15q上详细映射该区域来跟进我们的初始结果。我们提出了一个分层的策略进行精细的映射，包括在与年龄相关的眼病研究中的病例和对照样本中验证我们的结果。我们还建议绘制其他在基因组扫描中显示正链信号的基因座。黄斑变性的基因克隆将增加我们对疾病过程基本发病机理的理解。此外，由于我们建议检查一个案例控制样本，因此我们将能够获得由于人群中特定基因而导致的归因风险的初始估计。