Comparative systematic genetics for cardiovascular disease gene identification

心血管疾病基因鉴定的比较系统遗传学

• 批准号: 7156592
• 负责人: Joel S. Bader
• 金额: $ 18.27万
• 依托单位: FABRIC GENOMICS INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156592
• 关键词: Caenorhabditis elegans; Drosophilidae; Saccharomyces cerevisiae; animal data; arthropod genetics; biochemical evolution; bioengineering /biomedical engineering; cardiovascular disorder risk; computer program /software; computer system design /evaluation; functional /structural genomics; fungal genetics; gene deletion mutation; gene expression; genetic models; genetic polymorphism; genetic screening; genetic susceptibility; genotype; human data; linkage mapping; molecular biology information system; phenotype; zebrafish

DESCRIPTION (provided by applicant): This proposal will lead to identification of gene variants that increase the risk of developing cardiovascular disease. The underlying hypothesis is that systematic genetics conducted in model organisms enables the identification of disease-specific gene modules. This hypothesis will be tested in Phase I through the following Aims: (1) Create a database of phenotypes observed in systematic genetic screens conducted in yeast, worm, fly, zebrafish, and other model organisms. (2) Develop and apply data mining algorithms to identify modules of genes whose deletion or silencing phentoypes show similar patterns across model organisms. (3) Identify modules that are enriched for genes with known variants relevant to cardiovascular disease. Other genes in these modules will then be candidate genes for variants conferring cardiovascular disease risk or can be used to improve priors for whole-genome association tests. In Phase II, variants of candidate genes will be genotyped across a cardiovascular patient population with the goal of identifying genetic markers to assist in diagnosis and treatment of cardiovascular disease. If successful, this proposal will lead to genetic tests that will improve the clinical treatment of patients at risk for cardiovascular disease. The comparative systematic genetics platform developed will be broadly applicable to identifying gene modules relevant to other human diseases and will extend to systematic genetics data collected for a growing set of model organisms.

描述（由申请人提供）：该提案将导致鉴定出增加患心血管疾病风险的基因变体。基本的假设是在模型生物中进行的系统遗传学可以鉴定疾病特异性基因模块。该假设将通过以下目的在第I阶段进行检验：（1）在酵母，蠕虫，苍蝇，斑马鱼和其他模型生物体中进行的系统遗传筛选中观察到的表型数据库。 （2）开发和应用数据挖掘算法以识别删除或沉默的基因模块的模块，这些基因在模型生物体之间显示出相似的模式。 （3）确定对与心血管疾病相关的已知变异基因富含基因的模块。然后，这些模块中的其他基因将是赋予心血管疾病风险的变体的候选基因，或用于改善全基因组关联测试的先验。在第二阶段，将在心血管患者人群中进行基因分型的候选基因变体，目的是鉴定遗传标记以帮助诊断和治疗心血管疾病。如果成功，该建议将导致基因检测，以改善患心血管疾病风险的患者的临床治疗。开发的比较系统遗传学平台将广泛适用于识别与其他人类疾病相关的基因模块，并将扩展到为不断增长的一组模型生物所收集的系统遗传学数据。