BIOINFORMATICS CENTER FOR INNATE IMMUNITY PGA

先天免疫生物信息学中心 PGA

• 批准号: 6637327
• 负责人: ROSS LAZARUS
• 金额: $ 64.05万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6637327
• 关键词: African American; Hispanic Americans; Internet; asthma; caucasian American; chronic obstructive pulmonary disease; clinical research; cooperative study; genetic polymorphism; genetic techniques; human population genetics; human subject; immunogenetics; informatics; myocardial infarction; phenotype; racial /ethnic difference; training; venous thrombosis

PROPOSED PROGRAM (Adapted from the Applicant's Abstract) Asthma, chronic obstructive pulmonary disease (COPD), myocardial infarction (MI), and deep venous thrombosis (DVT) are among the most common diseases of the lung, heart, and blood (ref). The combined health care costs for these conditions approximate 100 billion dollars per year. The goal of the RFA HL- 99-024 Genomic Applications for Heart, Lung, and Blood Research is to develop and expand genomic knowledge within the heart, lung, and blood community and apply that knowledge to disease pathobiology. There have been considerable advances in the understanding of the disease mechanisms for these conditions, and all four are associated with the development of a local inflammatory process. It has become apparent that cells and cytokines that are part of the innate immune system control the early phases of this process of airway, lung, and blood vessel inflammation. The proposal builds on the strengths of three institutions: the Respiratory Sciences Center at the University of Arizona (UA), the Department of Medicine at Brigham & Women's Hospital (BWH), and the Bioinformatics Program at Children's Hospital in Boston (CH), to develop a human variation discovery program on the theme of non-cognate immunity and its broad relationship to heart, lung, and blood diseases. The Arizona/BWH PGA will provide the scientific community with a complete screen of the genetic variants in a subset of innate immunity genes that are most likely to influence the risk for the four diseases noted above. The investigators will also perform a preliminary assessment of the association of these variants with the four phenotypes under study, to guide researchers in these areas away from variants with low likelihood of being relevant and toward those showing promising functional and epidemiologic evidence of influencing any of the four disease phenotypes. To accomplish this broad goal, the investigators have the following specific aims: (1) To screen for polymorphisms 100 genes known to be directly or indirectly related to the innate immune response; (2) To genotype a sample of individuals of Hispanic, non-Hispanic White, and African American ethnicity for all the newly discovered polymorphisms; (3) To perform association studies and phylogenetic analysis to identify SNPs most likely to be involved in the determination of asthma, chronic obstructive pulmonary disease, myocardial infarction, and deep venous thrombosis; (4) To disseminate the information on ethnic-specific and phenotype-specific distribution of the polymorphisms under study on a web site within 60 days of the completion of the genotyping studies; (5) To develop a training program that will allow individuals with different knowledge and experience to become acquainted with modern genetic techniques in the fields of high throughput sequencing and genotyping; study design, data handling and data analysis in genetic epidemiology; and ethical issues in population genetics.

建议摘要（改编自申请人摘要） 哮喘、慢性阻塞性肺疾病（COPD）、心肌梗死 (MI)和深静脉血栓形成（DVT）是最常见的疾病之一， 肺、心脏和血液（参考）。 这些人的综合医疗费用 每年大约1000亿美元。 RFA HL的目标- 99-024基因组在心脏、肺和血液研究中的应用 扩大心脏、肺和血液社区的基因组知识， 将这些知识应用于疾病病理学。 相关的环境有很多 对这些病症的疾病机制的理解的进展， 这四种都与局部炎症的发展有关 过程 已经变得明显的是，细胞和细胞因子，是一部分， 先天免疫系统控制气道，肺， 和血管炎症。 该提案建立在三个机构的优势之上： 亚利桑那大学医学系科学中心 布里格姆妇女医院（BWH）的生物信息学项目， 波士顿儿童医院（CH），开发人类变异发现 关于非同源豁免及其与国际法的广泛关系的专题方案 心脏病、肺病和血液病。 亚利桑那州/BWH PGA将提供 科学界对遗传变异进行了全面的筛查， 先天免疫基因的子集，最有可能影响的风险， 上述四种疾病。 调查人员还将执行一项 初步评估这些变异与四种 表型研究，以指导研究人员在这些领域远离变异 相关性较低，并且倾向于那些表现出有希望的人 影响四种疾病中任何一种的功能和流行病学证据 表型 为了实现这一广泛的目标，研究人员有 以下具体目的：（1）筛选多态性100个已知的基因， 与先天免疫反应直接或间接相关;（2）基因型 西班牙裔、非西班牙裔白色和非洲裔美国人的样本 所有新发现的多态性的种族;（3）执行 关联研究和系统发育分析，以确定最有可能 参与确定哮喘、慢性阻塞性肺疾病 疾病，心肌梗死和深静脉血栓形成;（4）传播 关于种族特异性和表型特异性分布的信息 在网站上的多态性研究完成后60天内， 基因分型研究;（5）制定培训计划， 有不同知识和经验的人去熟悉 高通量测序领域的现代遗传技术， 基因分型;遗传学研究设计、数据处理和数据分析 流行病学;和人口遗传学中的伦理问题。