ADMINISTRATIVE/EDUCATION CENTER FOR INNATE IMMUNITY PGA

PGA 先天免疫管理/教育中心

• 批准号: 6294319
• 负责人: SCOTT T WEISS
• 金额: $ 39.97万
• 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 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6294319
• 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.

拟议计划（改编自申请人的摘要） 哮喘、慢性阻塞性肺疾病（COPD）、心肌梗塞 (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）。 这些人的综合医疗保健费用 条件每年大约1000亿美元。 RFA HL 的目标- 99-024 心脏、肺和血液研究的基因组应用正在开发 扩展心脏、肺和血液领域的基因组知识， 将这些知识应用于疾病病理学。 已经有相当多的 对这些病症的疾病机制的理解取得进展， 所有四种都与局部炎症的发展有关 过程。 很明显，细胞和细胞因子是 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 (UA) 科学中心医学系 布莱根妇女医院 (BWH) 的生物信息学项目 波士顿儿童医院（瑞士）开发人类变异发现 以非同源免疫及其广泛关系为主题的方案 心脏、肺和血液疾病。 亚利桑那州/BWH PGA 将提供 科学界对基因变异进行了全面筛查 最有可能影响风险的先天免疫基因的子集 上述四种疾病。 调查人员还将进行 初步评估这些变体与四种病毒的关联 正在研究的表型，以指导这些领域的研究人员远离变异 相关性和对那些表现出有前途的人的可能性很低 影响四种疾病中任何一种的功能和流行病学证据 表型。 为了实现这一广泛目标，研究人员有 具体目标如下：（1）筛选已知的100个基因的多态性 与先天免疫反应直接或间接相关； (2) 基因分型 西班牙裔、非西班牙裔白人和非裔美国人的样本 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，以确定最有可能的 SNP 参与哮喘、慢性阻塞性肺疾病的测定 疾病、心肌梗塞和深静脉血栓形成； (4) 传播 有关种族特异性和表型特异性分布的信息 完成后 60 天内在网站上研究多态性 基因分型研究； (5) 制定培训计划 结识具有不同知识和经验的个人 现代遗传技术在高通量测序和 基因分型；遗传研究设计、数据处理和数据分析 流行病学；以及群体遗传学中的伦理问题。