INVESTIGATION OF THE GENETICS OF ASTHMA

哮喘的遗传学研究

• 批准号: 7605974
• 负责人: Malcolm Nolan Blumenthal
• 金额: $ 1.42万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605974
• 关键词: Air; Allergens; Area; Asthma; Blood; Blood specimen; Candidate Disease Gene; Chronic; Cluster Analysis; Complex; Computer Retrieval of Information on Scientific Projects Database; Condition; DNA; DNA Sequence Analysis; Data; Development; Disease; Drug Delivery Systems; Elements; Environmental Risk Factor; Exhalation; Family; Family Study; Funding; Generations; Genes; Genetic; Goals; Grant; Health; Hypersensitivity; Hypersensitivity skin testing; IgE; Inflammation; Inflammatory; Institution; Investigation; Lung diseases; Maps; Measures; Medical; Minnesota; Nitric Oxide; Phenotype; Predisposition; Protocols documentation; Pulmonary function tests; Questionnaires; Research; Research Personnel; Resources; Source; Susceptibility Gene; Testing; United States National Institutes of Health; airway hyperresponsiveness; atopy; clinical phenotype; genetic analysis; genetic linkage analysis; improved; member; methacholine; novel strategies; programs; respiratory; trait

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma is common, chronic inflammatory disorder of the lungs influenced by genetic and environmental factors. As part of the CSGA, we have searched for genes that influence asthma susceptibility using clinical phenotypes. Numerous suggestive chromosomal areas have been found, though no clear linkages have been established. We hypothesize that asthma is a complex condition both with respect to its inheritance and phathophysiology, including the elements of atopy, airways hyperreactivity adn inflammation. We have a unique resource comprised of large, multi-generation families (Minnesota Families), with which we can assume greater genetic homogeneity, improve phenotypes using multi-component phenotypespredisposing to the development of asthma. The overall goals of this proposal are to determine if asthma is a unique disease or a cluster of distinct disorders and identfy the genes rresponsible for their development. These goals will be pursued in the following specific aims. 1. Establish quantitative traits predisposing to asthma, and apply statistical cluster analyses to these traits among the Minnesota Families., 2. Identify the chromosomal regions responsible for these multi-component phenotypes, using multipoint linkage analyses. 3. Identify candidate genes in these mapped areas responsible for the components predisposing to asthma by using genetic fine mapping and DNA sequence analysis. This study will utilize the extensive data already collected on families through the CSGA and a novel approach to identify asthma susceptibility genes. This will be the first step in the identification of genes that can be used for predictive genetic analyses and development of drug targets for this common medical problem. Subjects alreday ascertained for asthma under these prior protocols will be invited to come to GCRC to have nitric oxide(NO) analysis of their exhaled air and to donate a 30 cc blood sample for cellular studies. We will ask the GCRC to measure the subject's vital signs and to draw this blood, but the No analysis will be performed in GCRC by a memeber of the Allergy & Asthma Program staff. Additional members form our previously studied families and other new subjects will be asked to undergo ascertainment, including completion of a respiratory health questionnaire, pulmonary function testing (methacholine challenge and / or broncho reversibility), skin testing to 14 common allergens, and a blood draw 940cc) for IgE levels and DNA isolation in addition to NO analysis and donating blood (30 cc) for cellular studies. Again, GCRC will be asked to measure vital signs and to draw the blood sample. All other testing will be performed in the GCRC by a member of the Allergy & Asthma Program staff.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 哮喘是一种常见的慢性肺部炎症性疾病，受遗传和环境因素影响。作为 CSGA 的一部分，我们利用临床表型寻找影响哮喘易感性的基因。已经发现了许多暗示性的染色体区域，但尚未建立明确的联系。我们假设哮喘在遗传和病理生理学方面都是一种复杂的疾病，包括特应性、气道高反应性和炎症的要素。我们拥有由大型多代家庭（明尼苏达家庭）组成的独特资源，利用这些资源，我们可以假设更大的遗传同质性，并利用易导致哮喘发展的多成分表型来改善表型。该提案的总体目标是确定哮喘是一种独特的疾病还是一组不同的疾病，并确定导致其发生的基因。这些目标将通过以下具体目标来实现。 1. 建立易患哮喘的数量性状，并对明尼苏达家系中的这些性状进行统计聚类分析。 2. 使用多点连锁分析确定导致这些多成分表型的染色体区域。 3. 通过使用遗传精细定位和 DNA 序列分析，识别这些映射区域中负责诱发哮喘的成分的候选基因。这项研究将利用通过 CSGA 收集的大量家庭数据和一种识别哮喘易感基因的新方法。这将是鉴定可用于预测遗传分析和针对这一常见医学问题开发药物靶点的基因的第一步。 根据这些先前方案已确定患有哮喘的受试者将被邀请来 GCRC 对呼出的空气进行一氧化氮 (NO) 分析，并捐献 30 cc 血液样本用于细胞研究。我们将要求 GCRC 测量受试者的生命体征并抽取血液，但“否”分析将由过敏和哮喘项目工作人员在 GCRC 中进行。我们之前研究的家庭的其他成员和其他新受试者将被要求接受确定，包括完成呼吸健康问卷、肺功能测试（乙酰甲胆碱激发和/或支气管可逆性）、14 种常见过敏原的皮肤测试、抽血（940cc）以检测 IgE 水平和 DNA 分离，此外还进行 NO 分析和献血（30cc）用于细胞研究。 GCRC 将再次被要求测量生命体征并抽取血样。所有其他测试将由过敏和哮喘项目工作人员在 GCRC 中进行。