Investigation of the Genetics of Asthma

超出所提供的空间。哮喘是一种常见的慢性肺部炎症性疾病，受遗传和环境因素的影响。作为CSGA的一部分，我们使用临床表型来寻找影响哮喘易感性的基因。许多暗示性的染色体区域已经被发现，虽然没有明确的联系已经建立。我们假设哮喘是一种复杂的疾病，包括遗传和病理生理学，包括特应性、气道高反应性和炎症。我们拥有由大型多代家族（明尼苏达家族）组成的独特资源，通过这些资源，我们可以假设更大的遗传同质性，基于主要生理要素改善表型，并提供更多的力量，使用易患哮喘的多组分表型进行基因搜索。这项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，并确定导致其发展的基因。这些目标将在以下具体目标中实现。1.建立数量性状易感哮喘，并应用统计聚类分析这些性状之间的明尼苏达州的家庭。2.使用多点连锁分析确定负责这些多组分表型的染色体区域。3.通过基因精细定位和DNA序列分析，确定这些定位区域中负责哮喘易感成分的候选基因。这项研究将利用通过CSGA和一种新的方法已经收集的广泛的家庭数据来确定哮喘易感基因。这将是识别可用于预测性遗传分析和开发针对这一常见医学问题的药物靶点的基因的第一步。性能现场=

EXCEED THE SPACE PROVIDED. Asthma is a 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 pathophysiology, including the elements of atopy, airways hyperreactivity and inflammation. We have a unique resource comprised of large, multi-generation families (Minnesota Families), with which we can assume greater genetic homogeneity, improve phenotypes based upon the major physiological elements and provide more power to focus gene searches using multi-component phenotypes predisposing 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 identify the genes responsible 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. PERFORMANCE SITE ========================================Section End===========================================