Investigation of the Genetics of Asthma

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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===========================================