Grant: Operating Grant - PA: Institute of Genetics (Bridge Funding)

Asthma is complex respiratory and immune disease. The analysis of the control of the inflammation induced by allergens which result in asthma have demonstrated major genetic effects underlying susceptibility or resistance to asthma. Limited success in identification of genes regulating asthma is not only due to its inherent genetic complexity where disease severity is controlled by several interacting gene products but it is also due to a very limited amount of genetic models suitable for simultaneous mapping of multiple regions underlying a complex trait disease. We have initiated studies aimed at the genetic dissection of susceptibility to asthma using a unique mouse model of asthma allowing mapping chromosomal regions responsible for complex trait disease. Specifically, we have employed in our studies a set of 35 different strains of mice in combination with genechip analysis and demonstrated that this approach provides a powerful tool for finding the genes responsible for diseases such as asthma. We have identified several regions on the chromosomes of the mouse containing genes with a high probability of being relevant to the asthma. The proposed studies delineate our strategy in prioritizing candidate regions and finding genes located in these chromosomal regions which are of importance in asthma diagnostics, severity and progression. We anticipate that the proposed studies will provide us a better understanding the mechanism underlying allergic asthma and will enable the identification of new treatments and targets for new drugs.