BB Principal Investigator/Program Director (Last, first, middle): Huang, Shau-Ku, PhD DESCRIPTION. State the application's broad, long-term objectives and specific aims, making reference to the health relatedness of the project. Describe concisely the research design and methods for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This description is meant to serve as a succinct and accurate description of the proposed work when separated from the application. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. D O N O T E X C E E D T H E S PA C E P R OVI D E D. The genetic basis of IgE responsiveness leading to the expression of atopic diseases remains elusive. This is due, in part, to the multi-genetic nature of the disease involving a complex array of molecular genetic networks and environmental factors. Recent consistent evidence has suggested that chromosome 5q, 1 lq and 12q regions contain susceptibility gene(s) regulating IgE responsiveness and/or asthma. The overall objective of our continuing effort is, therefore, to determine the nature of the susceptibility gene(s) and its functional relevance. In this new grant application, we will target specifically the candidate genes associated with the regulation of Th2 cell responses on these three critical chromosomal regions, for which the evidence of association with and linkage to atopic phenotypes have been significant and consistent. We will continue to focus on the analysis of well-defined and previously studied populations. Systematic analysis allelic polymorphisms within these candidate gene loci and their functional correlates will be pursued, with initial emphasis on recently identified sequence variants. Multiple statistics will be used to increase the power for linkage/association detection, including Transmission Disequilibrium Test (TDT) and haplotype analysis. This proposal presents a continuing effort built upon our past accomplishment, with the aim being to identify susceptibility gene(s) regulating IgE responsiveness and/or asthma. It is anticipated that the accomplishment of these studies will greatly facilitate the efforts to uncover the genetic basis of IgE responsiveness and atopic diseases. aERFORMANCE SITE(S) (organization, city, state) Johns Hopkins University, Johns Hopkins Asthma & Allergy Center, Baltimore, MD KEY PERSONNEL ========================================Section End===========================================
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