The development of asthma requires exposure to inciting agents such as allergens, environmental pollutants and respiratory infections, as well as the presence of endogenous host or genetic factors. Because of significant interrelationships, the understanding of the genetics of asthma involves the investigation of the genetics of bronchial hyperresponsiveness and allergy. These studies will delineate mechanisms that are important in the pathogenesis and therapy of asthma. While both genetic and environmental factors and their interactions are felt to be important, their precise role is not fully understood. Family studies of the genetics of asthma will be performed utilizing several different populations: local Maryland families (Caucasian and Black) and Hispanic families from New Mexico. Families are being ascertained through an asthmatic proband with a sibling with asthma. All of the children and parents will be tested for bronchial hyperresponsivesness and allergy, and DNA samples will be obtained. Families will be extended into larger pedigrees whenever possible. Segregation analysis will be performed whenever possible to determine the most likely mode of inheritance. However, the primary goal of this proposal is a genome search using highly polymorphic DNA markers to map major genes for bronchial hyperresponsiveness and asthma. Since allergy is commonly associated with asthma, another goal of this proposal is to identify major genes for atopic allergy by linkage with the same set of polymorphic markers. Allergic factors including skin test reactivity to common allergens, serum total and specific IgE levels will be studies. When a linkage is detected, candidate genes related to inflammation, allergy or asthma that have been physically mapped to that chromosomal region will be studied.
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