Asthma prevalence, morbidity and mortality are higher among Latino Americans on the east coast than on the west coast of the U.S. This is in stark contrast to the near geographic uniformity of asthma morbidity and mortality rates among African Americans and Caucasians in the U.S. The differences in asthma prevalence and severity among Latino Americans on the two coasts may reflect differences in the genetic contributions of Ancestral Native American, Spanish and African populations to the Latino population on the east coast (predominantly Puerto Rican) and west coast (predominantly Mexican). To determine whether identifiable genetic factors are associated with asthma and severe asthma among Mexican Americans, the largest U.S. Hispanic group, we will recruit Mexican American asthmatic subjects (probands) and their biologic parents (n=600) from California during a 1 year period. Probands will undergo formal phenotypic characterization. We will assemble a repository of DNA and plasma from the probands and their parents. We will identify novel single nucleotide plymorphisms (SNPs) among candidate genes at loci where there is evidence to suggest linkage to asthma in previous studies of other populations. We will determine whether novel SNPs and SNPs known to be associated with asthma in other populations are associated with asthma in Mexican Americans. We will compare the results generated from this repository to similar ongoing studies in Puerto Rican asthmatic families. The creation of a repository of DNA from well-characterized Mexican American asthmatics will enable future analysis of other genes identified in other studies. The results of this work may have important implications for the diagnosis, treatment and prognosis of asthma not only in Mexican Americans, but in other populations as well. The proposed research project is one component of a career development plan designed to prepare the applicant to lead an independent program applying novel advances in genomics to improving the diagnosis and treatment of asthma in medically underserved populations. The training component of this application includes oversight from an experienced pulmonary physician-scientist (Dr. Dean Sheppard), with a strong track-record in training successful pulmonary academicians, formal mentoring from a multidisciplinary scientific advisory committee, all collaborators from GALA, and advanced didactic training in clinical research design and genetic association studies. This proposal?s focus is consistent with the goal established by Healthy People 2010, to reduce disparities in health among different populations.