Gene-environment interactions in asthma in mice and humans

National Human Genome Research Institute

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Abstract

We first established a mouse model of dust mite-induced asthma that recapitulates the key features of human asthma, namely airway hyper-responsiveness, inflammation, and mucus production. We then applied this model to a newly established population of mice known as the Collaborative Cross (CC). This population captures the more than 95% of the genetic diversity present in all inbred strains of mice. This genetic and resulting phenotypic diversity greatly enhances the power to identify quantitative trait loci (QTL). We phenotyped more than 150 mice and genotyped the mice using a high-density Affymetrix array. Using these data, we identified QTL for airway inflammation, specifically the numbers of macrophages (Chromosome (Chr) 17), eosinophils (Chr 11), and neutrophils (Chr 2) in lung lavage fluid. We also identified a QTL for serum IgG2b.We are currently refining these QTL to identify candidate genes using conditional correlation and additional genome sequence data. We plan to test the role of human homologs of the candidate genes we identify in the mouse in human population-based studies of allergic asthma through collaborations that are already underway with Drs. Cookson and Postma.