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The MexTAg Collaborative Cross: Understanding Genetic Modifiers in Mesothelioma
This is the final progress report for award CA170299. In the last 12 months we have completed all aims as initially intended. In summary we generated, and asbestos exposed over 2500 CC-MexTAg mice, representing 72 genetically distinct groups. Our analysis demonstrated significant variation in disease phenotype, with a 3-fold change in median survival and disease latency between groups, indicating that host genetics does impact asbestos related disease development. We discovered a variety of qualitative trait loci (QTL) for each of 5 traits (phenotypes) assessed and identified candidate genes and regulatory elements associated with each QTL. These data were used to interrogate human mesothelioma datasets, which enabled the identification of human homologues of the candidate genes and their association with mesothelioma development in patient cohorts. We have identified a number of genes that act either individually or in concert to promote or ameliorate mesothelioma development. The role of these genes in mesothelioma pathobiology remains to be fully investigated and this will be the focus of our ongoing and future work.
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