Complex traits, like the susceptibility to common diseases, are controlled by numerous genomic regions which individual effect is generally weak. Collaborative Cross (CC) is a panel of recombinant inbred mice derived from randomized breeding of eight laboratory inbred strains combining high genetic diversity (captures 90% of the genetic variation known in the mouse genome) with the advantage of inbred mouse strains. This panel has previously been studied for a wide range of traits and can be used for high-resolution association mapping. NK cells in the anti-tumor response are well described, however, the impact of other Innate lymphoid cells (ILCs) subsets in cancer immunology remains less defined. This project aims at identifying novel genetic traits that regulate the anti-tumor activities of NK cells and other ILC using Collaborative Cross (CC) mice. We have identified CC strains that diverge in their anti-tumor immune responses and are characterizing the molecular mechanisms responsible for these differences. However, host genetics and the gut microbiome can both influence immune phenotypes. The genetic background, in a controlled environment, can accounts for a substantial fraction of abundance of most common microbiota. Whether host genetic variation shapes the gut microbiome and interacts with it to affect host immune phenotype is unclear. Toward this end, we profiled gut microbiota using 16s rRNA gene sequencing in a panel of diverse inbred strains of CC mice. Using SNP-based approach with a linear mixed model, we will estimated the heritability of microbiota composition. Ultimately, these diverse genetic traits may lead to the development of novel therapies for cancer.
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