209: Towards the identification novel regulators for Th1 differentiation by computational genetics

2013 
T helper (Th) cells play critical functions in response to infectious, allergic, and autoimmune diseases. Upon exposure to an infectious agent or stimulus, different types of Th responses are observed, which influence disease outcome, with differences in responses in different inbred mouse strains as well. To investigate the genetic factors that contribute to such differential immune responses, we have integrated computational genetic analysis and transcriptomic data to identify novel elements involved in Th1 differentiation. We determined the phenotypic profiles of in vitro differentiated Th1 cells from 16 inbred mouse strains by measuring the RNA and protein level of the Th1 signature cytokine (IFN©) at six time points. Then, according to the phenotypic ranking of 16 inbred strains, we performed a haplotype-based computational genetic analysis. At all time points, we observed strong and significant inter-strain differences, which suggested that the observed variations were due to genetic differences, and we identified ∼1075 genes ( p + T cells, ∼80 genes had a significantly change in expression (FC > 2, P
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