PBMC Treatment Significantly Changes Gene Expression Regulation in Horses

Expression quantitative trait loci (eQTLs) are context dependent, and therefore change between tissues, cell types, and after cell treatment. In addition, SNP positions and RNAseq counts must be updated after assembly of new reference genome sequences. Therefore, we remapped eQTLs with Matrix eQTL using the previously generated and publicly available data from four contexts of peripheral blood mononuclear cells (PBMCs) from European Warmblood horses to the EquCab3.0 reference genome, and used a linear mixed model in R to identify eQTLs with significantly different gene expression regulation in treated PBMCs when compared to no treatment (baseline). We found no evidence that SNPs associated with significant changes in gene expression between MCK and a treatment in PBMCs caused strong opposing regulatory effects. We identified canonical pathways with a significant number of genes in PBMCs with altered gene expression regulation when treated with lipopolysaccharides (LPS) and hay-dust extract (HDE). Significant pathways included RhoA signaling in LPS, as well as histamine degradation, cholesterol biosynthesis, Fc{gamma}RIIB signaling, and others in HDE. Our results support previous research indicating that pathways altered between baseline and treatment of PBMCs in horses with LPS or HDE affect inflammatory responses through RhoA, B-cell signaling, IL-4 and IFN-{gamma}, and histamine.