RNA-Seq identifies differential gene expression associated with risk-genotype for Rhodococcus equi pneumonia in horses

Rhodococcus equi is an intracellular bacterium that affects young foals and immuno-compromised individuals causing severe pneumonia. Currently, the genetic mechanisms which confer susceptibility and or resistance to R. equi are not fully understood. Previously, using a SNP-based genome-wide association study, we identified a region on equine chromosome 26 associated with clinical pneumonia. To better characterize this region and understand the relationship of the SNPs associated with disease, we performed RNA-Seq on 12 horses representing the 3 allelic states of the SNP identified. Differential expression analyses identified differentially expressed genes in the innate immune response pathway when comparing homozygous A allele horses with the AB and BB horses. Isoform analyses of the RNA-Seq data predicted multiple transcripts with evidence of differential expression to exist at the TRPM2 locus. This finding is consistent with previously demonstrated work in human cell lines in which isoform specific expression of TRPM2 was critical to cell viability. This work demonstrates that SNPs in TRPM2 are associated with differences in gene expression, suggesting that modulation of expression of this innate immune gene contributes to susceptibility to R. equi pneumonia. Overall design: Analysis of RNA expression derived from 3 genotypes

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