Differential Gene Expression Associated with Idiopathic Epilepsy in Belgian Shepherd Dogs

Idiopathic epilepsy (IE) disproportionately affects Belgian shepherd dogs and although genomic risk markers have been identified previously in the breed, causative variants have not been described.

The current study analyzed differences in whole blood RNA expression associated with IE and with a previously identified IE risk haplotype on canine chromosome (CFA) 14 using a transcriptomics RNA-seq approach.

MFSD2A and a likely pseudogene of RPL19, both of which are genes implicated in seizure activity, were upregulated in dogs with IE. Genes in the interferon signaling pathway were downregulated in Belgian shepherds with IE. The CFA14 risk haplotype was associated with upregulation of CLIC1, ACE2, and PIGN and downregulation of EPDR1, all known to be involved with epilepsy or the Wnt/β-catenin signaling pathway.

These results highlight the value of assessing gene expression in canine IE research to uncover genomic contributory factors.