Validation of a Chromosome 14 Risk Haplotype for Idiopathic Epilepsy in the Belgian Shepherd Dog Found to Be Associated with an Insertion in the <i>RAPGEF5</i> Gene

Abstract

An idiopathic epilepsy (IE) risk haplotype on canine chromosome (CFA) 14 has been reported to interact with the CFA37 common risk haplotype in the Belgian shepherd (BS). Additional IE cases and control dogs were genotyped for the risk haplotypes to validate these previous findings. In the new cohort, the interaction between the two regions significantly elevated IE risk. When the haplotypes were analyzed individually, particular haplotypes on both CFA14 (ACTG) and 37 (GG) were associated with elevated IE risk, though only the CFA37 AA was significantly associated (p RAPGEF5 gene, which is adjacent to the CFA14 risk haplotype. RAPGEF5 is involved in the Wnt-β-catenin signaling pathway that is crucial for normal brain function. Although this risk variant does not fully predict the likelihood of a BS developing IE, the association with a variant in a candidate gene may provide insight into the genetic control of canine IE.

Keywords

• dog
• idiopathic epilepsy
• <i>RAPGEF5</i>
• risk haplotype