ABCB1 Frameshift Deletion in Skye Terriers With Potential Pharmacogenetic Relevance

ABSTRACT Ivermectin‐associated neurotoxicity is a potentially life‐threatening condition caused by disruption of the ABCB1 encoded P‐glycoprotein drug transporter in certain dog breeds. Skye terriers are considered at increased risk of ivermectin toxicity despite the absence of an identified molecular cause. We searched the Dog10K variant dataset for ABCB1 variants potentially underlying ivermectin sensitivity in Skye terriers and screened an independent cohort of 27 dogs to confirm sequence variants. A 1‐bp frameshift deletion predicted to cause loss of function in ABCB1 was identified in two of three Skye terriers in the Dog10K dataset and was absent from all 1869 non‐Skye‐terrier genomes. The variant had an allele frequency of 16.7% in the independent Skye terrier cohort. This is the first reported ABCB1 variant in Skye terriers and represents a plausible candidate genetic basis for the anecdotally observed ivermectin sensitivity in the breed.