Identification of genetic variants associated with ear length in drop-eared dogs.

External ear size varies dramatically across animals, in part because of its role in thermoregulation: small ears conserve heat, while large ears dissipate heat. Genetic factors influencing ear size are known in several domesticated species but remain unexplored in dogs. We used whole-genome sequences aligned to canFam4 to perform an across-breed genome-wide association study (GWAS) for drop ear length. We identified a significant locus on canine chromosome (CFA) 10, intergenic to MSRB3 and HMGA2. The position of the lead variant (chr10:8,612,500, P = 1.85 × 10- 17) is evolutionarily conserved and, in humans, interacts with an MSRB3 enhancer. Given that this locus governs ear carriage in dogs, which was uniform in our cohort, we conducted a GWAS using prick- and drop-eared breeds to disentangle genetic determinants of ear size and carriage. Our results indicate that two independent variants on CFA10 are associated with ear carriage, but only a recombinant haplotype containing both derived alleles results in drop ears. The allele for ear size arose on the recombinant haplotype and this tri-allelic combination predominates in breeds having the largest drop ears. Conversely, breeds having the ancestral haplotype have small, erect ears. Our findings suggest that each derived variant may act independently to increase ear size, which in turn influences ear carriage.