Hair of the Dog: Identification of a Cis-Regulatory Module Predicted to Influence Canine Coat Composition

Each domestic dog breed is characterized by a strict set of physical and behavioral characteristics by which breed members are judged and rewarded in conformation shows. One defining feature of particular interest is the coat, which is comprised of either a double- or single-layer of hair. The top coat contains coarse guard hairs and a softer undercoat, similar to that observed in wolves and assumed to be the ancestral state. The undercoat is absent in single-coated breeds which is assumed to be the derived state. We leveraged single nucleotide polymorphism (SNP) array and whole genome sequence (WGS) data to perform genome-wide association studies (GWAS), identifying a locus on chromosome (CFA) 28 which is strongly associated with coat number. Using WGS data, we identified a locus of 18.4 kilobases containing 62 significant variants within the intron of a long noncoding ribonucleic acid (lncRNA) upstream of ADRB1. Multiple lines of evidence highlight the locus as a potential cis-regulatory module. Specifically, two variants are found at high frequency in single-coated dogs and are rare in wolves, and both are predicted to affect transcription factor (TF) binding. This report is among the first to exploit WGS data for both GWAS and variant mapping to identify a breed-defining trait.