Genetic insights into canine flank alopecia in Rhodesian ridgebacks: identifying candidate genes

Canine flank alopecia (CFA) is a recurrent, seasonal, non-inflammatory skin disorder of uncertain etiology that affects several breeds, including Rhodesian ridgebacks. While endocrine and environmental influences have been suggested, the genetic background remains unclear. This study aimed to identify candidate genes associated with CFA in Rhodesian ridgebacks using a genome-wide approach. Low-pass whole-genome sequencing with imputation was performed on 48 Rhodesian ridgebacks (24 cases, 24 controls), followed by genome-wide association analyses and evaluation of protein-coding variants. Filtering for variants with predicted functional impact revealed variants in SPTB, SYNE2, EPB41L1, and DPY19L1, which are involved in cytoskeletal function, cell adhesion, neural signaling, and pathways critical for hair follicle cycling, such as Wnt, BMP, MAPK, Notch, and Hedgehog signaling. Our findings demonstrate that CFA is likely a skin disorder with genetic heterogeneity, where multiple loci and possibly modifier variants influence disease susceptibility, rather than a simple monogenic disorder. These results align with the complex inheritance observed in atypical recurrent flank alopecia, supporting a complex multifactorial etiology involving both genetic and environmental factors. This study provides the first insights into the genetic background of CFA in Rhodesian ridgebacks and highlights candidate genes for further functional investigation. Broader genomic approaches are needed to elucidate the disorder's genetic basis, ultimately guiding CFA-preventative breeding strategies.