Non-inflammatory alopecia is a frequent skin problem in dogs, causing damaged coat integrity and compromised appearance of affected individuals. In this study, we examined the Cesky Fousek breed, which displays atypical recurrent flank alopecia (aRFA) at a high frequency. This type of alopecia can be quite severe and is characterized by seasonal episodes of well demarcated alopecic areas without hyperpigmentation. The genetic component responsible for aRFA remains unknown. Thus, here we aimed to identify variants involved in aRFA using a combination of histological, genomic, and transcriptomic data. We showed that aRFA is histologically similar to recurrent flank alopecia, characterized by a lack of anagen hair follicles and the presence of severely shortened telogen or kenogen hair follicles. We performed a genome-wide association study (GWAS) using 216 dogs phenotyped for aRFA and identified associations on chromosomes 19, 8, 30, 36, and 21, highlighting 144 candidate genes, which suggests a polygenic basis for aRFA. By comparing the skin cell transcription pattern of six aRFA and five control dogs, we identified 236 strongly differentially expressed genes (DEGs). We showed that the GWAS genes associated with aRFA are often predicted to interact with DEGs, suggesting their joint contribution to the development of the disease. Together, these genes affect four major metabolic pathways connected to aRFA: collagen formation, muscle structure/contraction, lipid metabolism, and the immune system.

Department of Animal Science and Food Processing Faculty of Tropical AgriSciences Czech University of Life Sciences Prague 16500 Prague Czech Republic

Department of Biomedical Sciences College of Veterinary Medicine Cornell University Ithaca NY 14853 USA

Department of Botany Faculty of Science Charles University 12800 Prague Czech Republic

DermFocus University of Bern 3012 Bern Switzerland

Institute of Animal Pathology Vetsuisse Faculty University of Bern 3012 Bern Switzerland

Institute of Genetics Vetsuisse Faculty University of Bern 3012 Bern Switzerland

Molecular and Biomedical Sciences and School of Marine Sciences University of Maine Orono ME 04469 USA

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