Genomic and Transcriptomic Characterization of Atypical Recurrent Flank Alopecia in the Cesky Fousek

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.

Automated summary

Non-inflammatory alopecia is a common skin problem in dogs that affects the integrity of their coat and appearance. This study focused on the Cesky Fousek breed, which frequently experiences atypical recurrent flank alopecia (aRFA). The genetic cause of aRFA is unknown, so this study aimed to identify the associated variants using histological, genomic, and transcriptomic data. Through a genome-wide association study (GWAS) and comparison of gene expression patterns, several candidate genes were identified, suggesting a polygenic basis for aRFA. These genes are involved in metabolic pathways related to collagen formation, muscle structure/contraction, lipid metabolism, and the immune system.