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

Abstract

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.

Canine noninflammatory alopecia: An approach to its classification and a diagnostic aid

“…7b). 99 Recurrent alopecia affecting the face only has been described in the Cane Corso and in several Dogues de Bordeaux. 139 Similar to typical recurrent flank alopecia, the existence of a strong breed predilections implies a hereditary component.…”

“…14,60,81,82,99,134,148 Thus, it may be speculated that a polygenic trait and other nongenetic factors, such as diet and an altered hormone metabolism, are involved in the pathogenesis. 20,31,60,99 Histological features in most of those conditions are insufficiently described. If dogs were biopsied, only a small number of affected dogs have been investigated and different pathologists were involved.…”

“…Histologic findings in cases of atypical recurrent flank alopecia are comparable to those observed in typical recurrent flank alopecia. 99…”

“…85,149 Canine follicular dysplasia that develops after birth is associated with abnormal reconstitution of the inferior portion of the HF or the HS and may present histologically as a cycling defect. 12,24,31,39,48,78,84,99,128,140 In the later cases, the histology is often comparable to acquired HC disturbances, and only the knowledge about the breed affected, the age of onset, and the exclusion of endocrinopathies allows for a definite diagnosis. The fact that hormonal imbalances have been identified in HF dysplasias that develop postnatally suggests a genetic predisposition and explains their histological similarity to acquired HC disorders caused by endocrinopathies.…”

“…Due to the clear breed disposition, an underlying hereditary cause is likely, although no causative genes have been identified in the disorders that have been genetically evaluated. 14,60,81,82,99,134,148 Thus, it may be speculated that a polygenic trait and other nongenetic factors, such as diet and an altered hormone metabolism, are involved in the pathogenesis. 20,31,60,99 Histological features in most of those conditions are insufficiently described.…”