# Initial Genome-Wide Case–Control Study for Genetic Background of Retinal Dysplasia in Czechoslovakian Wolfdog

## TL;DR

This study identifies a genetic region linked to retinal dysplasia in Czechoslovakian Wolfdogs, a breed previously thought to be free of such eye issues.

## Contribution

The study reports a genome-wide association finding for retinal dysplasia in Czechoslovakian Wolfdogs, highlighting the CYP27A1 gene region.

## Key findings

- A genome-wide association study found a significant link between retinal dysplasia and a locus on chromosome CFA37.
- The strongest signal was in the first intron of the CYP27A1 gene, which is involved in vitamin D metabolism.
- The CFA37 region contains other genes previously linked to ocular development and disease.

## Abstract

Retinal dysplasia is a complex canine eye disease that is determined by a combination of genetic and non-genetic risk factors. The genetic basis of retinal dysplasia in specific canine breeds remains incompletely understood. While the Czechoslovakian Wolfdog is generally known for being free of significant eye problems, our research has shown that multifocal retinal dysplasia can occur in this breed. A clinical study of 117 Czechoslovakian Wolfdogs found six samples with symptoms of multifocal retinal dysplasia. A genome-wide case–control association study of 36 adult dogs identified association on chromosome CFA37, specifically in the first intron of the CYP27A1 gene. The region of this gene is very interesting because other genes linked to ocular diseases in animal models are localized in this locus. It suggests the possibility of multiple genes contributing to the multiple retinal dysplasia phenotype in Czechoslovakian Wolfdogs.

Retinal dysplasia is a genetically heterogeneous ocular disorder in dogs, characterized by abnormal retinal development, resulting in a range of visual impairments from mild to complete blindness. The objective of this study was to investigate the prevalence and genetic basis of retinal dysplasia in the Czechoslovakian Wolfdog breed. An ophthalmic examination was conducted on a cohort of 117 Czechoslovakian Wolfdogs, which revealed a prevalence of multifocal retinal dysplasia of 5.13%. A genome-wide case–control association study was conducted on a subset of 36 adult dogs to explore the underlying genetic architecture of multifocal retinal dysplasia in this breed. The GWAS identified a suggestive association with a locus on canine chromosome CFA37. The strongest association signal for SNP marker BICF2G630130992 (p = 1.29 × 10−6) was identified in the first intron of the CYP27A1 gene, which encodes a cytochrome P450 enzyme involved in vitamin D metabolism and potentially retinal function. The region of CFA37 contains several other genes that have been previously implicated in ocular development and disease. Further studies utilizing next-generation sequencing and functional analyses are required to validate these findings, identify the causative variants, and fully elucidate the genetic architecture of retinal dysplasia in this breed.