Deletion in CACNA1F gene causes X-linked progressive retinal atrophy in English Cocker Spaniel dogs
Data files
Feb 10, 2026 version files 139.24 GB
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ECS_CACN.map
6.30 MB
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ECS_CACN.ped
7.95 MB
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ECS04.R1.fastq.gz
24.58 GB
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ECS04.R2.fastq.gz
25.38 GB
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ECS05_R1.fastq.gz
13.69 GB
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ECS05_R2.fastq.gz
14.33 GB
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ECS06_R1.fastq.gz
13.44 GB
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ECS06_R2.fastq.gz
14.20 GB
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ECS54_R1.fastq.gz
16.40 GB
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ECS54_R2.fastq.gz
17.20 GB
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README.md
2.47 KB
Abstract
Progressive retinal atrophy (PRA) was diagnosed in four related male English Cocker Spaniels (ECS) between the ages of 3 and 4 years. All affected dogs were born to clinically healthy parents that had tested negative for known PRA-causing variants. Pedigree analysis revealed that the mothers of the affected dogs were paternal half-siblings, and their father had been reported as visually impaired, suggesting an X-linked recessive mode of inheritance. To identify the underlying genetic cause, we performed homozygosity mapping, identifying six candidate regions, and whole-genome sequencing. A single high-impact coding variant—a 1-bp deletion in exon 36 of the CACNA1F gene on X chromosome—was identified. This variant is predicted to cause a frameshift and premature stop codon and was found in all affected males and heterozygous in their mothers, while being absent in unaffected control dogs. A specifically designed PCR test was developed and applied to a broader cohort of 92 related and unrelated ECS dogs, confirming the segregation of this variant. This study identified a novel CACNA1F variant responsible for an X-linked form of PRA in the ECS. Given that CACNA1F is already associated with retinal disorders in other mammals, including humans, this finding adds to its relevance across species. Development and implementation of specific genetic screening tests are recommended to inform breeding strategies and prevent further dissemination of this deleterious mutation within the breed.
Dataset DOI: 10.5061/dryad.r7sqv9sqs
Description of the data and file structure
WGS of affected cases and unaffected parents. TRIO: Case (male, ECS04) with unaffected mother (ECS05) and unaffected father (ECS06) ECS54: additional case
ECS04_R1.fastq.gz
ECS04_R1.fastq.gz
ECS05_R2.fastq.gz
ECS05_R1.fastq.gz
ECS06_R1.fastq.gz
ECS06_R2.fastq.gz
ECS54: additional case
ECS54.R1.fastq.gz
ECS54.R2.fastq.gz
Plink format illumina SNP chip, 220k, DNA extracted with BACC2 from blood. Genotyped as for standard protocols.
ECS_CACN.map
ECS_CACN.ped
Files and variables
File: ECS04.R1.fastq.gz
Description: Affected case, R1 reads, Illumina NovaSeq6000 (paired-end reads, 2 × 100 bp)
File: ECS04.R2.fastq.gz
Description: Affected case, R2 reads, Illumina NovaSeq6000 (paired-end reads, 2 × 100 bp)
File: ECS54_R1.fastq.gz
Description: Affected case, R2 reads, Illumina NovaSeq6000 (paired-end reads, 2 × 100 bp) :
File: ECS54_R2.fastq.gz
Description: Affected case, R2 reads, Illumina NovaSeq6000 (paired-end reads, 2 × 100 bp)
File: ECS05_R1.fastq.gz
Description: Unaffected mother of ECS04, R1 reads, Illumina NovaSeq6000 (paired-end reads, 2 × 100 bp)
File: ECS05_R2.fastq.gz
Description: Unaffected mother of ECS04, R2 reads, Illumina NovaSeq6000 (paired-end reads, 2 × 100 bp)
File: ECS06_R1.fastq.gz
Description: Unaffected father of ECS04, R1 reads, Illumina NovaSeq6000 (paired-end reads, 2 × 100 bp)
File: ECS06_R2.fastq.gz
Description: Unaffected father of ECS04 , R2 reads, Illumina NovaSeq6000 (paired-end reads, 2 × 100 bp)
PLINK files - SNP mapping
ECS04, ECS54 - affected
ECS05, ECS06, ECS07, ECS37, ECS36, ECS55, ECS48 - unaffected
File: ECS_CACN.map
Description: Plink file of genotyped 2 cases and normal relatives, .map file, plink format
File: ECS_CACN.ped
Description: Plink file of genotyped 2 cases and normal relatives, .ped file, plink format
Code/software
fastq must be processed with a mapper (usually bwa, processed with samtools, and visualized with a viewer like Integrative genome viewer). This is standard for this type of pipeline and described in the paper's methods.
plink files are readable by any plink version.
WGS + homozygosity mapping revealed the candidate variant, which was then checked for segregation in canine atabases (2000+ dogs) and in a selected population of English Cocker Spaniels of European and US descent.