DOI: 10.5061/dryad.r7sqv9sqs
title: Deletion in <em>CACNA1F</em> gene causes X-linked progressive retinal atrophy in English Cocker Spaniel dogs

description: 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.
description: 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.
description: # Deletion in *CACNA1F* gene causes X-linked progressive retinal atrophy
 in English Cocker Spaniel dogs Dataset DOI:
 [10.5061/dryad.r7sqv9sqs](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.