DOI: 10.5061/dryad.3tx95x6n6
title: Data from: Two genes, one culprit - a functional candidate validation of a <em>SPATA7</em> deletion in dogs with day blindness/retinal degeneration

description: Inherited retinal diseases (IRDs) are a diverse group of disorders that
 share common vision deficit ranging from early onset blindness to
 seInherited retinal diseases (IRDs) are a diverse group of disorders that
 share common vision deficit ranging from early onset blindness to severe
 and progressive blindness occurring in later years. We report a form of
 cone-rod dystrophy with early onset day vision loss in the Standard
 poodle. Through GWAS and homozygosity mapping, a large deletion on
 CFA8:g.(60,022,583_60,040,453del) was found, which removes 3’ portions of
 two different genes, PTPN21 and SPATA7, presenting a challenge for
 assessing the actual causative gene in a multi-gene large deletion. All
 affected dogs were homozygous for the mutant allele, which segregated
 perfectly with the phenotype within the breed. The variant was also absent
 fromand was also absent in more than control canine structural variants
 database(dog10k). While the role of SPATA7 for retinal disease has been
 established in human patients and genetically engineered mice, the role of
 PTPN21 in retina is unclear even though it is expressed in rod and cone
 photoreceptors. Expression of truncated transcripts for both genes was
 detected in skin fibroblasts from the cases. Retinal RNA analysis showed
 that PTPN21 splicing suggests that in mutant dogs at least one unmodified
 transcript is present. Ptpn21-/- knockout mice did not have an ocular
 phenotype, and opsin-specific IHC detected no cone or rod abnormalities in
 the mice suggesting that PTPN21 loss has none to minimal contributory role
 towards the retinal phenotype in the affected dogs. The SPATA7 deletion
 (XM_038674407.1:c.1,301-2,070del, p.Arg387_Asp595del) affects the coding
 region of the transcript, reducing the predicted protein from 595 to 386
 AA . Ultrastructure expansion microscopy (U-ExM) enabled the detection of
 a distinct SPATA7 signal around the transition zone of the primary cilium
 in WT canine-skin fibroblasts, which was absent in that of affected dogs.
 We propose that SPATA7 deficiency is the main cause of the condition and
 propose this disease as a model for the SPATA7-related form of cone-rod
 dystrophy in human. Our work shows an example of functional refinement of
 a multi-gene deletion variant using a multi-technique approach.
description: SNPdata: genotype data Type from 170k and 220k CanineHD array
 (<em>Illumina</em>). DNA was extracted from blood. Processed:
 Neogen. SP03 NovaSeq6000 paired-end reads (2x100 bp)
 whole genome sequencing (as for company instructions). The PCR-free
 library was prepared as follows. Libraries of 300 bp insert size were
 prepared, and Illumina NovaSeq6000 paired-end reads (2 × 100 bp) were
 collected. Fastq files were generated using Casava.
description: Pood_RET - GWAS plink data in tped format. \ Pood_RET.tfam - tfam
 file PLINK\ Pood_Ret.tped - tped file PLINK Phenotypes in PLINK files:
 SP003, SP004, SP005, SP006, SP007, SP012 are cases. Rest are controls
 (unaffected by the retinal condition). \ SP003 - whole-genome sequenced
 case - Standard Poodle with inherited retinal condition. SP003_R1.fastq.gz
 - pair-ended canine 30x WGS reads, right\ SP003_R2.fastq.gz - pair-ended
 canine 30x WGS reads, left