Compliance between clinical and genetic diagnosis of choroidal hypoplasia in 103 Norwegian Border Collie puppies.

OBJECTIVE: To describe the frequency of the nonhomologous end-joining factor 1 (NHEJ1) mutation and the compliance between clinical and genetic diagnosis of choroidal hypoplasia (CH) in a group of Norwegian Border Collies. ANIMALS STUDIED: Border collie puppies in the age from 5 to 8 weeks. MATERIAL AND METHODS: Puppies included in the study had a complete ophthalmological examination. All findings were recorded, and an ECVO scheme form was issued for each puppy. DNA samples were achieved from buccal swabs. Genetic typing was performed for the 7.8-kb deletion in the gene encoding NHEJ1. Dogs with none, one, or two copies of the mutated allele were classified as free, carriers, and affected, respectively. RESULTS: 103 Border Collie puppies from 16 litters, 52 females and 51 males, were included in the study. Ages ranged from 5.1 to 8.9 weeks. One puppy had clinical findings consistent with CH and optic nerve coloboma compatible with the diagnosis Collie Eye Anomaly (CEA). Findings on ophthalmological examination of the remaining puppies were within normal limits. On genetic testing, 85 puppies were clear of the mutation in the NHEJ1 gene, 17 puppies were carriers, and one puppy was genetically affected. CONCLUSIONS: A good compliance between the clinical diagnosis and the genetic test results was found in all of the puppies examined. The allele frequency of the mutation was 6.3%.

Cataracts in the Norwegian Buhund-current prevalence and characteristics.

OBJECTIVE: To evaluate prevalence and characteristics of cataracts in the Norwegian Buhund breed 20 years after high reported prevalence of especially pulverulent nuclear cataracts (PNCs). ANIMALS STUDIED: Two hundred and fifty Norwegian Buhund dogs in Norway, Sweden, and Denmark (117 males and 133 females) with previously unknown eye health status were included. Forty-five dogs had multiple examinations (two to six times over a 6-year period). Median age was 4.4 years [0.2-15.2] at first examination and 5.3 years [0.2-15.2] at last examination. PROCEDURES: All dogs underwent regular screening for inherited eye diseases. RESULTS: At the last observation of each dog, 52.4% were affected by PNC, categorized as minimal (33 of 250 dogs; 13.2%), mild (31 dogs; 12.4%), moderate (38 dogs; 15.2%), or pronounced (29 dogs; 11.6%). Moderate or pronounced changes were only seen in older dogs, and progressive changes were identified in some of the re-examined dogs. Some dogs, free of lenticular changes at early examinations, were affected by PNC at re-examinations. The odds for finding PNC increased with dog's age up to approximately 8 years. Presumably inherited cataracts other than PNC were found in 53 dogs (21.2%) with cortical (17.6%) and posterior polar (6.4%) locations as the most common ones. CONCLUSIONS: The high prevalence of PNC in the breed reported 20 years ago persists. PNCs are not always visible in young dogs, and the rate of progression varies. The prevalence of other types of cataract is also high, but cataracts rarely cause loss of vision in this breed.

Genomic analysis and prediction of genomic values for distichiasis in Staffordshire bull terriers.

BACKGROUND: Distichiasis is a condition characterized by aberrant hairs along the eyelid margins. The symptoms are usually mild but can lead to ulcerations and lesions of the cornea in severe cases. It is the most frequently noted ocular disorder in Norwegian Staffordshire bull terriers (SBT), with a prevalence above 18% in the adult population. A complex inheritance is assumed, but there is sparse knowledge about the genetic background of distichiasis in dogs. We have performed a genome-wide association study of distichiasis in SBT and used genomic data in an attempt to predict genomic values for the disorder. RESULTS: We identified four genetic regions on CFA1, CFA18, CFA32 and CFA34 using a mixed linear model association analysis and a Bayesian mixed model analysis. Genomic values were predicted using GBLUP and a Bayesian approach, BayesR. The genomic prediction showed that the 1/4 of dogs with predicted values most likely to acquire distichiasis had a 3.9 -4.0 times higher risk of developing distichiasis compared to the quarter (1/4) of dogs least likely to acquire the disease. There was no significant difference between the two methods used. CONCLUSION: Four genomic regions associated with distichiasis were discovered in the association analysis, suggesting that distichiasis in SBT is a complex trait involving numerous loci. The four associated regions need to be confirmed in an independent sample. We also used all 95 K SNPs for genomic prediction and showed that genomic prediction can be a helpful tool in selective breeding schemes at breed level aiming at reducing the prevalence of distichiasis in SBTs in the future, even if the predictive value of single dogs may be low.

Distichiasis is a condition where abnormal hairs grow along the margin of the eyelids. It's common in Staffordshire bull terriers and can cause eye problems of variable severity. The abnormal eye hairs can be found during an eye inspection performed by a veterinarian.We performed a genome-wide association analysis and identified four genomic areas associated with the condition. But more genes may be involved in causing the disease.We have used genomic data to predict genomic values. Genomic values can be used to predict the total load of disease-associated alleles. Genomic prediction would therefore be helpful at the breed level, similar to pedigree-based breeding values, to reduce the prevalence of dogs with distichiasis, even if the low accuracy to predict phenotypes in individual dogs may be a challenge. More research is needed to confirm these findings and see if genomic prediction could be a helpful tool within dog breeding in the future.

Heritability estimates of distichiasis in Staffordshire bull terriers using pedigrees and genome-wide SNP data.

BACKGROUND: Distichiasis is the most frequently recorded eye disorder in the Norwegian Staffordshire bull terrier (SBT). The condition is often mild but can, in severe cases, lead to pain and blindness. The current study's main purpose was to estimate the heritability based on pedigree information as well as single nucleotide polymorphisms (SNPs) to evaluate whether it is realistic to reduce the frequency by systematic breeding. The majority of the dogs had only one examination as a young puppy. To evaluate whether this early screening gave a reliable representation of the disease burden in the population, we compared the diagnosis in puppies and adult dogs. RESULTS: Our material consisted of data from 4177 dogs with an overall prevalence of distichiasis of 8.38% (CI 7.56-9.26). The prevalence in puppies examined around eight weeks of age was significantly lower than in dogs examined after 52 weeks (2.87%, CI 2.29-3.54 versus 18.72%, CI 16.71-20.87). The heritability was estimated in dogs examined after 52 weeks. We used both pedigree (1391 dogs) and genotype (498 dogs) information for the estimates. The pedigree-based heritability was ~ 0.22 (on the underlying scale ~ 0.48), while the genomic-based heritability (on the underlying scale) was ~ 0.47, and ~ 0.37 when excluding close relatives with equal affection status. CONCLUSIONS: Screening for distichiasis in puppies before eight weeks of age is not sufficient to give an accurate estimate of the prevalence, and an additional examination after one year is recommended. The heritability of distichiasis is medium to high, showing that it should be possible to reduce the prevalence by selective breeding.

Cryptococcus gattii chorioretinitis in a ferret.

Bilateral exudative chorioretinitis was diagnosed in an 18-month-old male neutered ferret (Mustela putorius furo) with a generalized Cryptococcus gattii infection confirmed by PCR. The animal was referred to the Ophthalmology Service of the Autonomous University of Barcelona (VTH-UAB) for acute onset blindness. Complete ophthalmic examination revealed absent menace response and dazzle reflex in both eyes (OU), as well as subretinal edema located in the tapetal fundus. At that time, the clinical ophthalmologic diagnosis was bilateral exudative chorioretinitis. Treatment with prednisone (0.5 mg/kg PO q24 h) was instituted in addition to the ongoing treatment with fluconazole (10 mg/kg PO q24 h). The following rechecks revealed secondary cataracts with subsequent lens subluxation and panretinal degeneration OU. Despite being blind and the poor prognosis of disseminate cryptococcosis, the patient remained active and in good body condition during 6 months after the initial diagnosis. At that time, the ferret showed ataxia, incontinence, and generalized pain. A magnetic resonance imaging study revealed a mass affecting the spine. The owners declined further investigations and the ferret was humanely euthanized. The postmortem histopathology confirmed the initial diagnosis of cryptococcosis and the presence of intraretinal Cryptococcus spp. To the authors' knowledge, this is the first report of Cryptococcus spp. induced exudative chorioretinitis in a ferret.

A slowly progressive retinopathy in the Shetland Sheepdog.

OBJECTIVE: To describe a slowly progressive retinopathy (SPR) in Shetland Sheepdogs. Animals Forty adult Shetlands Sheepdogs with ophthalmoscopic signs of SPR and six normal Shetland Sheepdogs were included in the study. PROCEDURE: Ophthalmic examination including slit-lamp biomicroscopy and ophthalmoscopy was performed in all dogs. Electroretinograms and obstacle course-test were performed in 13 affected and 6 normal dogs. The SPR dogs were subdivided into two groups according to their dark-adapted b-wave amplitudes. SPR1-dogs had ophthalmoscopic signs of SPR, but normal dark-adapted b-wave amplitudes. Dogs with both ophthalmoscopic signs and subnormal, dark-adapted b-wave amplitudes were assigned to group SPR2. Eyes from two SPR2 dogs were obtained for microscopic examination. RESULTS: The ophthalmoscopic changes included bilateral, symmetrical, greyish discoloration in the peripheral tapetal fundus with normal or marginally attenuated vessels. Repeated examination showed that the ophthalmoscopic changes slowly spread across the central parts of the tapetal fundus, but did not progress to obvious neuroretinal thinning presenting as tapetal hyper-reflectivity. The dogs did not appear seriously visually impaired. SPR2 showed significantly reduced b-wave amplitudes throughout dark-adaptation. Microscopy showed thinning of the outer nuclear layer and abnormal appearance of rod and cone outer segments. Testing for the progressive rod-cone degeneration ( prcd )-mutation in three dogs with SPR was negative. CONCLUSION: Slowly progressive retinopathy is a generalized rod-cone degeneration that on ophthalmoscopy looks similar to early stages of progressive retinal atrophy. The ophthalmoscopic findings are slowly progressive without tapetal hyper-reflectivity. Visual impairment is not obvious and the electroretinogram is more subtly altered than in progressive retinal atrophy. The etiology remains unclear. SPR is not caused by the prcd-mutation.

A study of candidate genes for day blindness in the standard wire haired dachshund.

BACKGROUND: A genetic study was performed to identify candidate genes associated with day blindness in the standard wire haired dachshund. Based on a literature review of diseases in dogs and human with phenotypes similar to day blindness, ten genes were selected and evaluated as potential candidate genes associated with day blindness in the breed. RESULTS: Three of the genes, CNGB3, CNGA3 and GNAT2, involved in cone degeneration and seven genes and loci, ABCA4, RDH5, CORD8, CORD9, RPGRIP1, GUCY2D and CRX, reported to be involved in cone-rod dystrophies were studied. Polymorphic markers at each of the candidate loci were studied in a family with 36 informative offspring. The study revealed a high frequency of recombinations between the candidate marker alleles and the disease. CONCLUSION: Since all of the markers were at the exact position of the candidate loci, and several recombinations were detected for each of the loci, all ten genes were excluded as causal for this canine, early onset cone-rod dystrophy. The described markers may, however, be useful to screen other canine resource families segregating eye diseases for association to the ten genes.

Uveal myxoid leiomyosarcoma in a horse.

A uveal leiomyosarcoma of a horse is reported. There are few published reports of intraocular tumors in horses. Intraocular tumors challenge animal welfare by causing uveitis, glaucoma, and loss of vision. Knowledge regarding treatment of intraocular tumors with globe preservation is sparse, and further investigations on this topic are required.

Listeria monocytogenes associated kerato-conjunctivitis in four horses in Norway.

Listeria monocytogenes has been reported to cause various infectious diseases in both humans and animals. More rarely, ocular infections have been reported. To our knowledge, only two cases of Listeria keratitis have been described in horses. We report kerato-conjunctivitis in four Norwegian horses associated with L. monocytogenes. Clinically, all cases were presented with recurrent unilateral kerato-conjunctivitis. L. monocytogenes bacteria were isolated from swab samples from all cases, and cytology carried out in 3 cases was indicative of L. monocytogenes infection. The present report describes the first known cases in which L. monocytogenes has been isolated from keratitic lesions in horses in Norway. A potential risk factor may be feeding of silage or haylage, but other sources of infection cannot be ruled out. The phenotypic features including antimicrobial susceptibility and serotype of the isolates are described. Laboratory detection of L. monocytogenes demands extra caution since only low numbers of bacteria were detected in the eye-swabs, probably due to the low volume of sample material and the intracellular niche of the bacterium. A general poor response to treatment in all these cases indicates that clinicians should pay extra attention to intensity and duration of treatment if L. monocytogenes is identified in connection with equine kerato-conjunctivitis.

A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund.

Cone-rod dystrophy is a retinal degenerative disorder occurring naturally in man and dog. Here we identify a novel gene for early-onset cone-rod dystrophy in the wire-haired dachshund. For the first time, we use genome-wide association-based Sibling Transmission Disequilibrium Test (sibTDT) analysis of only 13 discordant sib-pairs to identify a single significantly associated 6.5-Mb region (PrawTDT = 4.8 x 10(-5), PgenomeTDT = 6 x 10(-4)) on canine chromosome 5, containing more than 70 genes. Segregation studies using microsatellites in the candidate region including additional meiosis supported the sibTDT analysis but could not further reduce the area. Candidate gene resequencing identified a 180-bp deletion in exon/intron 5 of NPHP4 (nephronophthisis 4, also known as nephroretinin). RT-PCR analysis of NPHP4 in cases and controls showed exon skipping of exon 5, resulting in a truncated protein that retains the binding domain interacting with nephronophthisis 1 (also known as nephrocystin-1) in the kidney but lacks the domain interacting with RPGRIP1 in retina. We suggest that this deletion in the canine NPHP4 gene is the cause of cone-rod dystrophy in the standard wire-haired dachshund. In humans, mutations in NPHP4 have been associated with simultaneous eye and kidney disease. Here we describe the first naturally occurring mutation in NPHP4 without additional kidney disease. Further studies will permit elucidation of the complex molecular mechanism of this retinopathy and the development of potential therapies.