Analysis of systematic effects on congenital sensorineural deafness in German Dalmatian dogs

We have analysed the systematic influences, phenotypic colour markers and the additive genetic variation for congenital sensorineural deafness (CSD) in German Dalmatian dogs in order to help elucidate the importance of phenotypic breed characteristics for genetic differences of CSD. Linear animal models using restricted maximum likelihood methods were employed to estimate variance components. Data were obtained from all three German Dalmatian kennel clubs associated with the German Association for Dog Breeding and Husbandry (VDH). CSD was recorded by standardized protocols for brainstem auditory-evoked response (BAER). The material included 1899 German Dalmatian dogs from 354 litters in 169 different kennels. BAER testing results were from the years 1986 to 1999. Pedigree information was available for up to seven generations. The animal model regarded the fixed effects of sex, coat colour, eye colour, presence of patches, litter size, percentage of examined puppies per litter, kennel club, and inbreeding coefficient. The common environment of the litter and kennel as well as the additive genetic effect of the animal were taken into account as randomly distributed effects. The fixed effects of eye colour, percentage of puppies examined per litter and kennel club were significant in the mixed model analysis. A significant proportion of additive genetic variation could be shown despite corrections for phenotypic colour variants. The heritability estimate for CSD in German Dalmatian dogs was h(2)=0.27+/-0.07. The additive genetic correlation of CSD with presence of blue eyes was r(g)=0.53+/-0.41 and with presence of patches r(g)=-0.36+/-0.24. We concluded that additional genes other than those associated with phenotypic colour markers in German Dalmatian dogs significantly contribute to the occurrence of CSD.     

Deafness prevalence and pigmentation and gender associations in dog breeds at risk

Hearing function was tested in dogs from breeds at risk for pigment-associated congenital sensorineural deafness - Dalmatian, English setter (ES), English cocker spaniel (ECS), bull terrier (BT), Australian cattle dog (ACD), whippet, Catahoula leopard dog, and Jack Russell terrier. Deafness prevalence was highest in Dalmatians and lowest in ECS. Phenotype correlation studies were performed in breeds with >100 brainstem auditory evoked responses (BAER) tested subjects. No gender differences were observed. No differences were seen between black- and liver-spotted Dalmatians, among the ES roan colour varieties, among the ECS parti varieties, or among the ACD colour varieties. Blue eyes were positively associated and patches were negatively associated with deafness in the Dalmatian. Blue eyes were also associated with deafness in the ES and ECS. White BT were more likely than coloured BT to be deaf. Having one or more parent's ear deaf was positively associated with deafness in Dalmatians, ES, and ECS.     

Brainstem Auditory-Evoked Potential Assessment of Congenital Deafness in Dalmatians: Associations With Phenotypic Markers

To screen for congenital deafness, brainstem auditory-evoked potential (BAEP) testing was performed on 1031 Dalmatians from three geographically separated areas. Phenotypic marker assessment was done to determine markers possibly associated with deafness. Markers included sex, hair coat color, pigmentation of different areas of skin (eye rims, nose, and ears), presence of a patch, spot size and marking (density of spotting), sire and dam BAEP status, and presence of iris and retinal tapetal pigmentation. Combined data from all test sites showed 8.1% bilateral deafness (N = 83 dogs) and 21.6% unilateral deafness (N = 223), or an overall 29.7% incidence of hearing disorders. Significant (P less than 0.05) associations with deafness for the data from all test sites combined were seen for patch, sire and dam BAEP, iris pigment, and retinal pigment. However, results differed for several of the significant phenotypic markers when analyses were done on the data from the individual test sites; changes from significant to not significant were found. This suggested the existence of multiple populations of deafness patterns, and reinforced the precautionary conclusion that associations of phenotypic markers with deafness are not necessarily functionally significant.     

Gender effects in hearing loss in Dalmatians

Brainstem auditory-evoked-response data were collected from 3101 Dalmatian dogs from 1984 to 1998 at the Veterinary Medicine Teaching Hospital at the University of California, Davis. Also collected were data on eye color and the presence or absence of a color-patch at birth. Our objective was to evaluate the role of gender in hearing loss, including the possibility that the probability of suffering unilateral or bilateral deafness was greater if the dam was hearing impaired than if the sire was hearing impaired.Results of a multiple-trait threshold-model analysis support the commonly held observation that females were more likely to be deaf than males. In addition, females were also more likely to have two blue eyes (a condition associated with an increased prevalence of deafness). However, gender differences in hearing loss were limited to these direct observations. There was no detectable difference in the prevalence of hearing loss between offspring of deaf mothers and the offspring of deaf fathers. Finally, there was no detectable decrease in the prevalence of hearing loss over the years covered in the data set - suggesting that Dalmatian breeders are not yet selecting against hearing problems.     

Prevalence of Deafness in Dogs Heterozygous or Homozygous for the Merle Allele

Background: Deafness in dogs is frequently associated with the pigment genes piebald and merle. Little is known about the prevalence of deafness in dogs carrying the merle allele.
Objective: To determine the prevalence of deafness in dogs heterozygous and homozygous for the merle allele of the mouse Silver pigment locus homolog (SILV) gene.
Animals: One hundred and fifty-three privately owned merle dogs of different breeds and both sexes.
Methods: Hearing was tested by brainstem auditory-evoked response and classified as bilaterally hearing, unilaterally deaf, or bilaterally deaf. DNA from buccal cells was genotyped as either heterozygous or homozygous for the merle allele. Deafness association tests among merle genotype, eye color, and sex were performed by the χ² test.
Results: Deafness prevalence in merles overall was 4.6% unilaterally deaf and 4.6% bilaterally deaf. There was a significant association between hearing status and heterozygous versus homozygous merle genotype. For single merles ( Mm ), 2.7% were unilaterally deaf and 0.9% were bilaterally deaf. For double merles ( MM ), 10% were unilaterally deaf and 15% were bilaterally deaf. There was no significant association with eye color or sex.
Conclusions: Deafness prevalence in merle dogs was greater than that in some dog breeds homozygous for the piebald gene, such as the English Cocker Spaniel, but comparable to, or lower than, that in the Dalmatian and white Bull Terrier. Dogs homozygous for the merle allele were significantly more likely to be deaf than heterozygotes.     

Congenital deafness in Jack Russell terriers: Prevalence and association with phenotype

Congenital hereditary sensorineural deafness is the most common form of deafness in dogs. The objectives of this study were to determine a reliable measure of the prevalence of deafness in Jack Russell terriers, an affected breed, and associations between deafness and phenotypic characteristics. Brainstem auditory evoked response recordings and phenotypic parameters (coat color, coat texture, sex, eye color, sire and dam hearing status) were recorded for 1009 Jack Russell terriers. The prevalence of unilateral and bilateral deafness was 3.57% and 0.50%, respectively, lower by a factor of three to four than in earlier reports based on smaller and closely related kindreds. Significant association with deafness was identified with white coat color and parental hearing status, but not with sex or coat type. Lack of significant sex or coat type associations and the significant association with white coat color are consistent with previous reports. In conclusion the prevalence of deafness in Jack Russell terriers is lower than initially reported. Deafness was associated with white coat color and parental hearing status. The association with parental hearing status supports this form of deafness being a heritable trait in the breed and the association with white coat color supports an inheritance linked to pigmentation genes.     

Prevalence of unilateral and bilateral deafness in border collies and association with phenotype

BACKGROUND: Congenital sensorineural deafness (CSD) occurs in Border Collies, but its prevalence and inheritance are unknown. This study estimated the prevalence of CSD in Border Collies and investigated its association with phenotypic attributes linked to the merle gene, including coat pigmentation and iris color. HYPOTHESIS: Deafness in Border Collies is associated with pigmentation patterns linked to the merle gene. ANIMALS: A total of 2597 Border Collies from the United Kingdom. METHODS: A retrospective study of Border Collies tested, during 1994-2002, by using brainstem auditory evoked responses. Associations between deafness and phenotypic attributes were assessed by using generalized logistic regression. RESULTS: The prevalence of CSD in puppies was estimated as 2.8%. The corresponding rates of unilateral and bilateral CSD were 2.3 and 0.5%, respectively. Adjustment for clustering of hearing status by litter reduced the overall prevalence estimate to 1.6%. There was no association between CSD and sex (P = .2). Deaf Border Collies had higher rates of merle coat pigmentation, blue iris pigment, and excess white on the head than normal hearing Border Collies (all P < .001). The odds of deafness were increased by a factor of 14 for Border Collies with deaf dams, relative to the odds for dogs with normal dams (P = .007), after adjustment for phenotypic attributes. CONCLUSIONS AND CLINICAL IMPORTANCE: Associations between CSD and pigmentation patterns linked to the merle gene were demonstrated for Border Collies. Evidence for an inherited component to CSD in Border Collies supports selective breeding from only tested and normal parents to reduce the prevalence of this disease.     

Further contributions to the genetic aspect of congenital sensorineural deafness in Dalmatians

Sensorineural deafness is a common congenital disorder in Dalmatians and is genetically transmitted. Different modes of inheritance have been proposed and the objective of this study was to study these by segregation analyses using maximum likelihood procedures. Data from 33 complete Dalmatian families were collected and data from 56 single Dalmatians added. This resulted in a total of 575 dogs with 357 known phenotypes. All dogs were clinically evaluated and electrophysiologically tested with brainstem auditory evoked responses.The prevalence of deafness was 16.5% (9.4% unilaterally deaf, 7.1% bilaterally deaf). Females were 4.4% more affected than males but this difference was not significant. Within the same litter, different phenotypic expressions of deafness occurred, which suggested different expressions of the disease. In addition, two data sets were analysed: the first included normal, uni- and bilaterally deaf dogs, the second had normal and deaf Dalmatians. We found that a recessive allele at a single biallelic major locus fitted our data best, although an incomplete penetrance of the recessive homozygotes was observed.     

Brainstem auditory-evoked potential assessment of auditory function and congenital deafness in llamas (Lama glama) and alpacas (L. pacos)

Auditory function of llamas and alpacas was assessed objectively by means of brainstem auditory-evoked response audiometry (BAER) to establish the normal hearing range and to test the hypothesis of a correlation between blue eyes, white coat, and deafness. Sixty-three camelids were available for the study. Thirteen animals had blue irides; 1 animal had 1 blue and 1 pigmented iris. Wave latencies, amplitudes, and interpeak latencies were measured under general anesthetic. Click stimuli (dB [HL]) were delivered by an insert earphone. Four to five positive peaks could be detected; waves I, II, and V were reproducible; wave II appeared infrequently; and wave IV generally merged with wave V to form a complex. Peak latencies decreased and peak amplitudes increased as stimulus intensity increased. A hearing threshold level of 10-20 dB (HL) was proposed as the normal range in llamas and alpacas. None of the animals with pigmentation of coat and iris showed any degree of hearing impairment. Seven of the 10 blue-eyed, pure-white animals were bilaterally deaf and one of them was unilaterally deaf. However, 2 blue-eyed, white animals exhibited normal hearing ability. Three blue-eyed animals with pigmented coat did not show any hearing impairment. All white animals with normal iris pigmentation had normal auditory function; so did the 1 animal with 1 normal and 1 blue iris. The high frequency (78%) of bilaterally deaf animals with pure white coat and blue iris pigmentation supports the hypothesis of a correlation between pigmentation anomalies and congenital deafness in llamas and alpacas.     

Effects of risk factors and prophylactic treatment on primary glaucoma in the dog

Seventy dogs from 26 breeds were admitted with primary glaucoma between January 1979 and December 1983. Compared with mixed-breed dogs, 8 breeds were at higher risk (P less than 0.01) of developing glaucoma: Basset Hound, Beagle, Boston Terrier, Cocker Spaniel, Dalmatian, Miniature Poodle, Norwegian Elkhound, and Siberian Husky. Dogs between the ages of 5 and 10 years were at increased risk (P less than 0.001). There was no predisposition for either eye to be affected first (P greater than 0.55). Females were at twice the risk of males (P less than 0.01). Fourteen dogs had bilateral glaucoma. Among 46 dogs for which the number of months that the second eye remained normal was available, 24 were treated prophylactically and 22 were not treated or had treatment stopped. Prophylactic treatment significantly extended the interval between diagnosis in the first eye and development of glaucoma in the second eye for dogs in predisposed breeds (P less than 0.01). Prophylactic treatment did not make a difference when all breeds were considered (P greater than 0.19), nor did gender affect this interval (P greater than 0.37).     

Use of brain stem auditory-evoked response to evaluate deafness in a group of Dalmatian dogs

A group of 18 adult and 28 six-week-old purebred Dalmatian dogs was tested for hearing by brain stem auditory-evoked responses. Each ear was tested independently. Absence of a response was considered evidence of deafness in that ear. Responses from bilaterally hearing adults and pups and unilaterally hearing dogs were compared with each other and with responses from normally hearing, adult, mixed-breed dogs. Of the 18 adults tested, 5 had normal responses from both ears, 6 were deaf in both ears, and 7 had a response from only one side. Of 28 pups tested, 14 had normal responses from both ears, 9 had a response from only one ear, and 5 were bilaterally deaf. Wave peak latencies from all ears that responded were within normal limits, except that the 5th and 6th waves from unilaterally hearing adults had significantly longer latencies. There were no differences between males and females.     

Complex segregation analysis of deafness in Dalmatians

OBJECTIVE: To use pedigree analysis to evaluate the feasibility of a major locus model for deafness in Dalmatians. ANIMALS: 605 purebred Dalmatians from 42 families. PROCEDURE: Hearing loss was evaluated through the brainstem auditory-evoked response. Dogs were classified into mutually exclusive categories: normal hearing, unilaterally deaf, or bilaterally deaf. Information was collected on sex, coat color, presence or absence of a color patch at birth, and eye color. Statistical analyses were performed by use of regressive logistic models designed for complex segregation analysis. Genetic correlations among eye color, deafness, and color patch were estimated. RESULTS: Prevalence of hearing loss was 11% for dogs classified as unilaterally deaf and 5% for dogs that were bilaterally deaf. Complex segregation analysis detected statistical evidence of a single allele with an expected frequency of 0.21 that had an effect on the prevalence of deafness. Results of analyses suggested that this locus cannot completely explain the inheritance and incidence of deafness in Dalmatians. Genetic correlation estimates among deafness, eye color, and color patch revealed strong interrelationships among these characteristics. CONCLUSIONS AND CLINICAL RELEVANCE: To reduce the incidence of hearing loss in Dalmatians, unilaterally deaf, blue-eyed dogs should not be considered as potential parents.     

Genetic predisposition to purine uroliths in Dalmatian dogs

Homozygosity for a defective recessive gene results in all Dalmatians having elevated concentrations of urine uric acid and predisposes them to formation of purine uroliths. Why some animals form uroliths and others do not is not known. In a pilot breeding experiment, the incidence of sensorineural deafness among backcrossed, high urine uric acid Dalmatians was significantly higher (probability less than 0.05) than among low urine uric acid siblings. Urine uric acid values for Dalmatians reported in the literature are not likely to be comparable, because uric acid appears to be more likely to precipitate in Dalmatian urine than in the urine of other dogs and man. Heating, alkalinization, and thorough mixing are required whenever specimens are transferred from one container to another or an aliquot is removed for assay.     

Does a pleiotropic gene explain deafness and blue irises in white cats?

The prevalence of deafness is high in cat populations in which the dominant white gene is segregating. The objective of this study was to investigate whether there is a gene that is responsible for deafness as well as for blue eyes and to establish a plausible mode of inheritance. For this purpose, data from an experimental colony with deaf cats were analyzed. The hearing status was determined by acoustically evoked brain stem responses (BAER). Complex segregation analyses were conducted to find out the most probable mode of inheritance using maximum likelihood procedures. The prevalence of deafness and partial hearing in the experimental colony was 67% and 29%, respectively. The results of the bivariate segregation analysis support the hypothesis of a pleiotropic major gene segregating for deafness and blue iris colour. The high heritability coefficients for both traits, 0.55 and 0.75 respectively, indicate that beside the major gene there is an important influence of polygenic effects.     

Histopathologic evidence of capecitabine corneal toxicity in dogs

In an experimental model of transplant rejection, renal transplants were performed on 6 mixed-breed dogs. Capecitabine (CPC) was administered as an oral immunosuppressive agent. All recipients received systemic CPC, cyclosporine (CSA), prednisolone, and famotidine throughout the study. Two dogs developed superficial keratitis, which was characterized by multifocal geographic erosions, superficial corneal epithelial pigmentation, and corneal neovascularization. These clinical signs correlated with the dose of CPC given, whereas other drug doses remained unchanged. After euthanasia, routine histologic sections were stained with hematoxylin and eosin and with alcian blue periodic acid-Schiff for light microscopic evaluation. Ocular histopathologic abnormalities were limited to neovascularization and inflammatory infiltrate of the anterior corneal stroma and abnormal basal cell morphology, disorganization, thinning, and pigmentation of the corneal epithelium. The purpose of this communication is to describe the clinical and histopathologic evidence of CPC corneal toxicity in dogs.     

Eye diseases in Siberian husky dogs

A full ophthalmic examination was performed on 40 Siberian husky dogs using direct and indirect ophthalmoscopy, gonloscopy and nasolacrimal cannulation. Eight (20%) of the dogs were found to have distichia, 10 (25%) had excessive medial caruncular hairs, 8 (20%) had absence, displacement, or narrowing of the nasolacrimal puncta, 2 (5%) had bilateral corneal crystalline opacities, and 2 (5%) had unilateral areas of lateral corneal lipidosis. Fifty percent of the dogs had some abnormality of the iridocorneal (drainage) angle. However, in only one of these was the deformity severe enough to require glaucoma prophylaxis. An association between blue iris colour and malformation of the iridocorneal angle was noted.     

Canine Dal blood type: A red cell antigen lacking in some Dalmatians

BACKGROUND: Based upon alloantibodies produced after sensitizing dogs with transfused blood, more than a dozen blood group systems have been recognized thus far, and some have been classified as dog erythrocyte antigens (DEA). HYPOTHESIS: A new canine red cell antigen was suspected, based on the development of specific alloantibodies in a Dalmatian previously sensitized by blood transfusions. ANIMALS: Twenty-six Dalmatians (including 1 Dalmatian in need of blood compatibility studies); 55 canine blood donors. METHODS: Serologic tests, including blood typing, crossmatching, and direct Coombs' test were performed by standard tube techniques and a novel gel column technology adapted from human blood banking. RESULTS: By day 40 after transfusion of an anemic Dalmatian, all major crossmatch tests to 55 non-Dalmatian dogs were incompatible. The 2 initial donors, who were compatible before transfusion, were also now incompatible, suggesting the development of an alloantibody to a common red cell antigen. No siblings were available, but 4 of 25 unrelated Dalmatians were crossmatch compatible, suggesting that they were missing the same red cell antigen. The patient was blood typed DEA 1.1, 3, 4, and 5 positive, but DEA 7 negative. Further blood typing and crossmatching results did not support an association to any of these known blood types. The alloantibodies produced were determined to be of the immunoglobulin G class. CONCLUSIONS AND CLINICAL IMPORTANCE: Based upon the identification of an acquired alloantibody in a Dalmatian, a presumably new common blood type named Dal was identified. Dalmatians lacking the Dal antigen are likely at risk of delayed and acute hemolytic transfusion reactions.     

Tracing the origin of 'blue Weimaraner' dogs by molecular genetics

Weimaraner dogs are defined by light brown coat colour termed grey including several shadings ranging from silver and deer to mouse grey. In contrast, the so-called blue Weimaraners (BW) with lightened black-pigmented coat have been proposed to represent spontaneous revertants in the Weimaraner breed. In order to investigate the genetic determinants of the characteristic grey coat colour versus those of BW, known variation in coat colour genes including TYRP1 and MLPH were analysed in a number of grey and blue dogs. Variations at the B locus cause grey coat colour in Weimaraners via two non-functional TYRP1 copies (bb) including the b(s), b(d) and b(c) alleles. In all BW, at least one functional TYRP1 allele (Bb or BB genotype) was identified. Defined microsatellite alleles in TYRP1 intron 4 are linked to this functional B allele in BW. These alleles were also detected in various other dog breeds, but not in grey Weimaraners. The combination of a dominant trait for blue versus grey together with a specific TYRP1 haplotype in BW suggests that blue coat colour is not the result of spontaneous (back-) mutation in grey Weimaraners. This inference is even emphasized by the presence of a unique Y-chomosomal haplotype in a male offspring of the supposed ancestor of the BW population which - according to pedigree information - carries a copy of the original Y chromosome. Thus, molecular genetic analyses of coat colours combined with Y-chromosomal haplotypes allow tracing the origin of atypical dogs in respective canine populations.     

The use of contralateral masking noise in the detection of unilateral deafness in Dalmatian puppies

BACKGROUND: The brainstem auditory-evoked response (BAER) is currently the standard evaluation method of hearing in dogs. In asymmetrical hearing loss in human patients, simultaneous presentation of masking noise to the nontest ear is routinely performed during BAER to eliminate the crossover effect. HYPOTHESIS: The crossover effect occurs during canine BAER, and masking noise of 20 decibels (dB) below click stimulus intensity is sufficient to abolish this effect. ANIMALS: Fifty-six Dalmatian puppies with confirmed unilateral deafness. METHODS: The BAER was elicited with 80 and 100 dB normalized hearing level (dBnHL) stimulus intensity in the deaf ear. The 100 dBnHL stimulus was repeated while simultaneously applying 80 dBnHL white masking noise to the nontest ear. RESULTS: Ten dogs were excluded because of BAER trace baseline fluctuation. In the remaining 46 dogs, 8 dogs had no waveforms, but 38 dogs had an identifiable wave-V in the deaf ear BAER at 80 dBnHL intensity stimulus. At 100 dBnHL intensity stimulus, all but 1 dog had a discernible wave-V in the deaf ear BAER. The deaf ear BAER waveforms were abolished by white masking noise at 80 dBnHL in the nontest ear in all dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Abolition of BAER wave-V in the deaf ear by white masking noise in the nontest ear suggests that this wave is caused by the crossover effect. beta distribution indicates 95% confidence that white masking noise, at 20 dB below click stimulus intensity, would abolish this crossover effect in over 90% of the dogs. This supports using masking noise in the nontest ear during canine BAER.     

Brainstem auditory evoked potential wave V latency-intensity function in normal Dalmatian and Beagle puppies

This study investigated whether Dalmatian puppies with normal hearing bilaterally had the same click-evoked brainstem auditory potential characteristics as age-matched dogs of another breed. Short-latency brainstem auditory potentials evoked by condensation and rarefaction clicks were recorded in 23 1.5- to 2-month-old Dalmatian puppies with normal hearing bilaterally by a qualitative brainstem auditory evoked potential test and in 16 Beagle dogs of the same age. For each stimulus intensity, from 90 dB normal hearing level down to the wave V threshold, the sum of the potentials evoked by the 2 kinds of stimuli were added, giving an equivalent to the alternate click polarity stimulation. The slope of the L segment of the wave V latency-intensity curve was steeper in Dalmatian (-40 +/- 10 micros/dB) than in Beagles (-28 +/- 5 micros/dB, P < .001) puppies. The hearing threshold was lower in the Beagle puppies (P < .05). These results suggest that interbreed differences may exist at the level of cochlear function in this age class. The wave V latency and wave V-wave I latencies differences at high stimulus intensity were different between the groups of puppies (4.3 +/- 0.2 and 2.5 +/- 0.2 milliseconds, respectively, for Beagles; and 4.1 +/- 0.2 and 2.3 +/- 0.2 milliseconds for Dalmatians, P < .05). A different maturation speed of the neural pathways is one possible explanation of this observation.