Analysis of the mode of inheritance for distichiasis in the Elo dog breed using complex segregation analyses

The inheritance of distichiasis was analyzed in the dog breed Elo using complex segregation analyses.The different hypotheses of monogenic, mixed-monogenic-polygenic and polygenic inheritance as well as a pure environmental model were tested. In further analyses the number of examined Elo dogs per ophthalmologist and the proportion of genes of Eurasian and Old English Sheepdogs were included in the models as covariates. Seven families were randomly collected for the analyses.The seven families comprised a total of 296 animals with 218 examined and 65 affected dogs. A genetic component was verified for the prevalence of distichiasis. Mixed models with a recessive, dominant or arbitrary major gene effect and the polygenic model represented likely hypotheses of inheritance. The prevalence of distichiasis observed was insufficiently explained by non-genetic factors and the breed composition. Therefore, a model only including non-genetic factors and the breed composition could be excluded.     

FC-9 Coat funk in Alaskan malamutes

The purpose of this study was to describe a new hereditary sensory neuropathy in French spaniels resulting in analgesia and progressive mutilation of the distal extremities. Thirteen French spaniels (six females, seven males) from five different litters with acral mutilation were identified. Clinical signs were first noted between 3.5 and 12 months of age and typically consisted of sudden excessive and intense licking and biting of toes and/or footpads of one or several feet. This generally progressed rapidly into swollen digits, paronychia, footpad ulceration, and occasionally fracture and osteomyelitis. If the affected dogs were unrestrained, auto-amputation of claws, toes and footpads usually resulted. However, even in the more severe cases, affected dogs walked and ran on their mutilated feet without any evidence of lameness, pain or ataxia, and they allowed wound care without evidence of pain or discomfort. Dogs were otherwise healthy, with the exception of frequent secondary bacterial infections of the wounded feet. This disorder was clinically very difficult to manage, and the majority of the dogs were euthanized within days to months of diagnosis. None of the sires or dams of the affected dogs reported here were clinically affected. There was no apparent sex predilection. An autosomal recessive mode of inheritance was strongly suspected. The clinicopathological findings, the early age of onset and the disease progression in affected French spaniels were very similar to those reported for hereditary sensory neuropathy in German short-haired pointers, English pointers and English springer spaniels.
Funding: Self-funded.     

FC‐7 Acral mutilation and analgesia due to hereditary sensory neuropathy in 13 French spaniels

The purpose of this study was to describe a new hereditary sensory neuropathy in French spaniels resulting in analgesia and progressive mutilation of the distal extremities. Thirteen French spaniels (six females, seven males) from five different litters with acral mutilation were identified. Clinical signs were first noted between 3.5 and 12 months of age and typically consisted of sudden excessive and intense licking and biting of toes and/or footpads of one or several feet. This generally progressed rapidly into swollen digits, paronychia, footpad ulceration, and occasionally fracture and osteomyelitis. If the affected dogs were unrestrained, auto‐amputation of claws, toes and footpads usually resulted. However, even in the more severe cases, affected dogs walked and ran on their mutilated feet without any evidence of lameness, pain or ataxia, and they allowed wound care without evidence of pain or discomfort. Dogs were otherwise healthy, with the exception of frequent secondary bacterial infections of the wounded feet. This disorder was clinically very difficult to manage, and the majority of the dogs were euthanized within days to months of diagnosis. None of the sires or dams of the affected dogs reported here were clinically affected. There was no apparent sex predilection. An autosomal recessive mode of inheritance was strongly suspected. The clinicopathological findings, the early age of onset and the disease progression in affected French spaniels were very similar to those reported for hereditary sensory neuropathy in German short‐haired pointers, English pointers and English springer spaniels. Funding: Self‐funded.     

Evidence of Inheritance of Intrahepatic Portosystemic Shunts in Irish Wolfhounds

Background: The etiogenesis of congenital portosystemic shunt in dogs is not understood. In Irish Wolfhounds, intrahepatic portosystemic shunt (IHPSS) is thought to be hereditary, but the mode of inheritance is unknown.
Objectives: To document the genetic background and investigate the potential mode of inheritance of IHPSS in Irish Wolfhounds.
Animals: Three mature, privately owned, affected siblings and their progeny produced in 2 litters.
Methods: Prospective, observational study. Two test matings of 1 affected sire with 2 of his affected sisters were used to determine the inheritance pattern. Affection status was determined by measuring venous blood ammonia concentrations, detection of the shunt by ultrasonography and confirmation during surgical attenuation of the intrahepatic shunting vessel.
Results: In 1 litter of 5 pups all had an IHPSS. In the other litter 5 of 11 pups were affected. Both left- and right-sided shunts occurred in both litters. No sex predisposition was evident among affected dogs.
Conclusions and Clinical Importance: Our results show that IHPSS in Irish Wolfhounds is a familial disorder that is likely genetic. It is unlikely that the mode of inheritance is monogenic. A digenic, triallelic trait could explain the observed occurrence of IHPSS but other modes of inheritance cannot be excluded.     

Inherited congenital extrahepatic portosystemic shunts in Cairn terriers

The pathogenesis of congenital portosystemic shunt (CPSS) in dogs still is incompletely understood. In Irish Wolfhounds and Yorkshire Terriers, CPSS is reported to be hereditary. The aim of this study was to investigate a possible genetic basis and the mode of inheritance of CPSS in Cairn Terriers. Between July 1990 and July 2001, 6-week-old pups of the Dutch Cairn Terrier population were screened by measuring venous ammonia concentrations and in the presence of hyperammonemia by ultrasonography, autopsy, portal vein angiography, or exploratory celiotomy. The same successfully operated female was used 3 times in test matings with an unrelated affected male, her unaffected sire, and an affected offspring. The prevalence of CPSS in the general Cairn Terrier population, the direct progeny of frequently used males, and the offspring of the test matings were tested for significant differences. In total, 6,367 Cairn Terriers were screened; 32 males and 26 females had CPSS. In 3 large family groups, significantly higher prevalences were found compared with the general population (P < .0001, P < .0001, and P < .044). The prevalence of CPSS in the offspring of the test matings was significantly higher (P < .002) than in the general population. No sex predisposition occurred among the affected dogs. The higher prevalence of CPSS in the test matings and the 3 family groups compared with the general population indicates that CPSS in Cairn Terriers is a genetic disease. The inheritance is autosomal and most likely polygenic or monogenic with variable expression.     

Inheritance of equine sarcoid disease in Franches-Montagnes horses

The mode of inheritance for susceptibility to equine sarcoid disease (ES) remains unknown. The objectives of this study were to analyse a large sample of the Franches-Montagnes (FM) horse population and investigate the heritability and mode of inheritance for susceptibility to ES. Horses were clinically examined for the presence of sarcoid tumours. A standardized examination protocol and client questionnaire were used and a pedigree- and subsequent segregation-analysis for the ES trait performed. To investigate the mode of inheritance, five models were evaluated and compared in a hierarchical way.The analyses reveal that variation in susceptibility to ES is best explained by a model incorporating polygenic variation. The possible effect of a major gene, such as specific equine leukocyte antigen alleles, is unlikely, but cannot be ruled-out entirely. The heritability of the phenotype on the observation scale for the trait ‘affected with ES’ was estimated to be 8%. A corrected value for the heritability on a liability scale was estimated at 21% and it is therefore possible to estimate breeding values for ES. The arguments against the practical implementation of an estimated breeding value in a multifactorial condition like ES are discussed.     

Inherited alopecia X in Pomeranians

Four male Pomeranians that showed alopecia with an age of onset between five months and eight years were investigated.The aim of the investigation was to clarify whether the affected dogs had alopecia X and whether their symptoms might be due to a hereditary defect.The four affected dogs showed hairless patches at the root of the tail, at the back, at the limbs from the thigh to the tarsus and at the abdomen. Within the hairless patches some islets with sparse hair were present. In hairless patches the skin was dark pigmented. Besides the alopecia and hyperpigmentation no other symptoms were found according to anamnestic and clinical examination. History, clinical examinations, laboratory diagnostics, and histopathology of skin biopsies allowed the diagnosis of alopecia X in three affected male dogs.The last one of the affected dogs additionally had slightly reduced thyroid hormone levels. Based on identical symptoms and the close relatedness of all four animals, it was assumed that the fourth affected dog also had alopecia X.The available data possibly indicate a monogenic autosomal dominant inheritance, however a recessive inheritance can not be excluded at this time.     

Heritability of multifocal retinal dysplasia in American Cocker Spaniels

Multifocal retinal dysplasia was detected in 96 American Cocker Spaniels. Affected dogs were part of approximately 500 American Cocker Spaniels examined from 1972 to 1976 in statewide survey clinics for inherited cataracts and progressive retinal atrophy. The dysplastic retina was observable ophthalmoscopically in dogs as young as 3 to 4 weeks and as old as 7 years. Ophthalmoscopic features varied, depending on whether the dysplastic foci were in the tapetal or non-tapetal portion of the fundus. Over the tapetum, dysplastic foci appeared as multiple small irregularities of diminished and altered tapetal reflectivity. In the non-tapetal fundus, dysplasia appeared as areas of decreased pigmentation. Blindness or other apparent visual deficits were not observed in affected dogs. Histologic examination of affected eyes revealed focal dysplasia limited to the retina and optic nerve. Abnormalities included localized areas of retinal folding, rosettes, and retinal pigment epithelium hypertrophy and hyperplasia. Pedigree analysis demonstrated that 71 of the 96 affected dogs were related and could be identified in an extended pedigree. A recessive mode of inheritance was suggested, because in 5 litters (born to 10 affected parents), all 23 progeny that lived were affected. A dominant or polygenic mode of inheritance could not be ruled out.     

Risk ratio as parameter for the genetic characterization of complex binary traits in cattle. A simulation study under various genetic models using halfsib families

The risk ratio (λ_R) is defined as ‘the recurrence risk for a relative of an affected individual divided by the prevalence in the general population’ and is considered as the most important parameter when designing mapping experiments for diseases in humans. In this paper, the risk ratio was introduced as a parameter to genetically characterize complex binary traits such as mastitis in cattle. Simulations were applied to evaluate the properties of λ_R under different genetic models (monogenic, digenic, polygenic and mixed models) and in dependency of their parameters for a design consisting of unbalanced halfsib families typically found in dairy cattle. Population prevalences of the simulated data ranged from 5 to 40% and λ_R was estimated on a phenotypic level. In the discrete loci models complexity of the traits was introduced through different levels of penetrance and the proportions of phenocopies within each genetic background. The risk ratio and the power to reject the null hypothesis of independent halfsibs (λ_R=1) were influenced by the prevalence in all genetic models chosen. Absolute values for λ_R were higher for lower prevalences, for example, λ_R=2.77 and 1.62 for a pure monogenic recessive model with 5 and 20% prevalence, respectively, whereas the power decreases in the case of lower prevalences. For all the prevalences investigated, higher risk ratios were found for discrete loci models compared with the polygenic models, with higher values for the monogenic relative to the digenic models in general. For the mixed models, λ_R was intermediate between the polygenic and discrete loci models. Genes with dominant relative to recessive inheritance for susceptibility caused higher risk ratios in monogenic and mixed models, for example, λ_R=5.16 and 2.77 for a pure monogenic model with 5% prevalence. In the discrete loci models, λ_R decreased with lower penetrance and a higher proportion of phenocopies. Risk ratios increased with the heritability in the polygenic and in addition with the effect of the major gene in mixed models. Consistent patterns of risk ratios were observed under the analysed genetic models and parameters, which indicate that the risk ratio is a parameter well suited to genetically characterize binary traits in unbalanced halfsib families.     

Genetic aspects of Labrador Retriever myopathy

Labrador Retriever myopathy (LRM) has become a relatively common muscular disease. The objective of our prospective study was to determine by segregation analyses a plausible mode of inheritance within a Labrador Retriever population. Therefore we performed neurological examinations, as well as electromyographic and histopathological evaluations of 58 closely related dogs. Seven dogs with an average age of 27.8 months had clinical signs consistent with LRM including exercise intolerance or fatigue. The diagnosis was based on neurological deficits and confirmed by histopathological results of muscle biopsy. We found in all cases obvious differences in fiber calibre size associated with texture disturbances. In addition, we found 41 clinically normal dogs with histological findings consistent with LRM. Three genetic models, the major gene, the mixed inheritance as well as the environmental model, were evaluated by segregation analyses. They were applied to an extended pedigree including 164 non-randomly ascertained related Labradors. According to phenotype the clinically examined dogs were divided into two different data sets. One data set distinguished between clinically normal and abnormal dogs, the second data set between histopathologically normal and abnormal dogs. We concluded that the clinical form of LRM is transmitted by a major gene and controlled by an autosomal recessive mode of inheritance. Furthermore, for expression of the subclinical form an additional gene or an environmental factor is responsible. Our findings suggest that LRM is similar to limb-girdle muscular dystrophy in man and therefore, may be used in the future as an animal model.     

Clinical and Electrophysiological Characterization of Myokymia and Neuromyotonia in Jack Russell Terriers

Background: Generalized myokymia and neuromyotonia (M/NM) in Jack Russell Terriers (JRTs) is related to peripheral nerve hyperexcitability syndrome in humans, a symptom complex resulting from diverse etiologies. Objective: Clinical and electrodiagnostic evaluation is used to narrow the list of possible etiological diagnoses in JRTs with M/NM. Animals: Nine healthy JRTs and 8 affected JRTs. Methods: A prospective study was conducted comparing clinical and electrophysiological characteristics in 8 JRTs affected by M/NM with 9 healthy JRT controls. Results: All affected dogs except 1 had clinical signs typical of hereditary ataxia (HA). In 6 dogs, neuromyotonic discharges were recorded during electromyogram. Motor nerve conduction studies showed an axonal neuropathy in only 1 affected dog. Compared with controls, brainstem auditory‐evoked potentials (BAEP) showed prolonged latencies (P < .05) accompanied by the disappearance of wave components in 3 dogs. Onset latencies of tibial sensory‐evoked potentials (SEP) recorded at the lumbar intervertebral level were delayed in the affected group (P < .001). The BAEP and SEP results of the only neuromyotonic dog without ataxia were normal. Conclusions and Clinical Importance: The BAEP and spinal SEP abnormalities observed in JRTs with M/NM were associated with the presence of HA. Therefore, these electrophysiological findings presumably arise from the neurodegenerative changes characterizing HA and do not directly elucidate the pathogenesis of M/NM. An underlying neuronal ion channel dysfunction is thought to be the cause of M/NM in JRTs.     

Heritability estimations for diseases, coat color, body weight, and height in a birth cohort of Boxers

OBJECTIVE: To obtain heritability estimates for diseases and characteristics in Boxers. ANIMALS: Birth cohort of 2,929 purebred Boxers from 414 litters. PROCEDURE: Heritability estimates were determined for cheiloschisis-palatoschisis, cryptorchidism, epilepsy, stifle disorders, cardiac disorders, coat color, birth weight, and adult weight, and height. Binary traits were analyzed by use of a mixed-effects probit model. Some traits also were analyzed by use of a model that postulated monogenic inheritance. Full pedigree analyses were performed. Variation in incidences of disease among clusters of related dogs was evaluated. RESULTS: Heritability estimates were virtually zero for cardiac disorders, medium (0.17 to 0.36) for most other traits, and high (> 0.55) for coat color, birth weight, and adult height. Litter effects and risk factors affected cheiloschisis-palatoschisis, heart murmur, coat color, broadly defined epilepsy, and adult weight. Litter effects may be attributable to common environmental effects for littermates but also may be attributable to dominance variation caused by a recessive gene. Heritability estimates increased when stricter definitions for epilepsy and stifle disorders were used. The monogenic model did not reveal higher heritability estimates for 6 traits analyzed. Incidences for white coat differed significantly for 10 familial clusters, confirming high heritability and effects of familial lineage. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that genetic improvement of most traits should be feasible, except for cardiac disorders. However, because most traits are influenced by environmental effects as well as genetic effects, genetic counseling based on polygenic inheritance and use of familial information rather than strict exclusion of parents is preferred.     

Hereditary nephritis in the bull terrier: evidence for inheritance by an autosomal dominant gene

A high prevalence of renal failure has been reported in bull terriers in Australia. The pattern of inheritance was analysed in a family of 33 bull terriers in which 10 dogs had renal disease manifested by proteinuria, ultrastructural abnormalities in the glomerular basement membrane, renal failure, or 'end stage' kidneys. The presence of at least one affected parent for each affected offspring, the approximately equal male/female ratio and the apparent absence of 'generation-skipping', strongly supported an autosomal dominant mode of inheritance, assuming a fully penetrant single major gene locus. Further evidence was not compatible with either an autosomal recessive or X-linked inheritance pattern. This contrasts with the X-linked inheritance shown in Alport's-type human hereditary nephritis and hereditary glomerulopathy in the samoyeds. Hereditary nephritis in the bull terrier should be a useful model for non-Alport's-type human hereditary nephritis, which is also reported to have an autosomal dominant inheritance pattern.     

Clinical and genetic investigations of idiopathic epilepsy in the Bernese mountain dog

A study was conducted to investigate the clinical aspects and to define the mode of inheritance of idiopathic epilepsy in the Bernese mountain dog. Pedigree analyses were carried out on an open, non-preselected population of 4005 dogs. Five different subpopulations with 50 epileptic dogs from 13 generations were included. Almost all epileptic patients showed generalised seizures of the grand-mal type with a well-defined prodromal and postictal phase. The majority (62 per cent) of the epileptic dogs had had their first seizures at between one and three years of age and it was found that the age at first seizure was significantly (P < 0.05) lower in dogs from affected parental animals than in dogs from healthy parental animals. A clear predisposition for males was also noted. Additionally, there was no correlation between inbreeding coefficient and age at first seizure or incidence rate of seizures. The increased occurrence of the disease in different subpopulations and different families of the same sires or dams showed that there was a genetic basis for the condition in the Bernese mountain dog. Furthermore, the results of the pedigree analyses and binomial test support the hypothesis that idiopathic epilepsy has a polygenic, recessive mode of inheritance in the breed. Additional objective test-mating programmes would however be necessary to define the exact mode of inheritance.     

Genetic aspects of idiopathic epilepsy in Labrador retrievers

A study was undertaken to define the mode of inheritance of idiopathic epilepsy in Labrador retrievers in Switzerland. Seven hundred and ninety-two pedigree certificates from a population of healthy and epileptic dogs from 11 generations were evaluated. Forty-four different families (giving a total of 55 epileptic dogs) were included. Most patients showed generalised grand mal seizures and the onset was within one to three years in 41 per cent. Males were no more affected than females and the gender ratio between epileptic and control animals was not significantly different (P>0·05). Additionally, there was no difference in average total inbreeding coefficient between both sexes, or with respect to age of onset of seizures. The increased manifestation of seizures in some subpopulations and the repeated occurrence in different families of the same sires suggested that there was a genetic basis for the condition in the breed. Results of pedigree analyses and from use of the binomial test support the hypothesis of a polygenic, recessive mode of inheritance. However, only an objective test-mating programme is likely to define the exact mode of inheritance.     

Unusual vascular ring anomaly associated with a persistent right aortic arch and an aberrant left subclavian artery in German pinschers

The objective of this study was to describe a specific form of persistent right aortic arch (PRAA) in three German pinscher dogs and to analyse the mode of inheritance in the breed. This type of PRAA is characterised by a left retro-oesophageal subclavian artery in combination with a ligamentum arteriosum originating at the aberrant left subclavian artery (PRAA-SA-LA). This rare combination of anomalies has only been reported in two isolated cases in other dog breeds and the occurrence of any form of PRAA was not previously known to occur in the German pinscher. In the present study, 18 cases of this congenital anomaly were ascertained and their high degree of relatedness and inbreeding could be shown through pedigree analysis. Three of the affected dogs underwent further clinical investigations, and post-mortem examination (two cases) and findings at surgery (one case) verified the diagnosis of PRAA-SA-LA. A monogenic autosomal recessive mode of inheritance was not likely.     

Cerebellar cortical degeneration in adult American Staffordshire Terriers

Adult-onset cerebellar cortical degeneration recently has been reported in American Staffordshire Terriers. We describe the clinical and histopathologic features of this disease and examine its mode of inheritance in 63 affected dogs. The age at which neurologic deficits 1st were recognized varied from 18 months to 9 years, with the majority of dogs presented to veterinarians between 4 and 6 years of age. Time from onset of clinical signs to euthanasia varied from 6 months to 6.5 years, with the majority of affected dogs surviving from 2 to 4 years. Initial neurologic findings included stumbling, truncal sway, and ataxia exacerbated by lifting the head up and negotiating stairs. Signs progressed to obvious ataxia characterized by dysmetria, nystagmus, coarse intention tremor, variable loss of menace reaction, marked truncal sway, and falling with transient opisthotonus. With continued progression, dogs became unable to walk without falling repeatedly. Cerebellar atrophy was visible on magnetic resonance images and on gross pathology. Histopathologic findings included marked loss of Purkinje neurons with thinning of the molecular and granular layers and increased cellularity of the cerebellar nuclei. The closest common ancestor of the dogs was born in the 1950s and inheritance was most consistent with an autosomal recessive mode of transmission with a prevalence estimated at 1 in 400 dogs. This inherited disease is comparable to the group of diseases known as spinocerebellar ataxias in humans. Many spinocerebellar ataxias in humans are caused by nucleotide repeats, and this genetic aberration merits investigation as a potential cause of the disease in American Staffordshire Terriers.     

Hereditary aspects of occipital bone hypoplasia and syringomyelia (Chiari type I malformation) in cavalier King Charles spaniels

A database of over 1300 cavalier King Charles spaniels spanning 20 generations was established by obtaining pedigree information from 45 dogs with syringomyelia secondary to occipital bone hypoplasia. These data were supplemented with published information from the breed club. The incidence of syringomyelia was very high in certain families and lines which had been extensively inbred. The affected dogs could be traced back to one bitch born in 1956 and the two offspring from her single litter. Four key dogs representing four major breeding lines consistently occurred within the individual pedigrees. If a dog had more than five of its eight great-grandparents descended from these four lines there was a greater chance of it having syringomyelia. The data from this preliminary study suggest that occipital bone hypoplasia is hereditary in the cavalier King Charles spaniel and that its inheritance is more likely to be autosomal recessive because both dam and sire must be inbred descendants from certain lines. However, the inheritance is more likely to be of variable penetrance or oligogenic than simple.