Analysis of systematic effects on congenital sensorineural deafness in German Dalmatian dogs
Introduction
Congenital sensorineural deafness (CSD) has been known as a segregating defect in the Dalmatian dog breed for more than 100 years. In some studies higher prevalences of CSD were found in Dalmatian dogs with blue eyes. Degenerative changes of the inner ear usually occur before four to five weeks of age. Typically, Dalmatian dogs exhibit cochleo-saccular degeneration of type Scheibe (Igarashi et al., 1972; Mair, 1976). Neuronal degeneration that follows cochlear degeneration evolves slowly over years (Mair, 1976; Niparko and Finger, 1997).
Although CSD in Dalmatian dogs is known to be inherited, the number of contributing genes has not been identified, nor have their effects and interactions on phenotypic expression. The mode of inheritance has been discussed controversially in the literature. Using complex segregation analysis Famula et al. (2000) found involvement of a major gene in CSD of Dalmatian dogs in addition to polygenic components. Greibrokk (1994) interpreted his results in Norwegian Dalmatian dogs as due to transmission of an autosomal multifactorial recessive gene with incomplete penetrance. Other hypotheses on inheritance involve two different genes, requiring at least one dominant allele at each gene locus (Nelson, 1991), an X-linked gene with different expressivity (Anderson et al., 1968), two recessive genes of different origin (Strain et al., 1992), or polygenic determination (Famula et al., 1996). A Swiss study by Muhle et al. (2002) could not distinguish between the polygenic and monogenic inheritance models.
The association of CSD to the extreme white piebald allele sw in Dalmatian dogs seems to be generally accepted, but the genetic mechanisms for this relationship are unknown. Strain et al. (1992) suggested that the mutation for CSD in one American Dalmatian population encompassed gene loci, which determine both hearing function and pigmentation, while in the other population the mutation affected only hearing function. The alternative explanation was to assume an autosomal dominant pleiotropic gene with incomplete penetrance. However, this latter explanation for the different patterns of associations between CSD and phenotypic colour markers in three regions of the USA was not supported by the results of the study performed by Strain et al. (1992). Cattanach (1999) proposed that different expression levels of the sw allele modulate melanoblast numbers and migration as well as a different distribution of melanocytes in skin, eyes and the inner ear. It seems reasonable that genes affecting these developmental processes may play a role in the expression of CSD in Dalmatian dogs.
In man, hearing loss is the most frequent sensory defect. The number of genes accounting for hearing loss has been estimated at between 30 and 100 (Morton, 1991). Autosomal recessive forms account for about 85% of the cases, autosomal dominant forms for 15% and X-linked forms for 1–3%. Mitochondrial mutations with maternally transmitted hearing loss may also be possible (Petit, 1996). The difficulties in molecular genetic analysis of genes responsible for isolated deafness in man result from extreme genetic heterogeneity and the absence of criteria allowing the differentiation between the various inner ear defects caused by different genes. In order to circumvent these problems encountered in gene mapping, careful selection of study populations is necessary. The approaches consist of selecting populations or families in which the chance of segregation by more than one mutated gene is minimized. This is accomplished by selection of geographically isolated families or populations without immigration. High density genome screens are necessary for efficient analysis in small families. The power of detection could be improved if prior knowledge of a single segregating gene was available.
Detection of major genes segregating in deaf Dalmatian dogs, for example by the use of regressive logistic models (Bonney, 1986), would permit rapid progress in molecular genetic analysis and enhance our understanding of the development of inner ear defects. The implications for practical breeders would be that it would be possible to design breeding programmes for effective reduction of this congenital ear defect. However, prior to an analysis of the mode of inheritance, systematic effects must be evaluated.
The objectives of the present study were to analyse systematic effects on CSD in German Dalmatian dogs by employing animal model analyses. These analyses should clarify whether genetic variation is still present after correction for phenotypic colour markers such as eye colour, pigmentation of coat in puppies (patches) and other systematic effects. So these analyses would make it possible to draw conclusions on the size of genetic variation not associated with specific colour variants of Dalmatian dogs.
Section snippets
Materials and methods
Data were made available by the German Dalmatian kennel clubs associated with the VDH (Verein für das Deutsche Hundewesen, German Association for Dog Breeding and Husbandry, Dortmund, Germany). Kennel clubs supplying data were the DDC (German Dalmatian Club), CDF (Club for Friends of Dalmatian dogs), and DVD (Association for Dalmatian dogs in Germany). Deafness records based on brainstem auditory-evoked response (BAER) were collected from 1899 Dalmatians dogs being examined between 1986 and
Results
The significance of the fixed systematic effects is shown in Table 4. The sole significant effects were presence of blue eyes, percentage of puppies examined per litter and kennel club. The estimates of the fixed significant effects are given in Table 5. CSD was encoded as 0, 1, and 2 for normal hearing status, unilateral deafness, and bilateral deafness, respectively, and the estimates indicate the number of deaf ears (NDE). The prevalence of NDE was significantly higher in puppies with one or
Discussion
The objective of this study was to analyse the additive genetic variance of CSD in German Dalmatian dogs simultaneously with other important systematic effects and to evaluate the importance of phenotypic traits specific to Dalmatian dogs on the prevalence of CSD. The prevalence of CSD in our data was higher than in other studies of CSD for Dalmatian dogs in Europe (Greibrokk, 1994; Muhle et al., 2002; Wood and Lakhani, 1997), but lower than in American studies (Famula et al., 1996; Holliday et
References (19)
- et al.
Further contributions to the genetic aspect of congenital sensorineural deafness in Dalmatians
The Veterinary Journal
(2002) - et al.
Cochlear nucleus cell size changes in the dalmatian: model of congenital deafness
Otolaryngology—Head and Neck Surgery
(1997) - et al.
Prevalence and prevention of deafness in the Dalmatian assessing the effect of parental hearing status and gender using ordinary logistic and generalized random litter effect models
The Veterinary Journal
(1997) - et al.
Genetic hearing impairment in the dog
Acta Oto-Laryngologica Supplement
(1968) Regressive logistic models for familial disease and other binary traits
Biometrics
(1986)The ‘dalmatian dilemma’: white coat colour and deafness
Journal of Small Animal Practice
(1999)- et al.
A threshold model analysis of deafness in Dalmatians
Mammalian Genome
(1996) - et al.
Complex segregation analysis of deafness in Dalmatians
American Journal of Veterinary Research
(2000) Hereditary deafness in the Dalmatian: relationship to eye and coat color
Journal of the American Hospital Association
(1994)
Cited by (30)
The dog 2.0: Lessons learned from the past
2020, TheriogenologyCitation Excerpt :Special attention should be given to disorders directly or indirectly related to the breed standards. Examples are numerous and include the association between the dorsal hair ridge and dermoid sinus in the Rhodesian Ridgeback, brachycephalic obstructive airway syndrome in brachycephalic dogs and deafness and patching in the Dalmatian [19,50–53]. Whereas unwanted phenotypes not linked to the breed standard can be selected against within the context of ethical breeding, this is far more difficult when a phenotype is directly related to the actual breed standard.
Prevalence, heritability and genetic correlations of congenital sensorineural deafness and pigmentation phenotypes in the Border Collie
2011, Veterinary JournalCitation Excerpt :The heritability estimate of dichotomous deafness using a logistic model was the highest of all estimates (0.45), but similar in magnitude to that estimated for trichotomous deafness using a multivariate linear model (0.42). Previous studies on heritability of deafness as a trichotomous trait have reported estimates ranging from 0.27 (Juraschko et al., 2003b) to 0.76 (Famula et al., 2001), although direct comparison of heritability of deafness in different breeds is difficult due to variations in population size, sampling methods, breeding standards and prevalence of deafness within each population. The heritability estimate of the degree of white pigmentation on the head was far smaller than those for deafness or the number of blue eyes.
Handbook of Veterinary Neurology
2010, Handbook of Veterinary NeurologyAnimal breeding and genomics: Perspectives for dog breeding
2005, Veterinary JournalDeafness prevalence and pigmentation and gender associations in dog breeds at risk
2004, Veterinary Journal