Heritability and Segregation Analysis of Deafness in U.S. Dalmatians

Abstract

Hereditary loss of hearing affects many breeds of the domestic dog, but the Dalmatian has the highest prevalence. Approximately 30% are affected in the United States (U.S.) population. It is widely accepted that a relationship exists between deafness and pigmentation in the dog and also in other animals. While the Dalmatian exemplifies this relationship, the genetic origin and mode of inheritance of deafness in this breed are unknown. The goals of this study were to: (1) estimate the heritability of deafness in an extended kindred of U.S. Dalmatians and (2) determine, through complex segregation analysis, whether there is a major segregating locus that has a large effect on the expression of deafness. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N ϭ 148) had normal hearing, 18.1% (N ϭ 36) were unilaterally deaf, and 7.5% (N ϭ 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 considering it as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a single major gene affecting the disorder is not persuasive.

Prevalence of Unilateral and Bilateral Deafness in Border Collies and Association with Phenotype

“…25 Several studies have demonstrated that congenital deafness is inherited in Dalmatians, but the exact mechanism is controversial. 9,23 Neither a dominant nor a recessive simple Mendelian mode of transmission could be proven by pedigree analysis. 9,23 Other hypotheses on inheritance have included a model of 2 interacting recessive loci with incomplete penetrance 5 and polygenic determination.…”

“…[3][4][5][6][7][8] Dogs who are deaf by this age are considered to be affected with congenital sensorineural deafness. 1,4,6,7 Although most studies of congenital deafness have formerly been carried out on the Dalmatian, 5,[8][9][10][11][12][13][14][15][16][17] the prevalence of congenital deafness in the Bull Terrier, English Setter, Pointer, Catahoula Leopard dog, Whippet, Australian Cattle dog, Jack Russell Terrier, Dachshund, and English Cocker Spaniel has also been evaluated. 5,[17][18][19] In fact, more than 60 breeds of dog have now been identified as suffering from congenital sensorineural deafness, 17 including the Border Collie.…”

“…14,17 The lower prevalence of congenital deafness in Dalmatians in the UK, where blue-eyed dogs are not allowed for breeding, seems to support this. 5,[8][9][10]13 Blue eyes are accepted in the breed standard for Border Collies with a merle coat color.…”

Evidence of a Major Gene From Bayesian Segregation Analyses of Liability to Osteochondral Diseases in Pigs

“…Hence none of the results from our study could be compared with the literature, except for polygenic parameters for osteochondrosis (e.g., Kadarmideen et al 2004). In addition, only a few studies have investigated complex segregation analysis for ordinal or binary data (e.g., Thaller et al 1996;Cargill et al 2004) but this is the first study to extensively investigate a liability or threshold model method for identifying major genes for binary diseases in complex pedigrees with inbreeding and marriage loops. The basic theory and algorithms developed in this study could also be used in humans and companion animals (e.g., horses, cats, and dogs) where (poly-or oligogenic) diseases/disorders are observed in categorical form.…”

“…Inbreeding and marriage loops in a typical segregation analysis using pedigreed populations make the exact computations of likelihoods or marginal densities impossible. This problem has been overcome by the development of a Bayesian method implemented via Gibbs sampling, a Monte Carlo Markov chain (MCMC) methodology (Guo and Thompson 1992), and the application of this methodology to livestock populations ( Janss et al 1997;Hagger et al 2004;Ilahi and Kadarmideen 2004) as well as to companion animals (Cargill et al 2004). 1 No investigations have been carried out so far to determine the mode of inheritance of osteochondrosis in animals (in particular, pigs) by a complex segregation analysis.…”