Complex segregation analysis of dilated cardiomyopathy (DCM) in Irish wolfhounds

Abstract

The objective of the present study was to analyse the mode of inheritance for dilated cardiomyopathy (DCM) in Irish wolfhounds using regressive logistic models by testing for mechanisms of genetic transmission. Insights from this spontaneous animal model should aid importantly in understanding basic pathogenic mechanisms with regard to genetics and molecular biology of DCM in humans. Moreover, a procedure for the simultaneous prediction of breeding values and the estimation of genotype probabilities for DCM is expected to markedly improve breeding programmes. Results of cardiovascular examinations of 1018 dogs carried out between 1987 and 2003 by one veterinarian were analysed. Data of 878 dogs from 531 litters in 147 different kennels were used for complex segregation analyses. Pedigree information was available for more than 15 generations. Male dogs were affected significantly more often by DCM than female dogs. The segregation analysis showed that among all other tested models a mixed monogenic-polygenic model including a sex-dependent allele effect best explained the segregation of affected animals in the pedigrees. A pure monogenic inheritance of DCM could be significantly rejected in favour of the major gene and most general model. The gene action of the major gene was significantly different between female and male dogs.

Multiple Loci Are Associated with Dilated Cardiomyopathy in Irish Wolfhounds

“…This suggests a protective effect in female Irish wolfhounds. A major gene model with sex-specific allele effects was the most plausible explanation for the inheritance of DCM in Irish wolfhounds whereas a monogenic mode of inheritance of DCM had been rejected using complex segregation analysis [26]. Echocardiographic reference values have been established for Irish wolfhounds, facilitating the diagnosis of DCM in this breed [27], [28].…”

Dépistage de la cardiomyopathie dilatée et de la fibrillation atriale chez le Lévrier Irlandais

“…La recherche des gènes responsables est en cours mais n'a pas encore abouti. L'hypothèse initiale d'une transmission monogénique autosomale dominante n'a pu être vérifiée et la transmission suit un mode polygénique beaucoup plus complexe et encore imparfaitement connu (Distl et al 2007, Philipp et al 2012 …”

Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy

“…In human DCM there is often a heritable genetic basis of this disease [3, 4]. In several dog breeds, including IWH, canine DCM has been shown to have heritable component [5–7]. The heritability of canine DCM and its clinical resemblance to human DCM suggest that there is also a genetic basis to canine DCM [8, 9].…”

“…Possible reasons for the lack of identified genetic associations include the use of inappropriate control populations, incomplete clinical characterisation of control and affected populations, inadequate samples sizes, or an assumption of simple- Mendelian inheritance, despite the evidence suggesting more complex multifactorial influences on heritability [5]. Inappropriate controls have included unaffected individuals from different breeds to the affected individuals, or young individuals that still have the potential to develop disease [27–29].…”