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.
Dilated cardiomyopathy (DCM) is a common disease in humans and dogs. Large-breed dogs and especially Irish wolfhounds belong to the frequently affected breeds. Male Irish wolfhounds show a significantly higher prevalence of DCM than females. Therefore, we evaluated X chromosome markers for linkage with DCM as well as a human candidate gene on the X chromosome. A set of X chromosomal microsatellites was genotyped in Irish wolfhound families segregating for DCM. In addition, exon and intron sequences of the tafazzin (TAZ) gene were assayed for polymorphisms segregating in these families. Statistical analysis of the microsatellite markers did not reveal linkage to DCM. Furthermore, all Irish wolfhounds included in this study were monomorphic for TAZ, and only 8 sequence differences to the Dog Genome Assembly 2.1 could be found. The results indicate that due to the lack of mutations, TAZ is unlikely to cause DCM in Irish wolfhounds.
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