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Published on: May 16, 2020
A predictive model for canine dilated cardiomyopathy-a meta-analysis of Doberman Pinscher data
Siobhan Simpson1, Jennifer Edwards1, Richard D Emes2
1School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham , Leicestershire , UK.
Insights
Dilated cardiomyopathy, a heart condition affecting humans and dogs, may involve multiple genes. This study found a link between known genetic factors and an unknown X-linked gene, explaining sex differences in the disease.
Area of Science:
- Veterinary Cardiology
- Human Genetics
- Comparative Genomics
Background:
- Dilated cardiomyopathy (DCM) is a significant cardiac disease in humans and dogs, characterized by enlarged ventricles and impaired systolic function, often leading to heart failure.
- While human DCM has implicated genetic loci, these are mostly linked to rare monogenic forms, leaving the role of multigenic interactions poorly understood.
- Canine DCM shares functional similarities with human DCM, yet known human DCM loci are often excluded in dogs, suggesting distinct genetic factors.
Purpose of the Study:
- To investigate potential multigenic interactions in canine dilated cardiomyopathy.
- To explore the relationship between sex chromosome genotype (XX vs. XY) and known DCM loci on chromosome 5 and the PDK4 gene.
- To identify novel genetic factors contributing to DCM incidence and progression, particularly those influencing sex disparities.
Main Methods:
- A meta-analysis of existing canine dilated cardiomyopathy genetic datasets was performed.
- The study analyzed interactions between sex chromosome genotype, chromosome 5 loci, and the PDK4 gene.
- Statistical methods were employed to identify significant genetic associations and interactions.
Main Results:
- The analysis revealed a significant interaction between established canine dilated cardiomyopathy loci and an unidentified X-linked locus.
- This interaction suggests a multigenic contribution to the development and progression of dilated cardiomyopathy.
- The findings provide evidence for a genetic basis underlying the observed sex-disparity in DCM outcomes.
Conclusions:
- This study is the first to demonstrate a multigenic contribution to dilated cardiomyopathy.
- An interaction between known DCM loci and an X-linked locus is implicated in the disease.
- These genetic interactions may explain the sex-based differences in dilated cardiomyopathy incidence and severity.
Abstract:
Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY) with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes.
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