RESUMO
GATA4 is expressed early in the developing heart where it plays a key role in regulating the expression of genes encoding myocardial contractile proteins. Gene mutations in the human GATA4 have been implicated in various congenital heart defects (CHD), including atrial septal defect (ASD). Although ASD is the third most common CHD in humans, it is generally rare in dogs and cats. There is also no obvious predilection for ASD in dogs and cats, based on sex or breed. However, among dogs, the incidence rate of ASD is relatively high in Samoyeds and Doberman Pinschers, where its inheritance and genetic aetiology are not well understood. In this study, we identified and investigated the genetic aetiology of an ASD affected family in a pure breed dog population. Although the GATA4 gene was screened, we did not find any mutations that would result in the alteration of the coding sequence and hence, the predicted GATA4 structure and function. Although the aetiology of ASD is multifactorial, our findings indicate that GATA4 may not be responsible for the ASD in the dogs used in this study. However, this does not eliminate GATA4 as a candidate for ASD in other dog breeds.
Assuntos
Doenças do Cão/genética , Cães/genética , Fator de Transcrição GATA4/genética , Comunicação Interatrial/veterinária , Sequência de Aminoácidos , Animais , Sequência de Bases , Análise Mutacional de DNA , Primers do DNA/genética , Cães/classificação , Feminino , Comunicação Interatrial/genética , Masculino , Dados de Sequência Molecular , Linhagem , Homologia de Sequência de Aminoácidos , Especificidade da EspécieAssuntos
Cobre/metabolismo , Doenças do Cão/genética , Cães/genética , Erros Inatos do Metabolismo dos Metais/veterinária , Animais , Sequência de Bases , Primers do DNA/genética , Éxons , Feminino , Masculino , Erros Inatos do Metabolismo dos Metais/genética , Deleção de Sequência , Especificidade da EspécieAssuntos
Proteínas de Transporte de Ânions/genética , Displasia Pélvica Canina/genética , Sequência de Aminoácidos , Animais , Cães , Expressão Gênica , Testes Genéticos , Displasia Pélvica Canina/metabolismo , Masculino , Dados de Sequência Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Sulfatos/metabolismoRESUMO
Connexin 40 (Cx40) is a gap-junction protein expressed in the heart where it mediates the coordinated electrical activation of the atria and ventricular conduction tissues, facilitates cell-to-cell adhesion, and provides pathways for direct intercellular communication. Recent studies have shown that Cx40 null mice have cardiac conduction abnormalities with a very high incidence of cardiac malformations in heterozygous (18%) and homozygous (33%) animals, indicating that Cx40 plays a vital role in cardiomorphogenesis. Since several inherited cardiac conduction defects have also been found in dogs, we hypothesized that the clinical findings are genetically linked to a tissue-specific mutation or mutations in the canine Cx40 gene. We therefore screened the Cx40 gene in dogs with inherited cardiac conduction defects for mutations. In this study, we have identified three heterozygous base changes (C384G, C402T, C837T) in the dogs screened and determined them to be synonymous mutations. These mutations, however, have recently been found in an unrelated group of normal dogs.