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A Systems Biology Approach to Decipher Genetic Variants in a Canine Model of Sudden Cardiac Death

机译:一种突然心脏死亡犬模型解码遗传变异的系统生物学方法

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Sudden cardiac death (SCD) represents a major public health challenge, accounting for approximately 25% of all cardiac deaths. It refers to an unexpected death from ventricular arrhythmia, occurring in individuals with preexisting cardiovascular disorders as well as in individuals not previously diagnosed with heart disease. The identification of genetic variants that increase susceptibility to SCD is fundamental to improve risk stratification and understanding of molecular pathophysiology. In this study, to investigate the molecular mechanisms underlying SCD, a canine model, recapitulating what may happen to patients with a prior myocardial infarction, was used to accomplish a genome-wide association study comparing dogs resulting susceptible or resistant to ventricular fibrillation during submaximal exercise. The identified variants were explored by means of a systems biology approach, which maps human ortho-logues of mutated genes into a network encompassing co-expression and physical interactions. The paths connecting mutated genes highlighted a subnetwork enriched for genes involved in regulation of cardiac function.
机译:突然的心脏死亡(SCD)代表了一个主要的公共卫生挑战,占所有心脏病的25%。它是指心室心律失常的意外死亡,在具有预先存在的心血管疾病的个体中发生,以及以前未被诊断出心脏病的个体。鉴定增加对SCD的易感性的遗传变异是提高风险分层和对分子病理生理学的理解的基础。在这项研究中,为了研究SCD的分子机制,犬模型,重新承诺在患有先前心肌梗死的患者对可能发生的患者可能发生的基因组关联研究比较犬在潜水运动期间对心室颤动的敏感或耐心室颤动进行比较。通过系统生物学方法探索所识别的变体,其将突变基因的人右侧映射到包含共同表达和物理相互作用的网络。连接突变基因的途径突出了富集的子网,富集参与心脏功能调节的基因。

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