<International Circulation>: What is the value of genome scans for predicting sudden cardiac death?

  《国际循环》：基因检测对于预测心源性猝死的价值如何？
    Prof.Tomaselli: The value of genome scans for predicting sudden cardiac death is still experimental. Common variants in the human genome may make a small impact which cumulatively may have a large impact on phenotype. We are doing them in our own lab trying to figure out what things might be important. What common variants might be important and contribute to risk. And that is not just in genes that control susceptibility but genes that control thrombosis and a whole host of other things that we know impact on the heart. Right now， we are not in a position to use genome-wide associations or even selected genome scans for common variants to prognosticate. On the other hand， rare variants do have prognostic significance. For rare variants in the genome and those things that are associated with an inherited sudden death syndrome such as long QT syndrome， CPVT and Brugada syndrome for example， genotyping does seem to help although they still remain clinical diagnoses. It does help to inform as to who is at risk particularly not amongst people that present but amongst their family members as to who else is at risk of having an event. Genome-wide scanning is done and will be done differently in the near future. Array-based scanning is probably what is done most commonly now but high-dimensional sequencing and DNA sequencing is what will take over as machines can sequence tens of millions of base pairs of DNA and do it deeply. That will be the way to go and we will get more robust data there. It is still going to be a large bioinformatics problem and synthesizing the effect of what are not likely to be one or two or even three common variants but perhaps hundreds of common variants each of which make a small contribution but together make a big contribution and increase the risk in a significant way whereby you should act on it. There is nothing now on a genome-wide scan for anything that would cause me to actionably do something for a disease at this point.

    Tomaselli教授：基因检测对于预测心源性猝死的价值的价值目前还停留在实验性阶段。人类基因的常见变异会将较小影响累积，而对表型影响较大。我们在自己的实验室中进行研究来寻找重要因素，哪些常见变异重要，会增加风险。这些变异不光包括控制敏感性的基因，还有控制血栓的基因，以及其他对心脏产生影响的基因。目前，我们尚无法通过对应用基因组或甚至选定基因进行常见变异的检查来进行预测。另外一方面，一些罕见的变异的确有预测价值。基因的罕见变异与包括长QT综合征、多形性室速以及Brugada综合征在内的在内的遗传性猝死综合征相关，基因型检测可以帮助患者，尽管不能改变临床诊断。基因型检测可以告知患者以及他们的家庭成员，谁有发生心源性猝死的风险。基因组检测会在不久的将来进行。基于方阵的检查可能是目前最常见的检查，但是因为机器可以对上千万个DNA碱基对测序，因此高维测序和DNA测序会取代它。这是我们未来的方向，我们会取得更有力的数据。但是，对于变异的综合作用不是在一两个甚至三个常见变异上，而可能是几百个常见变异的总和，其中每一个变异作用都很小，但是加在一起就作用巨大，显著增加应当进行干预的风险，这仍然是一个很大的生物信息学问题。目前，还没有一种能让我对一个疾病采取行动的基因组检测