Molecular medicine
分子医学

Peekaboo
若隐若现（译/陈继龙）

Jun 7th 2007
From The Economist print edition

The search for genes that cause disease bags some new trophies
致病基因研究取得新突破

（1）ALTHOUGH cancer has become the proving ground of molecular medicine—the idea that proteins characteristic of a disease are the ones to aim at when designing therapies—the hope is that the approach will be more widely applicable than that. The first step towards realising this hope, of course, is to work out the nature of the molecules in question—and that is the purpose of a paper published this week in Nature by the members of the Wellcome Trust Case Control Consortium.
虽然癌症已成为验证分子医学的基础——分子医学认为，某一疾病的特征性蛋白可作为靶蛋白用于治疗研究，但人们仍希望能找到适用范围更广的疗法。要实现这一愿望，无疑首先要弄清有关分子的特性，而Wellcome Trust病例控制协会（Case Control Consortium）会员在本周《自然》杂志上发表的一篇论文，其目的也在于此。

One of the goals of the Human Genome Project was to allow researchers to link versions of individual genes (known as alleles) with particular diseases. （2）This has proved a lot harder than expected, because if lots of genes contribute to a disease, the signal from each is inevitably weakened. That means only large projects have much chance of working out what is going on. Hence the decision of Britain's biggest medical-research charity to put together the consortium that has just reported.
人类基因组计划（Human Genome Project）的目标之一就是要让研究者找出单个基因多个变体（亦即等位基因）与特定疾病之间的关联。事实证明，要达到这一目标非常困难，因为假如一种疾病与多个基因有关，每个基因所发出的信号就不可避免地减弱，这表明只有通过大规模的试验研究才有可能彻底弄清每个基因的具体作用。为此，作为英国最大的医学研究慈善机构，Wellcome Trust决定建立这样一个联合研究协会。

The researchers, all 256 of them, looked at seven diseases: bipolar disorder, coronary-artery disease, Crohn's disease (an inflammation of the gut), hypertension, rheumatoid arthritis, type I diabetes (the sort that develops early in life) and type II diabetes (the sort that develops later). They studied 2,000 people with each condition and compared them with 3,000 symptom-free individuals.（3） In each case they used devices called gene chips to look for associations between a disease and one or more of 500,000 so-called single-nucleotide polymorphisms (SNPs). These are places where the DNA of some individuals differs from that of others by a single molecular letter of the genetic code. Some SNPs occur in genes themselves. Others are found in the DNA between genes. But all act as markers that may be associated with different alleles of the same gene.
该协会的256名研究人员对7种疾病进行了研究，它们是躁狂抑郁症、冠心病、克罗恩病（一种肠炎）、高血压、类风湿性关节炎、I型糖尿病（早年发生的一种糖尿病）和II型糖尿病（晚年发生）。每种疾病选取了2000名患者作为研究对象，并与3000名健康人进行比照。研究采用了“基因芯片”，以检测某种疾病与单核苷酸多态性（single-nucleotide polymorphism，SNP）数量之间的相关性。SNP是指个体间的DNA差异由遗传密码中单个核苷酸所决定，而基因芯片可以检测到多达50万个SNP。虽然有的SNP出现在基因本身，而有的则出现在基因之间的DNA片段，但所有SNP均可作为标志物，呈现与同一基因的不同等位基因之间的相关性。

（4）The result was the discovery of 24 places in the genome so strongly associated with a disease that there was only one chance in 2m of the link being accidental. A further 58 associations had less than one chance in 100,000 of being wrong. The richest targets were Crohn's disease and type I diabetes, with nine and seven near-certainties respectively.
研究发现，一种疾病与基因组中24个SNP密切相关，且偶然关联的可能性只有二百万分之一。另外还有58个关联的SNP，其错误关联的可能性也不到十万分之一。拥有治疗靶基因最多的是克罗恩氏病和I型糖尿病，大致分别为9个和7个。

Some of the candidates corresponded to known genes. Others did not, and the next phase of the project will be to search the areas of the genome that the SNPs point at for likely genetic suspects. （5）Once these are discovered, the proteins they encode can be added to the lists of those that are targets for the molecular medicinal drug-makers.
有一些“候选基因”与已知基因是一致的，有些则不然，因此该研究计划下一步对基因组中SNP靶向区域进行研究，以求找出其中所可能具有的遗传特性。如获成功，这些基因所编码的蛋白就可与已有的靶蛋白一起受到分子药物生产商的青睐了。（陈继龙 草译）