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首页> 外文期刊>Journal of the Mass Spectrometry Society of Japan >分子病の質量分析：Δmによる分子診断
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分子病の質量分析：Δmによる分子診断

机译：分子疾病的质量分析：通过Δ m 进行分子诊断

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“Molecular disease” is defined as any disease in which the pathogenesis can be traced to a single molecule, usually a protein, which is either abnormal in structure or present in reduced amounts. In 1949, Linus Pauling coined this term in his report on the discovery of an electrophoretic change indicating the existence of a structural abnormality in hemoglobin derived from patients with sickle cell anemia. A change in the primary structure of proteins, typically amino acid substitutions (point mutations), and in post-translational modification as well causes a change in the molecular mass and thus should be detectable by mass spectrometry (MS). This was first proved in 1981 by the field desorption MS, which characterized 36Pro→Thr in a tryptic peptide of β globin from a polycythemic patient. A distinct merit of MS was its ability to detect “silent” mutations which are not amenable to conventional analytical methods including electrophoresis and chromatography. Another advantage was a high probability of the unique determination of the type and position of amino acid substitution within a specific peptide even in the case of the analysis of a complex mixture of peptides. This could be more reliably performed by multiple peptide maps from different proteolytic enzymes. In a subsequent achievement, in 1991, electrospray ionization was used to identify a lack of N-linked oligosaccharides in the serum transferrin from developmentally retarded patients. This discovery triggered the excavation of a new large disease group Congenital Disorders of Glycosylation (CDG), which are currently diagnosed at an incidence of approximately 1% in psychomotor retarded patients by MS in the author's laboratory. Mass measurement using the same strategy was also applied to the DNA molecules amplified by the polymerase chain reaction in the late 1990s. This article is a review of the studies on which the author received the MSSJ Award for Distinguished Contribution MS 2012.
机译：“分子疾病”定义为可将发病机理追溯到单个分子（通常是蛋白质）的任何疾病，该疾病结构异常或数量减少。 1949年，莱纳斯·鲍林（Linus Pauling）在他的报告中创造了这个术语，该发现是电泳变化的发现，表明来自镰状细胞性贫血患者的血红蛋白存在结构异常。蛋白质一级结构的变化（通常是氨基酸取代（点突变））以及翻译后修饰中的变化也会引起分子质量的变化，因此应通过质谱（MS）进行检测。这首先是在1981年由现场解吸质谱仪证明的，该质谱仪以多囊性患者的β珠蛋白的胰蛋白酶肽中的36Pro→Thr为特征。 MS的一个独特优点是它具有检测“沉默”突变的能力，这种能力不适用于常规分析方法，包括电泳和色谱分析。另一个优点是，即使在分析复杂的肽混合物的情况下，也可以独特地确定特定肽中氨基酸取代的类型和位置。这可以通过来自不同蛋白水解酶的多个肽图更可靠地进行。在随后的一项成就中，1991年，电喷雾电离被用于确定发育迟缓患者血清转铁蛋白中缺乏N-连接寡糖。这一发现触发了新的大型疾病组先天性糖基化疾病（CDG）的发掘，该疾病目前在作者的实验室中被MS诊断为精神运动障碍患者的约1％。使用相同策略的质量测量也应用于1990年代后期通过聚合酶链反应扩增的DNA分子。本文是作者获得MSSJ杰出贡献奖MS 2012的研究综述。

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