Nienhuis A W, Ley T, Pepe G, Tam J, Kantor J
Birth Defects Orig Artic Ser. 1982;18(7):69-79.
Our studies have shown that globin-gene structure, as revealed by Southern blot analysis, is normal in most patients who are homozygous for beta-thalassemia. In many, but not all patients, evidence for mutations which alter the metabolism of beta-globin RNA molecules was obtained by several methods of analysis. The most specific and sensitive of these involves the use of single-stranded, highly radioactive probes generated using the M13 cloning system. Such probes allow detection of aberrantly processed RNA molecules by S1 nuclease analysis, thereby providing clues as to the position and nature of mutations within individual thalassemic globin genes. Of greatest potential interest are those genes which provide no evidence, in bone marrow RNA, of aberrantly processed intermediates. Analysis of these genes by molecular cloning and DNA sequencing may lead to identification of sequences which are important for initiation or termination of RNA transcription. Mutations which cause beta-thalassemia continue to provide a rich source of information about the nature of DNA sequences which are essential for efficient gene expression. By study of thalassemic patients, new insights are obtained into normal mRNA metabolism.
我们的研究表明，通过Southern印迹分析揭示的珠蛋白基因结构，在大多数β地中海贫血纯合子患者中是正常的。在许多但并非所有患者中，通过几种分析方法获得了改变β珠蛋白RNA分子代谢的突变证据。其中最特异和敏感的方法涉及使用通过M13克隆系统产生的单链、高放射性探针。此类探针可通过S1核酸酶分析检测异常加工的RNA分子，从而为各个地中海贫血珠蛋白基因内突变的位置和性质提供线索。最具潜在意义的是那些在骨髓RNA中未提供异常加工中间体证据的基因。通过分子克隆和DNA测序对这些基因进行分析，可能会鉴定出对RNA转录起始或终止很重要的序列。导致β地中海贫血的突变继续为有关有效基因表达所必需的DNA序列性质的信息提供丰富来源。通过对地中海贫血患者的研究，对正常mRNA代谢有了新的认识。
