Driscoll M C, Dobkin C S, Alter B P
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Proc Natl Acad Sci U S A. 1989 Oct;86(19):7470-4. doi: 10.1073/pnas.86.19.7470.
gamma delta beta-Thalassemia is a rare disorder of hemoglobin biosynthesis, characterized molecularly by partial or complete deletions of the beta-globin gene complex of 100 kilobases (kb) or greater. Common to all mutants described has been the deletion of the most-5' sequences of the beta-globin complex. We have used the techniques of pulsed-field gel electrophoresis and polymerase chain reaction to study a patient with a clinical gamma delta beta-thalassemia phenotype. This subject developed a de novo deletion on a maternally inherited beta-globin gene chromosome involving approximately 30 kb of sequences 5' to the epsilon gene; the deletion extends from -9.5 kb to -39 kb 5' of epsilon and includes three of the four DNase I hypersensitive sites (at -10.9 kb, -14.7 kb, and -18 kb 5' of epsilon). The remaining sequences of the beta-globin complex, including the DNase I hypersensitive sites at -6.1 kb and all structural genes in cis to the deletion are physically intact, but presumably nonfunctional, as evidenced by the presence of a beta S-globin gene that is not expressed as a sickle hemoglobin. Deletion of DNase I hypersensitive sites on a previously functional beta-globin gene complex confirms the significance of these sites in regulating globin gene expression.
γδβ地中海贫血是一种罕见的血红蛋白生物合成障碍疾病，其分子特征是β珠蛋白基因复合体出现100千碱基（kb）或更大范围的部分或完全缺失。所有已描述的突变体都有一个共同特征，即β珠蛋白复合体最5'端序列的缺失。我们运用脉冲场凝胶电泳和聚合酶链反应技术，对一名具有临床γδβ地中海贫血表型的患者进行了研究。该患者在母系遗传的β珠蛋白基因染色体上发生了一个新生缺失，涉及ε基因5'端约30 kb的序列；该缺失从ε基因5'端的-9.5 kb延伸至-39 kb，包括四个DNase I超敏位点中的三个（在ε基因5'端的-10.9 kb、-14.7 kb和-18 kb处）。β珠蛋白复合体的其余序列，包括位于-6.1 kb处的DNase I超敏位点以及与缺失序列顺式排列的所有结构基因，在物理上是完整的，但可能无功能，这一点可由未表达为镰状血红蛋白的βS珠蛋白基因的存在得到证明。先前具有功能的β珠蛋白基因复合体上DNase I超敏位点的缺失，证实了这些位点在调节珠蛋白基因表达中的重要性。
