GAMMA-DELTA-BETA-THALASSEMIA DUE TO A DENOVO MUTATION DELETING THE 5' BETA-GLOBIN GENE ACTIVATION-REGION HYPERSENSITIVE SITES
GAMMA-DELTA-BETA-THALASSEMIA DUE TO A DENOVO MUTATION DELETING THE 5' BETA-GLOBIN GENE ACTIVATION-REGION HYPERSENSITIVE SITES
复制标题
DOI：
10.1073/pnas.86.19.7470
复制
发表时间：
1989-10-01
影响因子：
11.1
通讯作者：
ALTER, BP
中科院分区：
文献类型：
--
作者：
DRISCOLL, MC;DOBKIN, CS;ALTER, BP
γ三角洲贝塔地中海贫血是一种罕见的血红蛋白生物合成障碍，其分子特征在于β-地中海贫血的部分或完全缺失。100个碱基（kb）或更大的珠蛋白基因复合体。所描述的所有突变体的共同之处是缺失了β-半乳糖苷酶基因的most-5 "序列。珠蛋白复合物我们已经使用脉冲场凝胶电泳和聚合酶链反应技术来研究患有临床γ-淀粉样蛋白的患者。三角洲贝塔地中海贫血表型该受试者在母系遗传的β-涉及染色体的珠蛋白基因e基因5 "的30 kb序列;缺失从ε的-9.5 kb延伸至-39 kb 5"。并且包括四个DNase I超敏感位点中的三个（在ε的5 "处的-10.9kb、-14.7kb和-18kb）。剩余的β序列-珠蛋白复合物，包括-6.1kb的DNase I超敏感位点和与缺失顺式的所有结构基因，在物理上是完整的，但推测是无功能的，如不表达为镰状血红蛋白的β S-珠蛋白基因的存在所证明的。先前功能性β-DNase I超敏位点的缺失珠蛋白基因复合体的发现证实了这些位点在调节珠蛋白基因表达中的重要性。
.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 .apprxeq. 30 kb of sequences 5'' to the e gene; the deletion extends form -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.