Anand R, Boehm C D, Kazazian H H, Vanin E F
Department of Biochemistry, Ohio State University, Columbus, OH 43210.
Blood. 1988 Aug;72(2):636-41.
We report the characterization of a beta zero-thalassemia in an American Black with unusually high HbA2 and HbF levels. Genomic southern analysis indicated that the individual was heterozygous for a deletion that began within the second intervening sequence of the beta-globin gene and extended approximately 1.4 kb in the 5' direction. A clone spanning the breakpoint on the abnormal chromosome was isolated and further mapped, and the deletion joint was sequenced. Comparison of the normal beta-globin gene and its 5' flanking region with the deletion joint sequence indicated that the 5' breakpoint for this deletion was 484 base pairs (bp) 5' to the transcriptional start site for the beta-globin gene and the 3' breakpoint was 908 bp into the beta-globin gene; the deletion removed a total of 1,393 bp. Comparison of the normal 5' and 3' breakpoint sequences indicated that this deletion was the result of a "clean" nonhomologous breakage and reunion event; ie, no spurious bases were added during the recombinational event. Analysis of the breakpoints of this deletion together with the breakpoints of two other small deletions involving the beta-globin gene suggests that the breakpoints may occur at DNA polymerase alpha pause sites.
我们报告了一名美国黑人β0地中海贫血的特征，其HbA2和HbF水平异常高。基因组Southern分析表明，该个体为β珠蛋白基因第二个间隔序列内开始的缺失杂合子，向5'方向延伸约1.4 kb。分离出一个跨越异常染色体断点的克隆并进一步定位，对缺失接头进行测序。将正常β珠蛋白基因及其5'侧翼区域与缺失接头序列进行比较，表明该缺失的5'断点位于β珠蛋白基因转录起始位点5'端484个碱基对（bp）处，3'断点位于β珠蛋白基因内908 bp处；该缺失共去除1393 bp。正常5'和3'断点序列的比较表明，该缺失是“干净”的非同源断裂和重聚事件的结果；即，在重组事件中未添加假碱基。对该缺失的断点以及另外两个涉及β珠蛋白基因的小缺失的断点进行分析表明，断点可能发生在DNA聚合酶α暂停位点。
