Mager D L, Henthorn P S, Smithies O
Nucleic Acids Res. 1985 Sep 25;13(18):6559-75. doi: 10.1093/nar/13.18.6559.
A clone was isolated that contains the deletion junction region from an individual with a deletion associated with Chinese G gamma + (A gamma delta beta)zero thalassemia. A clone containing the normal DNA corresponding to the 3' breakpoint of this deletion was also isolated. Portions of these two clones were sequenced and compared to the region in the A gamma-globin gene where the 5' breakpoint occurs. This comparison reveals that the breakage and reunion event was nonhomologous and that it probably involved the insertion of 36-41 bases of DNA belonging to the L1 (KpnI) family of repetitive DNA. Genomic mapping revealed that the DNA on the 3' side of this deletion is closely linked in normal DNA to the 3' breakpoints of two different large deletions that are associated with hereditary persistence of fetal hemoglobin (HPFH). We cloned and mapped 35 kbp of normal DNA from this region (greater than 45 kbp downstream of the human beta-globin gene) that contains the 3' breakpoints of the Chinese thalassemia and the two HPFH deletions. An endogenous retrovirus-like element and several other repetitive sequences are located within this region. We show that the Chinese thalassemia deletion is greater than 80 kbp in length and differs in size from the two HPFH deletions by less than 6%. We also show that the Chinese thalassemia deletion is at least 40 kbp larger than several other deletions associated with a very similar phenotype.
分离出了一个克隆，它包含来自一名患有与中国Gγ+(Aγδβ)0地中海贫血相关缺失的个体的缺失连接区域。还分离出了一个包含与该缺失的3'断点相对应的正常DNA的克隆。对这两个克隆的部分进行了测序，并与Aγ-珠蛋白基因中发生5'断点的区域进行了比较。这种比较表明，断裂和重连事件是非同源的，并且可能涉及属于L1(KpnI)重复DNA家族的36 - 41个碱基的DNA插入。基因组图谱显示，该缺失3'侧的DNA在正常DNA中与两个不同的大缺失的3'断点紧密连锁，这两个大缺失与胎儿血红蛋白遗传性持续存在(HPFH)相关。我们从该区域(人类β-珠蛋白基因下游大于45 kbp)克隆并绘制了35 kbp的正常DNA图谱，该区域包含中国地中海贫血和两个HPFH缺失的3'断点。该区域内有一个内源性逆转录病毒样元件和其他几个重复序列。我们表明，中国地中海贫血缺失长度大于80 kbp，与两个HPFH缺失的大小差异小于6%。我们还表明，中国地中海贫血缺失比其他几个与非常相似表型相关的缺失至少大40 kbp。
