Gonzalez-Redondo J M, Brickner H E, Atweh G F
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Biochem Biophys Res Commun. 1989 Aug 30;163(1):8-13. doi: 10.1016/0006-291x(89)92090-1.
Hemoglobin Malay (alpha 2 beta 2 19 Asn----Ser) has been observed in a few Malaysian patients with thalassemia intermedia. The beta Malay substitution increases the homology of the cryptic splice site at codons 17/18/19 of the beta-globin gene to the donor consensus splice sequence, suggesting that the beta-thalassemia associated with this mutation may be due to the generation of a new splice site. To test this hypothesis, we constructed a hybrid gene where we replaced part of a normal beta-globin gene with a PCR amplified region of the beta Malay gene. The expression of this mutant gene was studied in a heterologous transient expression system. The data show that nearly 25% of globin mRNA produced by this gene is abnormally spliced at the new splice site, providing a molecular mechanism for the beta-thalassemia associated with the mutation.
在一些中度地中海贫血的马来西亚患者中观察到了血红蛋白马来型（α2β2 19位天冬酰胺突变为丝氨酸）。β马来型的替代增加了β珠蛋白基因第17/18/19密码子处隐蔽剪接位点与供体共有剪接序列的同源性，这表明与该突变相关的β地中海贫血可能是由于产生了一个新的剪接位点。为了验证这一假设，我们构建了一个杂合基因，用β马来型基因的PCR扩增区域替换了正常β珠蛋白基因的一部分。在异源瞬时表达系统中研究了该突变基因的表达。数据显示，该基因产生的球蛋白mRNA中近25%在新的剪接位点处发生异常剪接，为与该突变相关的β地中海贫血提供了分子机制。
