摘要
应用双链ＤＮＡ循环测序法，对中国人群中２０例血液学正常个体，７７例β－珠蛋白合成异常患者（４３例）及其部分亲属（３４例）的β珠蛋白基因上游－５３０基序进行了序列分析。结果表明，中国人－５３０基序存在（ＡＴ）＿８Ｔ＿５、（ＡＴ）７＿Ｔ＿７和（ＡＴ）９＿Ｔ＿５三种主要的重排类型，以及一种未见报道的稀有重排类型（ＡＴ）＿（１０）Ｔ＿３。进一步经家系连锁分析，获得由β珠蛋白结构基因与－５３０基序重排组成的单体型，结果显示ＩＶＳ－ＩＩ－６５４（Ｃ→Ｔ），ＣＤ４１－４２（－４ｂｐ）和ＨｂＥ等类型的β珠蛋白突变基因分别与（ＡＴ）＿８Ｔ＿５、（ＡＴ）＿７Ｔ＿７和（ＡＴ）＿９Ｔ＿５重排存在着连锁不平衡现象。
The repeated purine-pyrimidine motif (AT)_xT_y at the region-530bp5'to the β-globin gene is regarded as the binding site for BP1, a transcriptionally repressive nuclear protein. In present study, the rearrangement patterns of the -530 motif in the Chinese population,induding 43 patients with various hemoglobinopathies and part of their relatives (34),as well as 20 hematologically normal individuals, were investigated with the method of ds-DNA cycle sequencing. The results showed that the -530 motif in Chinese people had three major variation types-(AT)8T5,(AT)7T7 and (AT)9T5. Besides,a novel rearrangement type, (AT)10T3, was found in a hematologically normal family. Furthermore,the analysis of haplotype between the β-globin structural loci and the-530 motif rearrangement indicated that linkage disequilibrium existed between three mutant β-globin genes (i.e., IVS-Ⅱ-654 (C→T), CD41-42 (-4bp)and HbE),and three-530 motif rearrangement types (i.e., (AT)8T5, (AT)7T7 nd (AT)9T5),respectively.
基金
国家自然科学基金
卫生部医学科学基金
