人类珠蛋白相关基因上游开放阅读框的变异分析

发布时间：2018-04-17 02:39

本文选题：β-地中海贫血 + 突变　；参考：《遗传》2017年03期

【摘要】：β-地中海贫血症是一种珠蛋白生成障碍的常染色体隐性遗传病。而γ珠蛋白基因的开放表达和胎儿血红蛋白的合成,是缓解β地中海贫血病人临床表型的一个重要因素。本研究针对202个血红蛋白相关调控基因或mi RNA,对1802个β-地中海贫血症患者进行了目标区域捕获测序。通过生物信息学的分析,检测出了所有捕获区域内的突变。进一步对位于5′端非编码区(5′untranslated region,5′UTR)的突变进行系统扫描,共计寻找到41个影响u ORF(upstream open reading frame,u ORF)有或无的功能性突变。从中选取了CHTOP基因(chr1:153606541 CT)和TGFB1基因(chr19:41859418 GA)的两个突变,通过定点诱变和双荧光素酶报告实验,在体外证实这两个突变均可显著地改变下游基因的表达。该研究结果为β-地中海贫血症临床表型的精确诊断提供了潜在的筛查靶点。
[Abstract]:尾-thalassemia is an autosomal recessive disorder of globin formation.The open expression of 纬 -globin gene and the synthesis of fetal hemoglobin are important factors to alleviate the clinical phenotype of 尾 -thalassemia patients.In this study, 182 尾-thalassemia patients were sequenced by targeting 202 hemoglobin related regulatory genes or mi RNAs.The mutations in all capture regions were detected by bioinformatics analysis.Furthermore, the mutations located in the 5'untranslated region (5'untranslated region) were systematically scanned. A total of 41 functional mutations affecting u ORF(upstream open reading frame ORF(upstream were found.Two mutations of CHTOP gene chr1: 153606541) and TGFB1 gene chr19: 41859418) were selected. By site-directed mutagenesis and double-luciferase report experiment, it was proved that the two mutations could significantly alter the expression of downstream genes in vitro.The results provide a potential screening target for the accurate diagnosis of the clinical phenotype of 尾-thalassemia.
【作者单位】：南方医科大学基础医学院医学遗传学教研室;
【基金】：教育部博士点基金优先资助领域重点项目(编号:20134433130001) 国家自然科学基金委员会-广东省人民政府联合基金课题(编号:U1201222)资助~~
【分类号】：R556.61

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