Michelson A M, Orkin S H
Cell. 1980 Nov;22(2 Pt 2):371-7. doi: 10.1016/0092-8674(80)90347-5.
DNA sequence analysis of a cloned partially deleted human alpha-thalassemia globin gene revealed a novel 3' untranslated region displaying at least nineteen differences when compared with previously published alpha mRNA sequences. Restriction enzyme mapping established the origin of the alpha-thalassemia gene as the more 3' of the normal, duplicated alpha genes (alpha 1). DNA sequencing of a previously isolated alpha 1 gene revealed a 3' untranslated region identical to that of the alpha-thalassemia gene. The sequence of the corresponding region of the more 5' alpha gene (alpha 2) was consistent with published mRNA sequences except in three probably polymorphic positions. Therefore the 3' untranslated regions of the highly homologous alpha-globin genes differ significantly. The recognition that the duplicated alpha genes differ in a region expressed in mature mRNA should not permit direct assessment of relative gene output in various normal and pathologic states. The divergence of the alpha gene 3' untranslated regions in the face of minimal coding sequence differences must be reconciled with current models for matching homologous gene sequences by recombination events.
对一个克隆的部分缺失的人类α-地中海贫血珠蛋白基因进行DNA序列分析，结果显示，与先前发表的α mRNA序列相比，其新的3'非翻译区至少有19处差异。限制性内切酶图谱分析确定该α-地中海贫血基因起源于正常的、重复的α基因（α1）中更靠3'端的那个基因。对先前分离的α1基因进行DNA测序，结果显示其3'非翻译区与α-地中海贫血基因的3'非翻译区相同。更靠5'端的α基因（α2）相应区域的序列，除了三个可能的多态性位点外，与已发表的mRNA序列一致。因此，高度同源的α-珠蛋白基因的3'非翻译区存在显著差异。认识到重复的α基因在成熟mRNA中表达的区域存在差异，不应直接用于评估各种正常和病理状态下相对基因的输出情况。面对最小的编码序列差异，α基因3'非翻译区的分歧必须与当前通过重组事件匹配同源基因序列的模型相协调。
