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Cell. 1980 Nov;22(2 Pt 2):371-7.

The 3' untranslated regions of the duplicated human alpha-globin genes are unexpectedly divergent.


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.

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