Abstract
DNA sequence analysis of a cloned partially deleted human α-thalassemia globin gene revealed a novel 3′ untranslated region displaying at least nineteen differences when compared with previously published α mRNA sequences. Restriction enzyme mapping established the origin of the α-thalassemia gene as the more 3′ of the normal, duplicated α genes (α1). DNA sequencing of a previously isolated α1 gene revealed a 3′ untranslated region identical to that of the α-thalassemia gene. The sequence of the corresponding region of the more 5′ α gene (α2) was consistent with published mRNA sequences except in three probably polymorphic positions. Therefore the 3′ untranslated regions of the highly homologous α-globin genes differ significantly. The recognition that the duplicate α genes differ in a region expressed in mature mRNA should now permit direct assessment of relative gene output in various normal and pathologic states. The divergence of the α 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.
Published Version
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