Abstract
As is typical of all β-thalassaemias1, the erythroid cells of individuals with the variant haemoglobin E (α2β226Glu→Lys) exhibit a quantitative deficiency in their content of β-globin (in this case βE-globin) and its messenger RNA2,3. To determine the molecular basis of this phenotype, we have investigated the structure and expression of cloned βE-globin genes. We report here that the complete nucleotide sequence of a βE-gene revealed the expected GAG → AAG change in codon 26 but no other mutations. Expression of βE-globin genes introduced into HeLa cells revealed two abnormalities of RNA processing: slow excision of intervening sequence-1 (IVS-1) and alternative splicing into exon-1 at a cryptic donor sequence within which the codon 26 nucleotide substitution resides. These results demonstrate a disturbance in the expression of the βE-gene attributable solely to the exon mutation—a novel mechanism for gene dysfunction.
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Orkin, S., Kazazian, H., Antonarakis, S. et al. Abnormal RNA processing due to the exon mutation of βE-globin gene. Nature 300, 768–769 (1982). https://doi.org/10.1038/300768a0
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DOI: https://doi.org/10.1038/300768a0
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