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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Weatherall, D. J. & Clegg, J. B. Cell 29, 7–9 (1982).
Traeger, J., Wood, W. G., Clegg, J. B. & Weatherall, D. J. Nature 288, 497–499 (1980).
Benz, E. J. Jr et al. J. clin. Invest. 68, 118–126 (1981).
Antonarakis, S. E. et al. Proc. natn. Acad. Sci. U.S.A. 79, 6608–6611 (1982).
Maxam, A. & Gilbert, W. Meth. Enzym. 65, 499–560 (1980).
Treisman, R., Proudfoot, N. J., Shander, M. & Maniatis, T. Cell 29, 903–911 (1982).
Banerji, J., Rusconi, S. & Schaffner, W. Cell 27, 299–308 (1981).
Busslinger, M., Moschonas, N. & Flavell, R. A. Cell 27, 289–308 (1981).
Thomas, P. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980).
Weaver, R. F. & Weissmann, C. Nucleic Acids Res. 7, 1175–1193 (1979).
Breathnach, R. & Chambon, P. A. Rev. Biochem. 50, 349–383 (1981).
Mount, S. M. Nucleic Acids Res. 10, 459–472 (1982).
Felber, B. K., Orkin, S. H. & Hamer, D. H. Cell 29, 895–902 (1982).
Fukumaki, Y. et al. Cell 28, 585–593 (1982).
Traeger, J., Winichagoon, P. & Wood, W. H. J. clin. Invest. 69, 1050–1053 (1982).
Orkin, S. H. et al. Nature 296, 627–631 (1982).
Favaloro, J., Treisman, R. & Kamen, R. Meth. Enzym. 68, 718–749 (1980).
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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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