Abstract
The common form of β thalassaemia associated with elevated haemoglobin A2 levels can be broadly classified as β+ or β0 type according to the presence or absence of β-globin chain synthesis in the homozygous state1–4. The molecular pathology of each type is heterogeneous3–9. Apart from a subgroup of Indo-Pakistani patients10, the β-globin structural gene is intact in the majority of patients with β0 thalassaemia2–4. The amount of β-globin mRNA present in the reticulocytes of these patients varies5–7: in some it is absent or barely detectable; in others, a substantial amount is present, but it is nonfunctional. We recently demonstrated that the molecular lesion in a Chinese patient with nonfunctional β-globin mRNA11,12 was due to the mutation of the normal lysine codon AAG at amino acid 17 to the amber terminator codon UAG, which prematurely terminates the β-globin chain13. In the present study we demonstrate the first example of a nonsense mutation in humans which can be suppressed in vitro by the suppressor tRNA, as has been found in other eukaryotic cells and viruses14,15.
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References
Benz, E. J., Jr Prog. Hemat. 9, 107–155 (1975).
Nienhuis, A. & Benz, E. J. New Engl. J. Med. 297, 1371–1381 (1977).
Bank, A. Blood 51, 369–384 (1978).
Temple, G. & Kan, Y. W. Progress in Pediatrics Hematology and Oncology (PSG Publishing, in the press).
Benz, E. J. Jr Nature 263, 635–636 (1976).
Benz, E. J. Jr et al. Cell 14, 299–312 (1978).
Old, J. M. et al. Cell 14, 289–298 (1978).
Ottolenghi, S. et al. Nature 266, 231–234 (1977).
Godet, J. et al. Blood 50, 463–470 (1977).
Orkin, S. H., Old, J. M., Weatherall, D. J. & Nathan, D. G. Clin. Res. 27, 463A (1979).
Kan, Y. W., Holland, J. P., Dozy, A. M. & Varmus, H. E. Proc. natn. Acad. Sci. U.S.A. 72, 5140–5144 (1975).
Temple, G. F., Chang, J. C. & Kan, Y. W. Proc. natn. Acad. Sci. U.S.A. 74, 3047–3051 (1977).
Chang, J. C. & Kan, Y. W. Proc. natn. Acad. Sci. U.S.A. 76, 2886–2889 (1979).
Capecchi, M. R., Vonder Haar, R. A., Capecchi, N. E. & Sveda, M. M. Cell 12, 371–381 (1977).
Cremer, K. J., Bodemer, M., Summers, W. P., Summers, W. C. & Gesteland, R. F. Proc. natn. Acad. Sci. U.S.A. 76, 430–434 (1979).
Pelham, H. R. B. & Jackson, R. J. Eur. J. Biochem. 67, 247–256 (1976).
Kan, Y. W., Nathan, D. G., Cividalli, G. & Frigoletto, F. Ann. N.Y. Acad. Sci. 232, 145–151 (1974).
Wilson, J. T., deRiel, J. K., Forget, B. G., Morotta, C. A. & Weissman, S. M. Nucleic Acids Res. 4, 2353–2368 (1977).
Poon, R., Kan, Y. W. & Boyer, H. W. Nucleic Acids Res. 5, 4625–4630 (1978).
Nathan, D. G., Lodish, H. F., Kan, Y. W. & Housman, D. Proc. natn. Acad. Sci. U.S.A. 68, 2514–2518 (1971).
Capecchi, M. R., Hughes, S. H. & Wahl, G. M. Cell 6, 269–277 (1975).
Gesteland, R. F. et al. Cell 7, 381–390 (1976).
Gesteland, R. F., Wills, N., Lewis, J. B. & Grodzicker, T. G. Proc natn. Acad. Sci. U.S.A. 74, 4567–4571 (1977).
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Chang, J., Temple, G., Trecartin, R. et al. Suppression of the nonsense mutation in homozygous β0 thalassaemia. Nature 281, 602–603 (1979). https://doi.org/10.1038/281602a0
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DOI: https://doi.org/10.1038/281602a0
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