Abstract
Transcriptional analysis of five different cloned β-thalassaemia genes introduced into cultured mammalian cells revealed specific defects in transcription and RNA splicing. A single base change 87 base pairs to the 5′ side of the mRNA cap site significantly lowers the level of transcription and therefore appears to represent a promoter mutation. Three genes contain different single base changes in the first intervening sequence (IVS) 5′ splice site. One mutation, at IVS1 position 1, inactivates the splice site completely; the other two, at IVS I positions 5 and 6, reduce its activity. Each mutation activates the same three cryptic splice sites. The fifth gene contains a single base change within IVS2 at position 745, which results in the formation of abnormal β-globin RNA that contains an extra exon.
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References
Bunn, H. F., Forget, B. G. & Ranney, H. M. Human Hemoglobins (Saunders, Philadelphia, 1977).
Weatherall, D. J. & Clegg, J. B. The Thalassemia Syndromes (Blackwell Scientific, Oxford, 1981).
Maniatis, T., Fritsch, E. F., Lauer, J. & Lawn, R. M. A. Rev. Genet. 14, 145 (1980).
Efstratiadis, A. et al. Cell 21, 653–688 (1980).
Orkin, S. H. & Nathan, D. G. Adv. Hum. Genet. 11, 233–280 (1981).
Proudfoot, N. J., Gil, A. & Maniatis, T. Cell 31, 553–563 (1982).
Weatherall, D. J. & Clegg, J. B. Cell 29, 7–9 (1982).
Orkin, S. H. et al. Nature 296, 627–631 (1982).
Baird, M. et al. Proc. natn. Acad. Sci. U.S.A. 78, 4218–4221 (1981).
Old, J. M. et al. Cell 14, 289–298 (1978).
Benz, E. J. et al. Cell 14, 299–312 (1978).
Maquat, L. E. et al. Proc. natn. Acad. Sci. U.S.A. 77, 4287–4291 (1980).
Kantor, J. A., Turner, P. H. & Neinhuis, A. W. Cell 21, 149–157 (1980).
Maquat, L. E., Kinniburgh, A. J., Rachmilewitz, E. A. & Ross, J. Cell 27, 543–553 (1981).
Moschonas, N. et al. Nucleic Acids Res. 9, 4391–4401 (1981).
Fukumaki, Y. et al. Cell 28, 585–593 (1982).
Ley, T. J., Aragon, N. P., Pepe, G. & Neinhuis, A. Proc. natn. Acad. Sci. U.S.A. 79, 4775–4779 (1982).
Felber, B. K., Orkin, S. H. & Hamer, D. H. Cell 29, 895–902 (1982).
Treisman, R. H., Proudfoot, N. J., Shander, M. & Maniatis, T. Cell 79, 903–911 (1982).
DiMaio, D., Treisman, R. & Maniatis, T. Proc. natn. Acad. Sci. U.S.A. 79, 4030–4034. (1982).
Banerji, J., Rusconi, S. & Schaffner, W. Cell 27, 299–308 (1981).
Busslinger, M., Moschonas, N. & Flavell, R. A. Cell 27, 289–298 (1981).
Mellon, P., Parker, V., Gluzman, Y. & Maniatis, T. Cell 27, 279–288 (1981).
Lawn, R. M., Fritsch, E. F., Parker, R. C., Blake, G. & Maniatis, T. Cell 15, 1157–1174 (1978).
Dierks, P. et al. ICN-UCLA Symp. molec. cell. Biol. 23, 347–366 (1981).
Grosveld, G. C., deBoer, E., Shewmaker, C. K. & Flavell, R. A. Nature 295, 120–125 (1982).
Grosveld, G. C., Rosenthal, A. & Flavell, R. A. Nucleic Acids Res. 10, 4951–4984 (1982).
McKnight, S. L. & Kingsbury, R. Science 217, 316–324 (1982).
Benoist, C. & Chambon, P. Nature 290, 304–310 (1981).
Fromm, M. & Berg, P. J. molec. appl. Genet. 1, 457–481 (1982).
Lacy, E. & Maniatis, T. Cell 21, 545–553 (1980).
Gannon, F. et al. Nature 278, 428–434 (1979).
Poncz, M. et al. J. biol. Chem. 257, 5994–5996 (1982).
Breathnach, R., Benoist, C., O'Hare, K., Gannon, F. & Chambon, P. Proc. natn. Acad. Sci. U.S.A. 75, 4853–4857 (1978).
Dodgson, J. B. & Engel, J. D. J. biol. Chem. (submitted).
Wieringa, B., Meyer, F., Reiser, J. & Weissmann, C. Nature 301, 38–43 (1983).
Montell, C., Fisher, E. F., Caruthers, M. H. & Berk, A. J. Nature 295, 380–384 (1982).
Choi, E., Kuehl, M. & Wall, R. Nature 286, 776–779 (1980).
Seidman, J. G. & Leder, P. Nature 286, 779–783 (1980).
Solnick, D. Nature 291, 508–510 (1981).
Orkin, S. H. et al. Nature 300, 768–769 (1982).
Humphries, R. K. et al. Blood 60, 54A (1982).
Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L. & Steitz, J. A. Nature 283, 220–224 (1980).
Rogers, J. & Wall, R. Proc. natn. Acad. Sci. U.S.A. 77, 1877–1879 (1980).
Sharp, P. A. Cell 23, 643–646 (1981)
Gilbert, W. Nature 271, 501 (1978).
Seed, B. Genetic Engineering Vol. 4 (eds Setlow, J. K. & Hollander, A.) 91–102 (Plenum, New York, 1982).
Weaver, R. F. & Weissmann, C. Nucleic Acids Res. 6, 1175–1193 (1979).
Maxam, A. & Gilbert, W. Meth. Enzym. 65, 499–560 (1980).
Mount, S. M. Nucleic Acids Res. 10, 459–472 (1982).
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Treisman, R., Orkin, S. & Maniatis, T. Specific transcription and RNA splicing defects in five cloned β-thalassaemia genes. Nature 302, 591–596 (1983). https://doi.org/10.1038/302591a0
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DOI: https://doi.org/10.1038/302591a0
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