Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Partial deletion of the α-globin structural gene in human α-thalassaemia

Abstract

Defective synthesis of specific polypeptide chains of haemoglobins is the hallmark of human disorders known collectively as the thalassaemia syndromes1. Genetic lesions intimately linked to or within the globin genes are responsible for these conditions. Recently, the molecular basis of several forms of thalassaemia has been clarified by examination of the organization and structure of globin genes. Gene mapping studies using the gel blotting technique of Southern2 have revealed an array of deletions involving globin structural genes in thalassaemias3–12 and nucleotide sequencing has identified a point mutation responsible for thalassaemia in one individual13. In most α-thalassaemias, deletion of entire α-globin structural genes has been observed3,4. In specific forms of β-thalassaemia in which δ-globin chain expression is affected (δβ-thalassaemia, γδβ-thalassaemia and hereditary persistance of fetal haemoglobin syndrome), various deletions within the cluster of closely linked γ-, δ- and β-globin genes occur5–9. In some Asian Indian individuals with β°-thalassaemia, an internal deletion in the DNA involving the 3′-portion of the β-globin gene has been described10–12. Lastly, in one Chinese patient with β°-thalassaemia, a nonsense mutation within the β-sequence has been identified13. We now report a new genetic lesion present in some individuals with α-thalassaemia: an extensive deletion of the 5′ portion of the α-globin structural gene. This defect has been characterized by DNA sequence analysis of cloned α-thalassaemia genes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Weatherall, D. J. & Clegg, J. B. Cell 16, 467–479 (1979).

    Article  CAS  Google Scholar 

  2. Southern, E. M. J. molec. Biol. 98, 503–517 (1975).

    Article  CAS  Google Scholar 

  3. Orkin, S. H. et al. New Engl. J. Med. 299, 166–172 (1978).

    Article  CAS  Google Scholar 

  4. Embury, S., Lebo, R., Dozy, A. & Kan, Y. W. J. clin. Invest. 63, 1307–1310 (1979).

    Article  CAS  Google Scholar 

  5. Mears, J. G. et al. Proc. natn. Acad. Sci. U.S.A. 75, 1222–1226 (1978).

    Article  ADS  CAS  Google Scholar 

  6. Fritsch, E. F., Lawn, R. M. & Maniatis, T. Nature 279, 598–603 (1979).

    Article  ADS  CAS  Google Scholar 

  7. Orkin, S. H., Alter, B. P. & Altay, C. J. clin. Invest. 64, 866–869 (1979).

    Article  CAS  Google Scholar 

  8. Ottolenghi, S. et al. Nature 278, 654 (1979).

    Article  ADS  CAS  Google Scholar 

  9. Van der Ploeg, L. H. T., Koning, A., Oort, M., Roos, D., Bernini, L. & Flavell, R. A. Nature 283, 637–642 (1980).

    Article  ADS  CAS  Google Scholar 

  10. Flavell, R. A., Bernards, R., Kooter, J.M. & deBoer, E. Nucleic Acids Res. 6, 2749–2760 (1979).

    Article  CAS  Google Scholar 

  11. Orkin, S.H., Old, J.M., Weatherall, D.J. & Nathan, D.G. Proc. natn. Acad. Sci. U.S.A. 76, 2400–2404 (1979).

    Article  ADS  CAS  Google Scholar 

  12. Orkin, S.H., Kolodner, R., Michelson, A. & Husson, R. Proc. natn. Acad. Sci. U.S.A. (in the Press).

  13. Chang, J. C. & Kan, Y. W. Proc. natn. Acad. Sci. U.S.A. 76, 2886–2889 (1979).

    Article  ADS  CAS  Google Scholar 

  14. Orkin, S. H. Proc. natn. Acad. Sci. U.S.A. 75, 5950–5954 (1978).

    Article  ADS  CAS  Google Scholar 

  15. Orkin, S. H. et al. Cell 17, 33–42 (1979).

    Article  CAS  Google Scholar 

  16. Kan, Y. W. et al. Blood 54, 1434–1438 (1979).

    CAS  PubMed  Google Scholar 

  17. Tilghman, S. et al. Proc. natn. Acad. Sci. U.S.A. 74, 4406–4410 (1977).

    Article  ADS  CAS  Google Scholar 

  18. Blattner, F. et al. Science 202, 1279–1284 (1978).

    Article  ADS  CAS  Google Scholar 

  19. Benton, W. D. & Davis, R. W. Science 196, 180–182 (1977).

    Article  ADS  CAS  Google Scholar 

  20. Wilson, J. T. et al. Nucleic Acids Res. 5, 563–581 (1978).

    Article  CAS  Google Scholar 

  21. Blattner, F. R. et al. Science 196, 161–169 (1977).

    Article  ADS  CAS  Google Scholar 

  22. Kemp, D. J., Cory, S. & Adams, J.M. Proc. natn. Acad. Sci. U.S.A. 76, 4627–4631 (1979).

    Article  ADS  CAS  Google Scholar 

  23. Wilson, J. T. et al. J. biol. Chem. 255, 2807–2815 (1980).

    CAS  PubMed  Google Scholar 

  24. Lauer, J., Shen, C-K.J. & Maniatis, T. Cell 20, 119–130 (1980).

    Article  CAS  Google Scholar 

  25. Maxam, A. & Gilbert, W. Meth. Enzym. (in the press).

  26. Nishioka, Y. & Leder, P. Cell 18, 875–882 (1979).

    Article  CAS  Google Scholar 

  27. Goossens, M. et al. Proc. natn. Acad. Sci. U.S.A. 77, 518–521 (1980).

    Article  ADS  CAS  Google Scholar 

  28. Smith, H. O. & Birnstiel, M. L. Nucleic Acids Res. 3, 2387–2398 (1976).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orkin, S., Michelson, A. Partial deletion of the α-globin structural gene in human α-thalassaemia. Nature 286, 538–540 (1980). https://doi.org/10.1038/286538a0

Download citation

  • Received:

  • Accepted:

  • Issue date:

  • DOI: https://doi.org/10.1038/286538a0

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing