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
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Weatherall, D. J. & Clegg, J. B. Cell 16, 467–479 (1979).
Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
Orkin, S. H. et al. New Engl. J. Med. 299, 166–172 (1978).
Embury, S., Lebo, R., Dozy, A. & Kan, Y. W. J. clin. Invest. 63, 1307–1310 (1979).
Mears, J. G. et al. Proc. natn. Acad. Sci. U.S.A. 75, 1222–1226 (1978).
Fritsch, E. F., Lawn, R. M. & Maniatis, T. Nature 279, 598–603 (1979).
Orkin, S. H., Alter, B. P. & Altay, C. J. clin. Invest. 64, 866–869 (1979).
Ottolenghi, S. et al. Nature 278, 654 (1979).
Van der Ploeg, L. H. T., Koning, A., Oort, M., Roos, D., Bernini, L. & Flavell, R. A. Nature 283, 637–642 (1980).
Flavell, R. A., Bernards, R., Kooter, J.M. & deBoer, E. Nucleic Acids Res. 6, 2749–2760 (1979).
Orkin, S.H., Old, J.M., Weatherall, D.J. & Nathan, D.G. Proc. natn. Acad. Sci. U.S.A. 76, 2400–2404 (1979).
Orkin, S.H., Kolodner, R., Michelson, A. & Husson, R. Proc. natn. Acad. Sci. U.S.A. (in the Press).
Chang, J. C. & Kan, Y. W. Proc. natn. Acad. Sci. U.S.A. 76, 2886–2889 (1979).
Orkin, S. H. Proc. natn. Acad. Sci. U.S.A. 75, 5950–5954 (1978).
Orkin, S. H. et al. Cell 17, 33–42 (1979).
Kan, Y. W. et al. Blood 54, 1434–1438 (1979).
Tilghman, S. et al. Proc. natn. Acad. Sci. U.S.A. 74, 4406–4410 (1977).
Blattner, F. et al. Science 202, 1279–1284 (1978).
Benton, W. D. & Davis, R. W. Science 196, 180–182 (1977).
Wilson, J. T. et al. Nucleic Acids Res. 5, 563–581 (1978).
Blattner, F. R. et al. Science 196, 161–169 (1977).
Kemp, D. J., Cory, S. & Adams, J.M. Proc. natn. Acad. Sci. U.S.A. 76, 4627–4631 (1979).
Wilson, J. T. et al. J. biol. Chem. 255, 2807–2815 (1980).
Lauer, J., Shen, C-K.J. & Maniatis, T. Cell 20, 119–130 (1980).
Maxam, A. & Gilbert, W. Meth. Enzym. (in the press).
Nishioka, Y. & Leder, P. Cell 18, 875–882 (1979).
Goossens, M. et al. Proc. natn. Acad. Sci. U.S.A. 77, 518–521 (1980).
Smith, H. O. & Birnstiel, M. L. Nucleic Acids Res. 3, 2387–2398 (1976).
Author information
Authors and Affiliations
Rights 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
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1038/286538a0
This article is cited by
-
The levels of ?, ?, and ? chains in patients with Hb H disease
Human Genetics (1989)
-
A mutant lymphoma cell line with a defectiveThy-1 glycoprotein gene
Immunogenetics (1987)
-
Evolution of alu family repeats since the divergence of human and chimpanzee
Journal of Molecular Evolution (1985)
-
DNA polymorphism and molecular pathology of the human globin gene clusters
Human Genetics (1985)