Abstract
The form of hereditary persistence of fetal haemoglobin (HPFH) that commonly occurs in black populations is an inherited disorder of haemoglobin synthesis characterized by a uniformly high level of fetal haemoglobin (HbF) synthesis in all the erythroid cells of affected adult individuals1,2. The precise molecular basis of the HPFH phenotype remains unknown, but is of great interest because of the knowledge that could be gained, through its understanding, of the mechanisms that regulate the expression of globin genes during development. The most common form of HPFH in black populations is associated with an extensive deletion that includes the normal adult (δ and β) globin genes and adjacent flanking DNA3–8. To investigate this disorder in more detail, we have cloned the DNA encompassing the region of the gene deletion in a case of HPFH and have determined the nucleotide sequence across the 5′ end point of the deletion within the non-α-globin gene complex. We report here that this end point maps at the midpoint of a member of the ‘AluI’ family of repetitive sequences located approximately 4 kilobases (kb) to the 5′ side of the δ-globin gene. Such repetitive sequences may be ‘hot spots’ of recombination, and are possibly involved in regulating gene expression.
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 Springer Link
- 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. The Thalassemia Syndromes 3rd edn (Blackwell Scientific, Oxford, 1981).
Bunn, H. F., Forget, B. G. & Ranney, H. M. Human Hemoglobins (Saunders, Philadelphia, 1977).
Kan, Y. W., Holland, J. P., Dozy, A. M., Charache, S. & Kazazian, H. H. Nature 258, 162–163 (1975).
Forget, B. G. et al. Cell 7, 323–329 (1976).
Fritsch, E. F., Lawn, R. M. & Maniatis, T. Nature 279, 598–603 (1979).
Tuan, D., Biro, P. A., deRiel, J. K., Lazarus, H. & Forget, B. G. Nucleic Acids Res. 6, 2519–2544 (1979).
Tuan, D., Murnane, M. J., deRiel, J. K. & Forget, B. G. Nature 285, 335–337 (1980).
Bernards, R. & Flavell, R. A. Nucleic Acids Res. 8, 1521–1534 (1980).
Lawn, R. M., Fritsch, E. F., Parker, R. C., Blake, G. & Maniatis, T. Cell 15, 1157–1174 (1978).
Duncan, C. et al. Proc. natn. Acad. Sci. U.S.A. 76, 5095–5099 (1979).
Duncan, C. H., Jagadeeswaran, P., Wang, R.-R. C. & Weissman, S. M. Gene 13, 185–196 (1981).
Jagadeeswaran, P. et al. in Developmental Biology Using Purified Genes, ICN–UCLA Symp. Molec. Cell Biol. XXIII (eds Brown, D. D. & Fox, C. F.) 71–84 (Academic, New York, 1981).
Fritsch, E. F., Lawn, R. M. & Maniatis, T. Cell 19, 959–972 (1980).
Fritsch, E. F., Shen, C. K. J., Lawn, R. M. & Maniatis, T. Cold Spring Harb. Symp. quant. Biol. 45, 761–776 (1981).
Huisman, T. H. J. et al. Ann. N. Y. Acad. Sci. 232, 107–124 (1974).
Woodworth-Gutai, M. Virology 109, 353–365 (1981).
Dhruva, B. R., Shenk, T. & Subramanian, K. N. Proc. natn. Acad. Sci. U.S.A. 77, 4514–4518 (1980).
Orkin, S. H. & Michelson, A. Nature 286, 538–540 (1980).
Rothstein, R. Cell 17, 185–190 (1979).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jagadeeswaran, P., Tuan, D., Forget, B. et al. A gene deletion ending at the midpoint of a repetitive DNA sequence in one form of hereditary persistence of fetal haemoglobin. Nature 296, 469–470 (1982). https://doi.org/10.1038/296469a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/296469a0
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
