Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1979 Sep;64(3):866–869. doi: 10.1172/JCI109535

Deletion of the A gamma-globin gene in G gamma-delta beta-thalassemia.

S H Orkin, B P Alter, C Altay
PMCID: PMC372193  PMID: 468997

Abstract

In an individual homozygous for G gamma-delta beta-thalassemia, a physical alteration in gamma-globin gene organization was detected by restriction enzyme mapping. The data indicated that the absence of A gamma-globin chains resulted from extension of the DNA deletion from the delta beta-globin gene region into the gamma-globin gene region rather than a functional disturbance of gamma-gene expression.

Full text

PDF
866

Images in this article

867Image
on p.867
867Image
on p.867

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Forget B. G., Hillman D. G., Lazarus H., Barell E. F., Benz ej J. R., Caskey C. T., Huisman T. H., Schroeder W. A., Housman D. Absence of messenger RNA and gene DNA for beta-globin chains in hereditary persistence of fetal hemoglobin. Cell. 1976 Mar;7(3):323–329. doi: 10.1016/0092-8674(76)90161-6. [DOI] [PubMed] [Google Scholar]
  2. Fritsch E. F., Lawn R. M., Maniatis T. Characterisation of deletions which affect the expression of fetal globin genes in man. Nature. 1979 Jun 14;279(5714):598–603. doi: 10.1038/279598a0. [DOI] [PubMed] [Google Scholar]
  3. Huisman T. H., Schroeder W. A., Efremov G. D., Duma H., Mladenovski B., Hyman C. B., Rachmilewitz E. A., Bouver N., Miller A., Brodie A. The present status of the heterogeneity of fetal hemoglobin in beta-thalassemia: an attempt to unify some observations in thalassemia and related conditions. Ann N Y Acad Sci. 1974;232(0):107–124. doi: 10.1111/j.1749-6632.1974.tb20576.x. [DOI] [PubMed] [Google Scholar]
  4. Jeffreys A. J., Flavell R. A. A physical map of the DNA regions flanking the rabbit beta-globin gene. Cell. 1977 Oct;12(2):429–439. doi: 10.1016/0092-8674(77)90119-2. [DOI] [PubMed] [Google Scholar]
  5. Kan Y. W., Holland J. P., Dozy A. M., Charache S., Kazazian H. H. Deletion of the beta-globin structure gene in hereditary persistence of foetal haemoglobin. Nature. 1975 Nov 13;258(5531):162–163. doi: 10.1038/258162a0. [DOI] [PubMed] [Google Scholar]
  6. Little P. F., Flavell R. A., Kooter J. M., Annison G., Williamson R. Structure of the human fetal globin gene locus. Nature. 1979 Mar 15;278(5701):227–231. doi: 10.1038/278227a0. [DOI] [PubMed] [Google Scholar]
  7. Mears J. G., Ramirez F., Leibowitz D., Nakamura F., Bloom A., Konotey-Ahulu F., Bank A. Changes in restricted human cellular DNA fragments containing globin gene sequences in thalassemias and related disorders. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1222–1226. doi: 10.1073/pnas.75.3.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Nienhuis A. W., Benz E. J., Jr Regulation of hemoglobin synthesis during the development of the red cell. (Second of three parts). N Engl J Med. 1977 Dec 22;297(25):1371–1381. doi: 10.1056/NEJM197712222972504. [DOI] [PubMed] [Google Scholar]
  9. Orkin S. H., Alter B. P., Altay C., Mahoney M. J., Lazarus H., Hobbins J. C., Nathan D. G. Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. N Engl J Med. 1978 Jul 27;299(4):166–172. doi: 10.1056/NEJM197807272990403. [DOI] [PubMed] [Google Scholar]
  10. Orkin S. H., Old J., Lazarus H., Altay C., Gurgey A., Weatherall D. J., Nathan D. G. The molecular basis of alpha-thalassemias: frequent occurrence of dysfunctional alpha loci among non-Asians with Hb H disease. Cell. 1979 May;17(1):33–42. doi: 10.1016/0092-8674(79)90292-7. [DOI] [PubMed] [Google Scholar]
  11. Orkin S. H. The duplicated human alpha globin genes lie close together in cellular DNA. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5950–5954. doi: 10.1073/pnas.75.12.5950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ottolenghi S., Comi P., Giglioni B., Tolstoshev P., Lanyon W. G., Mitchell G. J., Williamson R., Russo G., Musumeci S., Schillro G. Delta-beta-thalassemia is due to a gene deletion. Cell. 1976 Sep;9(1):71–80. doi: 10.1016/0092-8674(76)90053-2. [DOI] [PubMed] [Google Scholar]
  13. Ramirez F., O'Donnell J. V., Marks P. A., Bank A., Musumeci S., Schilirò G., Pizzarelli G., Russo G., Luppis B., Gambino R. Abnormal or absent beta mRNA in betao Ferrara and gene deletion in delta beta thalassaemia. Nature. 1976 Oct 7;263(5577):471–475. doi: 10.1038/263471a0. [DOI] [PubMed] [Google Scholar]
  14. Reyes G. R., Piña-Camara A., Felice A. E., Gravely M. E., Huisman T. H. Delta beta-thalassemia in a Mexican family: clinical differences among homozygotes. Hemoglobin. 1978;2(6):513–529. doi: 10.3109/03630267809005353. [DOI] [PubMed] [Google Scholar]
  15. Rovera G., Magarian C., Borun T. W. Resolution of hemoglobin subunits by electrophoresis in acid urea polyacrylamide gels containing Triton X-100. Anal Biochem. 1978 Apr;85(2):506–518. doi: 10.1016/0003-2697(78)90248-8. [DOI] [PubMed] [Google Scholar]
  16. Schroeder W. A., Huisman T. H., Shelton J. R., Shelton J. B., Kleihauer E. F., Dozy A. M., Robberson B. Evidence for multiple structural genes for the gamma chain of human fetal hemoglobin. Proc Natl Acad Sci U S A. 1968 Jun;60(2):537–544. doi: 10.1073/pnas.60.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  18. Tuan D., Biro P. A., deRiel J. K., Lazarus H., Forget B. G. Restriction endonuclease mapping of the human gamma globin gene loci. Nucleic Acids Res. 1979 Jun 11;6(7):2519–2544. doi: 10.1093/nar/6.7.2519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Weatherall D. J., Clegg J. B. Hereditary persistence of fetal haemoglobin. Br J Haematol. 1975 Feb;29(2):191–198. doi: 10.1111/j.1365-2141.1975.tb01813.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES