Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1983 Sep;35(5):1028–1033.

beta-Thalassemia due to a deletion of the nucleotide which is substituted in the beta S-globin gene.

H H Kazazian Jr, S H Orkin, C D Boehm, J P Sexton, S E Antonarakis
PMCID: PMC1685822  PMID: 6310991

Abstract

Sickle-cell anemia results from an A leads to T transversion in the second nucleotide of codon 6 of the beta-globin gene. We now report an uncommon beta-thalassemia gene that contains a deletion of this nucleotide. Thus, one mutation (GAG leads to GTG) produces sickle-cell anemia, while the other (GAG leads to GG) eliminates beta-globin production. These data establish that different alterations affecting one specific nucleotide can produce either an abnormal hemoglobin or beta-thalassemia. Moreover, the nucleotide sequence comprising codons 6-8 of the beta-globin gene appears to be particularly susceptible to mutations affecting nucleotide number.

Full text

PDF
1028

Images in this article

1030Fig. 1
on p.1030

Selected References

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

  1. Arous N., Galacteros F., Fessas P., Loukopoulos D., Blouquit Y., Komis G., Sellaye M., Boussiou M., Rosa J. Structural study of hemoglobin Knossos, beta 27 (B9) Ala leads to Ser. A new abnormal hemoglobin present as a silent beta-thalassemia. FEBS Lett. 1982 Oct 18;147(2):247–250. doi: 10.1016/0014-5793(82)81052-1. [DOI] [PubMed] [Google Scholar]
  2. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  3. Blattner F. R., Blechl A. E., Denniston-Thompson K., Faber H. E., Richards J. E., Slightom J. L., Tucker P. W., Smithies O. Cloning human fetal gamma globin and mouse alpha-type globin DNA: preparation and screening of shotgun collections. Science. 1978 Dec 22;202(4374):1279–1284. doi: 10.1126/science.725603. [DOI] [PubMed] [Google Scholar]
  4. Chang J. C., Kan Y. W. A sensitive new prenatal test for sickle-cell anemia. N Engl J Med. 1982 Jul 1;307(1):30–32. doi: 10.1056/NEJM198207013070105. [DOI] [PubMed] [Google Scholar]
  5. Chang J. C., Kan Y. W. Antenatal diagnosis of sickle cell anaemia by direct analysis of the sickle mutation. Lancet. 1981 Nov 21;2(8256):1127–1129. doi: 10.1016/s0140-6736(81)90584-5. [DOI] [PubMed] [Google Scholar]
  6. De Jong W. W., Went L. N., Bernini L. F. Haemoglobin Leiden: deletion of beta-6 or 7 glutamic acid. Nature. 1968 Nov 23;220(5169):788–790. doi: 10.1038/220788a0. [DOI] [PubMed] [Google Scholar]
  7. Efstratiadis A., Posakony J. W., Maniatis T., Lawn R. M., O'Connell C., Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M., Slightom J. L. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653–668. doi: 10.1016/0092-8674(80)90429-8. [DOI] [PubMed] [Google Scholar]
  8. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Marotta C. A., Forget B. G., Cohne-Solal M., Wilson J. T., Weissman S. M. Human beta-globin messenger RNA. I. Nucleotide sequences derived from complementary RNA. J Biol Chem. 1977 Jul 25;252(14):5019–5031. [PubMed] [Google Scholar]
  10. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  11. Orkin S. H., Goff S. C. Nonsense and frameshift mutations in beta 0-thalassemia detected in cloned beta-globin genes. J Biol Chem. 1981 Oct 10;256(19):9782–9784. [PubMed] [Google Scholar]
  12. Orkin S. H., Kazazian H. H., Jr, Antonarakis S. E., Goff S. C., Boehm C. D., Sexton J. P., Waber P. G., Giardina P. J. Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature. 1982 Apr 15;296(5858):627–631. doi: 10.1038/296627a0. [DOI] [PubMed] [Google Scholar]
  13. Orkin S. H., Kazazian H. H., Jr, Antonarakis S. E., Ostrer H., Goff S. C., Sexton J. P. Abnormal RNA processing due to the exon mutation of beta E-globin gene. Nature. 1982 Dec 23;300(5894):768–769. doi: 10.1038/300768a0. [DOI] [PubMed] [Google Scholar]
  14. Orkin S. H., Little P. F., Kazazian H. H., Jr, Boehm C. D. Improved detection of the sickle mutation by DNA analysis: application to prenatal diagnosis. N Engl J Med. 1982 Jul 1;307(1):32–36. doi: 10.1056/NEJM198207013070106. [DOI] [PubMed] [Google Scholar]
  15. Scott A. F., Phillips J. A., 3rd, Migeon B. R. DNA restriction endonuclease analysis for localization of human beta- and delta-globin genes on chromosome 11. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4563–4565. doi: 10.1073/pnas.76.9.4563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Southern E. Gel electrophoresis of restriction fragments. Methods Enzymol. 1979;68:152–176. doi: 10.1016/0076-6879(79)68011-4. [DOI] [PubMed] [Google Scholar]
  17. Spritz R. A., Jagadeeswaran P., Choudary P. V., Biro P. A., Elder J. T., deRiel J. K., Manley J. L., Gefter M. L., Forget B. G., Weissman S. M. Base substitution in an intervening sequence of a beta+-thalassemic human globin gene. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2455–2459. doi: 10.1073/pnas.78.4.2455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Weatherall D. J., Clegg J. B. Thalassemia revisited. Cell. 1982 May;29(1):7–9. doi: 10.1016/0092-8674(82)90084-8. [DOI] [PubMed] [Google Scholar]
  19. Wilson J. T., Milner P. F., Summer M. E., Nallaseth F. S., Fadel H. E., Reindollar R. H., McDonough P. G., Wilson L. B. Use of restriction endonucleases for mapping the allele for beta s-globin. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3628–3631. doi: 10.1073/pnas.79.11.3628. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES