Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1984 Sep 25;12(18):7023–7034. doi: 10.1093/nar/12.18.7023

Two novel arrangements of the human fetal globin genes: G gamma-G gamma and A gamma-A gamma.

P A Powers, C Altay, T H Huisman, O Smithies
PMCID: PMC320140  PMID: 6091051

Abstract

We describe two novel arrangements of the human fetal globin gene region: one chromosome with two linked A gamma genes (A gamma-A gamma) and two chromosomes with two linked G gamma genes (G gamma-G gamma). The gamma genes of these three chromosomes were cloned and the unusual 5' A gamma gene and one of the unusual 3' G gamma genes were partially sequenced. Both of these unusual genes differ from the genes normally found at their respective locations by a nucleotide substitution at the site of the single coding region difference between normal G gamma and A gamma genes. In both cases, the substitution is identical to the nucleotide found at that position in the normal neighboring gene. The unusual 3' G gamma gene also differs from normal A gamma genes at two other nucleotide positions, but both differences appear to be "private" or exclusive to this particular gene. These unusual fetal globin gene arrangements could have arisen from point mutations or from gene conversions of limited extent, the boundaries of which have been determined for all three chromosomes.

Full text

PDF
7025

Images in this article

7027Image
on p.7027

Selected References

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

  1. Baltimore D. Gene conversion: some implications for immunoglobulin genes. Cell. 1981 Jun;24(3):592–594. doi: 10.1016/0092-8674(81)90082-9. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Brimhall B., Vedvick T. S., Jones R. T., Ahern E., Palomino E., Ahern V. Haemoglobin F Port Royal (alpha2G gamma2 125 Glu leads to Ala). Br J Haematol. 1974 Jun;27(2):313–318. doi: 10.1111/j.1365-2141.1974.tb06798.x. [DOI] [PubMed] [Google Scholar]
  4. Egel R. Intergenic conversion and reiterated genes. Nature. 1981 Mar 19;290(5803):191–192. doi: 10.1038/290191a0. [DOI] [PubMed] [Google Scholar]
  5. Hohn B. In vitro packaging of lambda and cosmid DNA. Methods Enzymol. 1979;68:299–309. doi: 10.1016/0076-6879(79)68021-7. [DOI] [PubMed] [Google Scholar]
  6. Huisman T. H., Altay C. The chemical heterogeneity of the fetal hemoglobin of black newborn babies and adults: a reevaluation. Blood. 1981 Sep;58(3):491–500. [PubMed] [Google Scholar]
  7. Huisman T. H., Reese A. L., Gardiner M. B., Wilson J. B., Lam H., Reynolds A., Nagle S., Trowell P., Zeng Y. T., Huang S. Z. The occurrence of different levels of G gamma chain and of the A gamma T variant of fetal hemoglobin in newborn babies from several countries. Am J Hematol. 1983 Apr;14(2):133–148. doi: 10.1002/ajh.2830140205. [DOI] [PubMed] [Google Scholar]
  8. Huisman T. H., Reese A. L., Gravely M. E., Harris H., Wilson J. B. The synthesis of the G gamma and A gamma chains of human fetal hemoglobin in erythroid colonies cultured from peripheral blood BFUe's of normal adults and newborn and of subjects with an A gamma or a G gamma chain abnormal fetal hemoglobin. Am J Hematol. 1980;9(2):137–150. doi: 10.1002/ajh.2830090202. [DOI] [PubMed] [Google Scholar]
  9. Huisman T. H., Schroeder W. A., Felice A., Powars D., Ringelhann B. Anomaly in the gamma chain heterogeneity of the newborn. Nature. 1977 Jan 6;265(5589):63–65. doi: 10.1038/265063a0. [DOI] [PubMed] [Google Scholar]
  10. Jeffreys A. J. DNA sequence variants in the G gamma-, A gamma-, delta- and beta-globin genes of man. Cell. 1979 Sep;18(1):1–10. doi: 10.1016/0092-8674(79)90348-9. [DOI] [PubMed] [Google Scholar]
  11. Liebhaber S. A., Goossens M., Kan Y. W. Homology and concerted evolution at the alpha 1 and alpha 2 loci of human alpha-globin. Nature. 1981 Mar 5;290(5801):26–29. doi: 10.1038/290026a0. [DOI] [PubMed] [Google Scholar]
  12. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nakatsuji T., Carver J., Wilson J. B., Lam H., Reese A. L., Nagle S., Miwa S., Huisman T. H. alpha Chain and gamma chain abnormal hemoglobins in newborn babies: structural and genetic aspects. Am J Hematol. 1983 Apr;14(2):121–132. doi: 10.1002/ajh.2830140204. [DOI] [PubMed] [Google Scholar]
  14. Nakatsuji T., Ohba Y., Huisman T. H. HB F-Yamaguchi (gamma 75Thr, gamma 80Asn, gamma 136Ala) is associated with G gamma-thalassemia. Am J Hematol. 1984 Feb;16(2):189–192. doi: 10.1002/ajh.2830160212. [DOI] [PubMed] [Google Scholar]
  15. Poncz M., Solowiejczyk D., Harpel B., Mory Y., Schwartz E., Surrey S. Construction of human gene libraries from small amounts of peripheral blood: analysis of beta-like globin genes. Hemoglobin. 1982;6(1):27–36. doi: 10.3109/03630268208996930. [DOI] [PubMed] [Google Scholar]
  16. Rimm D. L., Horness D., Kucera J., Blattner F. R. Construction of coliphage lambda Charon vectors with BamHI cloning sites. Gene. 1980 Dec;12(3-4):301–309. doi: 10.1016/0378-1119(80)90113-4. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Shen S. H., Slightom J. L., Smithies O. A history of the human fetal globin gene duplication. Cell. 1981 Oct;26(2 Pt 2):191–203. doi: 10.1016/0092-8674(81)90302-0. [DOI] [PubMed] [Google Scholar]
  19. Slightom J. L., Blechl A. E., Smithies O. Human fetal G gamma- and A gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell. 1980 Oct;21(3):627–638. doi: 10.1016/0092-8674(80)90426-2. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Sukumaran P. K., Nakatsuji T., Gardiner M. B., Reese A. L., Gilman J. G., Huisman T. H. Gamma thalassemia resulting from the deletion of a gamma-globin gene. Nucleic Acids Res. 1983 Jul 11;11(13):4635–4643. [PMC free article] [PubMed] [Google Scholar]
  22. Twigg A. J., Sherratt D. Trans-complementable copy-number mutants of plasmid ColE1. Nature. 1980 Jan 10;283(5743):216–218. doi: 10.1038/283216a0. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES