Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Oct;71(10):3966–3970. doi: 10.1073/pnas.71.10.3966

A Limited Number of Globin Genes in Human DNA

Roberto Gambino 1,2,3, Daniel Kacian 1,2,3, Joyce O'Donnell 1,2,3, Francesco Ramirez 1,2,3, Paul A Marks 1,2,3, Arthur Bank 1,2,3
PMCID: PMC434307  PMID: 4530276

Abstract

The number of globin genes in human cells was determined by hybridizing DNA from human spleens to 3H-labeled DNA complementary to human globin mRNA. Assuming the rates of reannealing of complementary DNA and cellular DNA are similar, the extent of hybridization of complementary DNA at various ratios of cellular DNA to complementary DNA indicate that there are fewer than 10 globin gene copies per haploid human genome. An alternative analysis of the data, which introduces no assumptions concerning the relative rates of reaction of complementary DNA and cellular DNA, indicates fewer than 20 globin gene copies are present. DNA isolated from the spleen of a patient with β+ thalassemia contained a number of globin gene copies similar to that of normal DNA.

Keywords: complementary DNA, thalassemia

Full text

PDF
3967

Selected References

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

  1. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bank A., Terada M., Metafora S., Dow L., Marks P. A. In vitro synthesis of DNA components of human genes for globins. Nat New Biol. 1972 Feb 9;235(58):167–169. doi: 10.1038/newbio235167a0. [DOI] [PubMed] [Google Scholar]
  3. Benz E. J., Jr, Forget B. G. Defect in messenger RNA for human hemoglobin synthesis in beta thalassemia. J Clin Invest. 1971 Dec;50(12):2755–2760. doi: 10.1172/JCI106778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bishop J. O., Rosbash M. Reiteration frequency of duck haemoglobin genes. Nat New Biol. 1973 Feb 14;241(111):204–207. doi: 10.1038/newbio241204a0. [DOI] [PubMed] [Google Scholar]
  5. Boyer S. H., Noyes A. N., Vrablik G. R., Donaldson L. J., Schaefer E. W., Jr, Gray C. W., Thurmon T. F. Silent hemoglobin alpha genes in apes: potential source of thalassemia. Science. 1971 Jan 15;171(3967):182–185. doi: 10.1126/science.171.3967.182. [DOI] [PubMed] [Google Scholar]
  6. Britten R. J., Kohne D. E. Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms. Science. 1968 Aug 9;161(3841):529–540. doi: 10.1126/science.161.3841.529. [DOI] [PubMed] [Google Scholar]
  7. Dow L. W., Terada M., Natta C., Metafora S., Grossbard E., Marks P. A., Bank A. Globin synthesis of intact cells and activity of isolated mRNA in -thalassaemia. Nat New Biol. 1973 May 23;243(125):114–116. [PubMed] [Google Scholar]
  8. Gulati S. C., Kacian D. L., Spiegelman S. Conditions for using DNA polymerase I as an RNA-dependent DNA polymerase. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1035–1039. doi: 10.1073/pnas.71.4.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Harrison P. R., Hell A., Birnie G. D., Paul J. Evidence for single copies of globin genes in the mouse genome. Nature. 1972 Sep 22;239(5369):219–221. doi: 10.1038/239219a0. [DOI] [PubMed] [Google Scholar]
  10. Housman D., Forget B. G., Skoultchi A., Benz E. J., Jr Quantitative deficiency of chain-specific globin messenger ribonucleic acids in the thalassemia syndromes. Proc Natl Acad Sci U S A. 1973 Jun;70(6):1809–1813. doi: 10.1073/pnas.70.6.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kacian D. L., Gambino R., Dow L. W., Grossbard E., Natta C., Ramirez F., Spiegelman S., Marks P. A., Bank A. Decreased globin messenger RNA in thalassemia detected by molecular hybridization. Proc Natl Acad Sci U S A. 1973 Jun;70(6):1886–1890. doi: 10.1073/pnas.70.6.1886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kacian D. L., Spiegelman S. Use of micrococcal nuclease to monitor hybridization reactions with DNA. Anal Biochem. 1974 Apr;58(2):534–540. doi: 10.1016/0003-2697(74)90221-8. [DOI] [PubMed] [Google Scholar]
  13. Kirby K. S., Cook E. A. Isolation of deoxyribonucleic acid from mammalian tissues. Biochem J. 1967 Jul;104(1):254–257. doi: 10.1042/bj1040254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Melli M., Whitfield C., Rao K. V., Richardson M., Bishop J. O. DNA-RNA hybridization in vast DNA excess. Nat New Biol. 1971 May 5;231(18):8–12. [PubMed] [Google Scholar]
  15. Metafora S., Terada M., Dow L. W., Marks P. A., Bank A. Increased efficiency of exogenous messenger RNA translation in a Krebs ascites cell lysate. Proc Natl Acad Sci U S A. 1972 May;69(5):1299–1303. doi: 10.1073/pnas.69.5.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nienhuis A. W., Anderson W. F. Isolation and translation of hemoglobin messenger RNA from thalassemia, sickle cell anemia, and normal human reticulocytes. J Clin Invest. 1971 Nov;50(11):2458–2460. doi: 10.1172/JCI106745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Packman S., Aviv H., Ross J., Leder P. A comparison of globin genes in duck reticulocytes and liver cells. Biochem Biophys Res Commun. 1972 Nov 1;49(3):813–819. doi: 10.1016/0006-291x(72)90483-4. [DOI] [PubMed] [Google Scholar]
  18. Ross J., Aviv H., Scolnick E., Leder P. In vitro synthesis of DNA complementary to purified rabbit globin mRNA (RNA-dependent DNA polymerase-reticulocyte-hemoglobin-density gradient centrifugation-oligo(dT) primer). Proc Natl Acad Sci U S A. 1972 Jan;69(1):264–268. doi: 10.1073/pnas.69.1.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ross J., Ikawa Y., Leder P. Globin messenger-RNA induction during erythroid differentiation of cultured leukemia cells. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3620–3623. doi: 10.1073/pnas.69.12.3620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Straus N. A., Bonner T. I. Temperature dependence of RNA-DNA hybridization kinetics. Biochim Biophys Acta. 1972 Aug 16;277(1):87–95. doi: 10.1016/0005-2787(72)90355-3. [DOI] [PubMed] [Google Scholar]
  22. Verma I. M., Temple G. F., Fan H., Baltimore D. In vitro synthesis of DNA complementary to rabbit reticulocyte 10S RNA. Nat New Biol. 1972 Feb 9;235(58):163–167. doi: 10.1038/newbio235163a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES