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. 1979 Nov 10;7(5):1147–1162. doi: 10.1093/nar/7.5.1147

Isolation and characterization of cloned human fetal globin genes.

F Ramirez, A L Burns, J G Mears, S Spence, D Starkman, A Bank
PMCID: PMC342293  PMID: 514810

Abstract

Three clones containing both the human G gamma and A gamma globlin genes have been isolated and characterized from a library of DNA fragments generated by partial Eco RI digestion of cellular DNA using charon 4A phage as vector. Two of the clones (NY 2 and 3) are identical and have an insert of 14.0 kb. The third clone (NY 1) has a 15.4 kb insert by virtue of an extra 1.4 kb Eco RI fragment at its 5' most end. This clone also has a Kpn I site not present in the other two suggesting it is the product of the gamma gene on the opposite chromosome. Restriction analysis of the three clones indicates that the G gamma and A gamma genes are linked on a single continuous piece of DNA and are separated by 3.5 kb and each contains at least one large intervening sequence of 0.85 kg between the Bam HI and Eco RI sites. These findings in cloned DNA provide direct evidence for linkage and organization of the gamma genes in man.

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Selected References

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

  1. Bank A., Ramirez F. The molecular biology of the thalassemia syndromes. CRC Crit Rev Biochem. 1978;5(4):343–367. doi: 10.3109/10409237809177146. [DOI] [PubMed] [Google Scholar]
  2. Deisseroth A., Nienhuis A., Lawrence J., Giles R., Turner P., Ruddle F. H. Chromosomal localization of human beta globin gene on human chromosome 11 in somatic cell hybrids. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1456–1460. doi: 10.1073/pnas.75.3.1456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Flavell R. A., Kooter J. M., De Boer E., Little P. F., Williamson R. Analysis of the beta-delta-globin gene loci in normal and Hb Lepore DNA: direct determination of gene linkage and intergene distance. Cell. 1978 Sep;15(1):25–41. doi: 10.1016/0092-8674(78)90080-6. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Lawn R. M., Fritsch E. F., Parker R. C., Blake G., Maniatis T. The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA. Cell. 1978 Dec;15(4):1157–1174. doi: 10.1016/0092-8674(78)90043-0. [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. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Smithies O., Blechl A. E., Denniston-Thompson K., Newell N., Richards J. E., Slightom J. L., Tucker P. W., Blattner F. R. Cloning human fetal gamma globin and mouse alpha-type globin DNA: characterization and partial sequencing. Science. 1978 Dec 22;202(4374):1284–1289. doi: 10.1126/science.725604. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Weinstock R., Sweet R., Weiss M., Cedar H., Axel R. Intragenic DNA spacers interrupt the ovalbumin gene. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1299–1303. doi: 10.1073/pnas.75.3.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wilson J. T., Wilson L. B., deRiel J. K., Villa-komaroff L., Efstratiadis A., Forget B. G., Weissman S. M. Insertion of synthetic copies of human globin genes into bacterial plasmids. Nucleic Acids Res. 1978 Feb;5(2):563–581. doi: 10.1093/nar/5.2.563. [DOI] [PMC free article] [PubMed] [Google Scholar]

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