Abstract
We have examined the genetic polymorphism previously reported to be associated with the sickle-cell (beta s) gene. The polymorphism involves an alteration of the DNA sequence 3' to the beta-globin gene as detected with the restriction endonuclease, Hpa I. In normal individuals, the beta-globin gene is contained within a DNA fragment of 7.6 kilobases (kb), whereas 87% of individuals with sickle-cell anemia have been reported to have the beta s-gene associated with a 13.0-kb Hpa I fragment. We have studied this polymorphism in 31 New York Black individuals homozygous for sickle-cell anemia to ascertain its genetic and biochemical significance and to evaluate its potential use in the prenatal diagnosis of sickle-cell disease. Our results show only a 58% association of the beta s-gene and the 13.0-kb Hpa I fragment, as well as the presence of additional variants involving the Hpa I site. In addition, the 13.0-kb fragment is also found associated with the beta c- and beta A-genes. Thus, the Hpa I polymorphism probably represents a change in DNA not specifically associated with the beta s-gene, and appears to antedate the beta s-and beta c-mutations.
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- 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]
- 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]
- Kan Y. W., Dozy A. M. Antenatal diagnosis of sickle-cell anaemia by D.N.A. analysis of amniotic-fluid cells. Lancet. 1978 Oct 28;2(8096):910–912. doi: 10.1016/s0140-6736(78)91629-x. [DOI] [PubMed] [Google Scholar]
- Kan Y. W., Dozy A. M. Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5631–5635. doi: 10.1073/pnas.75.11.5631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurnit D. M. Evolution of sickle variant gene. Lancet. 1979 Jan;1(8107):104–104. doi: 10.1016/s0140-6736(79)90093-x. [DOI] [PubMed] [Google Scholar]
- Mears J. G., Ramirez F., Leibowitz D., Bank A. Organization of human delta--and beta-globin genes in cellular DNA and the presence of intragenic inserts. Cell. 1978 Sep;15(1):15–23. doi: 10.1016/0092-8674(78)90079-x. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- 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]