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. 1988 May;42(5):735–741.

An extensive search for RFLP in the human glucose-6-phosphate dehydrogenase locus has revealed a silent mutation in the coding sequence.

M D'Urso 1, L Luzzatto 1, L Perroni 1, A Ciccodicola 1, G Gentile 1, I Peluso 1, M G Persico 1, T Pizzella 1, D Toniolo 1, T J Vulliamy 1
PMCID: PMC1715180  PMID: 2895981

Abstract

The genetic polymorphism of an approximately 100-kb DNA region comprising and flanking the glucose-6-phosphate dehydrogenase (G6PD) gene on human chromosome Xq28 has been analyzed in detail. By using 14 unique sequence probes and 18 restriction enzymes, we have characterized 257 restriction fragments or 370 restriction sites. On testing 12-57 individual X chromosomes, all sites but one were nonpolymorphic. However, a PstI site that maps to exon 10 of the G6PD gene, which is still monomorphic in all British and Italian subjects tested, is polymorphic in west-African people. Specifically, it is absent from 22% of Nigerian X chromosomes. By sequence analysis we have shown that the absence of this PstI site results from a G----A replacement at position 1116, corresponding to the third base of a glutamine codon; no amino acid change is produced in the protein. Thus, a polymorphic silent mutation is demonstrated in a human gene.

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Selected References

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

  1. ALLISON A. C. Glucose-6-phosphate dehydrogenase deficiency in red blood cells of East Africans. Nature. 1960 May 14;186:531–532. doi: 10.1038/186531a0. [DOI] [PubMed] [Google Scholar]
  2. Botstein D., White R. L., Skolnick M., Davis R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980 May;32(3):314–331. [PMC free article] [PubMed] [Google Scholar]
  3. Conrad M., Friedlander C., Goodman M. Evidence that natural selection acts on silent mutation. Biosystems. 1983;16(2):101–111. doi: 10.1016/0303-2647(83)90031-x. [DOI] [PubMed] [Google Scholar]
  4. Foroni L., Catovsky D., Rabbitts T. H., Luzzatto L. DNA rearrangements of immunoglobulin genes correlate with phenotypic markers in B-cell malignancies. Mol Biol Med. 1984 Feb;2(1):63–79. [PubMed] [Google Scholar]
  5. Henthorn P. S., Knoll B. J., Raducha M., Rothblum K. N., Slaughter C., Weiss M., Lafferty M. A., Fischer T., Harris H. Products of two common alleles at the locus for human placental alkaline phosphatase differ by seven amino acids. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5597–5601. doi: 10.1073/pnas.83.15.5597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hope R., Goss S., Solomon E., Ropers H. H., Banting G., Goodfellow P. N. Localization of MIC5 to the region between HPRT and G6PD on the human X chromosome. Ann Hum Genet. 1987 Jan;51(Pt 1):1–7. doi: 10.1111/j.1469-1809.1987.tb00861.x. [DOI] [PubMed] [Google Scholar]
  7. Kam W., Clauser E., Kim Y. S., Kan Y. W., Rutter W. J. Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8715–8719. doi: 10.1073/pnas.82.24.8715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Koller B. H., Orr H. T. Cloning and complete sequence of an HLA-A2 gene: analysis of two HLA-A alleles at the nucleotide level. J Immunol. 1985 Apr;134(4):2727–2733. [PubMed] [Google Scholar]
  9. Lawn R. M., Efstratiadis A., O'Connell C., Maniatis T. The nucleotide sequence of the human beta-globin gene. Cell. 1980 Oct;21(3):647–651. doi: 10.1016/0092-8674(80)90428-6. [DOI] [PubMed] [Google Scholar]
  10. Luzzatto L., Allan N. C. Relationship between the genes for glucose-6-phosphate dehydrogenase and for haemoglobin in a Nigerian population. Nature. 1968 Sep 7;219(5158):1041–1042. doi: 10.1038/2191041a0. [DOI] [PubMed] [Google Scholar]
  11. Luzzatto L., Battistuzzi G. Glucose-6-phosphate dehydrogenase. Adv Hum Genet. 1985;14:217-329, 386-8. doi: 10.1007/978-1-4615-9400-0_4. [DOI] [PubMed] [Google Scholar]
  12. Luzzatto L. Genetics of red cells and susceptibility to malaria. Blood. 1979 Nov;54(5):961–976. [PubMed] [Google Scholar]
  13. MOTULSKY A. G. Metabolic polymorphisms and the role of infectious diseases in human evolution. Hum Biol. 1960 Feb;32:28–62. [PubMed] [Google Scholar]
  14. Martini G., Toniolo D., Vulliamy T., Luzzatto L., Dono R., Viglietto G., Paonessa G., D'Urso M., Persico M. G. Structural analysis of the X-linked gene encoding human glucose 6-phosphate dehydrogenase. EMBO J. 1986 Aug;5(8):1849–1855. doi: 10.1002/j.1460-2075.1986.tb04436.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Millán J. L. Molecular cloning and sequence analysis of human placental alkaline phosphatase. J Biol Chem. 1986 Mar 5;261(7):3112–3115. [PubMed] [Google Scholar]
  16. Nukiwa T., Satoh K., Brantly M. L., Ogushi F., Fells G. A., Courtney M., Crystal R. G. Identification of a second mutation in the protein-coding sequence of the Z type alpha 1-antitrypsin gene. J Biol Chem. 1986 Dec 5;261(34):15989–15994. [PubMed] [Google Scholar]
  17. Perler F., Efstratiadis A., Lomedico P., Gilbert W., Kolodner R., Dodgson J. The evolution of genes: the chicken preproinsulin gene. Cell. 1980 Jun;20(2):555–566. doi: 10.1016/0092-8674(80)90641-8. [DOI] [PubMed] [Google Scholar]
  18. Persico M. G., Viglietto G., Martini G., Toniolo D., Paonessa G., Moscatelli C., Dono R., Vulliamy T., Luzzatto L., D'Urso M. Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5' non-coding region. Nucleic Acids Res. 1986 Mar 25;14(6):2511–2522. doi: 10.1093/nar/14.6.2511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  20. Takizawa T., Huang I. Y., Ikuta T., Yoshida A. Human glucose-6-phosphate dehydrogenase: primary structure and cDNA cloning. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4157–4161. doi: 10.1073/pnas.83.12.4157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Usanga E. A., Bienzle U., Cancedda R., Fasuan F. A., Ajayi O., Luzzatto L. Genetic variants of human erythrocyte glucose 6-phosphate dehydrogenase: new variants in West Africa characterized by column chromatography. Ann Hum Genet. 1977 Jan;40(3):279–286. doi: 10.1111/j.1469-1809.1977.tb00192.x. [DOI] [PubMed] [Google Scholar]

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