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. 1988 Nov;85(22):8683–8687. doi: 10.1073/pnas.85.22.8683

Physical linkage of the genes for platelet membrane glycoproteins IIb and IIIa.

P F Bray 1, G Barsh 1, J P Rosa 1, X Y Luo 1, E Magenis 1, M A Shuman 1
PMCID: PMC282524  PMID: 3186752

Abstract

The fibrinogen receptor on human platelets is a prototypic member of the integrin family and is composed of subunit glycoproteins IIb (gpIIb) and IIIa (gpIIIa) in a 1:1 stoichiometric ratio. We have isolated cDNA clones for gpIIb and gpIIIa and localized both genes to chromosome 17. In the current study, several approaches were used to localize and map the genes for gpIIb and gpIIIa. A preliminary evaluation of subchromosomal localization was performed by using a panel of mouse-human somatic cell hybrids that contain different amounts of the long arm of human chromosome 17. Southern hybridization to the DNA of these hybrids shows that both genes map near the thymidine kinase gene. In situ hybridization to intact human chromosomes localized both genes to the 17q21-22 region. To better define the physical distance between the two genes, we examined the genomic hybridization pattern of each cDNA probe to high molecular weight restriction fragments separated by pulsed-field gel electrophoresis. Serial hybridizations of the same filter have allowed construction of long-range Mlu I and Sfi I restriction maps spanning more than 500 kilobases. Finally, nonoverlapping portions of the cDNAs for both gpIIb and gpIIIa were used to probe Sfi I digests of genomic DNA separated by field-inversion gels. This confirmed that the genes are physically linked within the same 260-kilobase Sfi I fragment and suggests that the gene for gpIIb is located on the 3' side of the gene for gpIIIa. These results suggest that coordinate expression of gpIIb and gpIIIa may depend on physical proximity.

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Selected References

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

  1. Barlow D. P., Bućan M., Lehrach H., Hogan B. L., Gough N. M. Close genetic and physical linkage between the murine haemopoietic growth factor genes GM-CSF and Multi-CSF (IL3). EMBO J. 1987 Mar;6(3):617–623. doi: 10.1002/j.1460-2075.1987.tb04799.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bray P. F., Rosa J. P., Johnston G. I., Shiu D. T., Cook R. G., Lau C., Kan Y. W., McEver R. P., Shuman M. A. Platelet glycoprotein IIb. Chromosomal localization and tissue expression. J Clin Invest. 1987 Dec;80(6):1812–1817. doi: 10.1172/JCI113277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bray P. F., Rosa J. P., Lingappa V. R., Kan Y. W., McEver R. P., Shuman M. A. Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1480–1484. doi: 10.1073/pnas.83.5.1480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown W. R., Bird A. P. Long-range restriction site mapping of mammalian genomic DNA. 1986 Jul 31-Aug 6Nature. 322(6078):477–481. doi: 10.1038/322477a0. [DOI] [PubMed] [Google Scholar]
  5. Burke D. T., Carle G. F., Olson M. V. Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science. 1987 May 15;236(4803):806–812. doi: 10.1126/science.3033825. [DOI] [PubMed] [Google Scholar]
  6. Carle G. F., Frank M., Olson M. V. Electrophoretic separations of large DNA molecules by periodic inversion of the electric field. Science. 1986 Apr 4;232(4746):65–68. doi: 10.1126/science.3952500. [DOI] [PubMed] [Google Scholar]
  7. Church R. L., SundarRaj N., McDougall J. K. Regional chromosome mapping of the human skin type I procollagen gene using adenovirus 12-fragmentation of human-mouse somatic cell hybrids. Cytogenet Cell Genet. 1980;27(1):24–30. doi: 10.1159/000131460. [DOI] [PubMed] [Google Scholar]
  8. Courtois G., Morgan J. G., Campbell L. A., Fourel G., Crabtree G. R. Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters. Science. 1987 Oct 30;238(4827):688–692. doi: 10.1126/science.3499668. [DOI] [PubMed] [Google Scholar]
  9. Créau-Goldberg N., Turleau C., Cochet C., Huerre C., Junien C., de Grouchy J. Conservation of the human COL1A1-TK-GAA synteny and homoeologous assignment in the African green monkey and the baboon (Cercopithecoidae). Hum Genet. 1984;68(4):333–336. doi: 10.1007/BF00292595. [DOI] [PubMed] [Google Scholar]
  10. Elsevier S. M., Kucherlapati R. S., Nichols E. A., Creagan R. P., Giles R. E., Ruddle F. H., Willecke K., McDougall J. K. Assignment of the gene for galactokinase to human chromosome 17 and its regional localisation to band q21-22. Nature. 1974 Oct 18;251(5476):633–636. doi: 10.1038/251633a0. [DOI] [PubMed] [Google Scholar]
  11. Fitzgerald L. A., Steiner B., Rall S. C., Jr, Lo S. S., Phillips D. R. Protein sequence of endothelial glycoprotein IIIa derived from a cDNA clone. Identity with platelet glycoprotein IIIa and similarity to "integrin". J Biol Chem. 1987 Mar 25;262(9):3936–3939. [PubMed] [Google Scholar]
  12. Ginsberg M. H., Lightsey A., Kunicki T. J., Kaufmann A., Marguerie G., Plow E. F. Divalent cation regulation of the surface orientation of platelet membrane glycoprotein IIb. Correlation with fibrinogen binding function and definition of a novel variant of Glanzmann's thrombasthenia. J Clin Invest. 1986 Oct;78(4):1103–1111. doi: 10.1172/JCI112667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Grayson D. R., Costa R. H., Xanthopoulos K. G., Darnell J. E. One factor recognizes the liver-specific enhancers in alpha 1-antitrypsin and transthyretin genes. Science. 1988 Feb 12;239(4841 Pt 1):786–788. doi: 10.1126/science.3257586. [DOI] [PubMed] [Google Scholar]
  14. Hardy D. A., Bell J. I., Long E. O., Lindsten T., McDevitt H. O. Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis. Nature. 1986 Oct 2;323(6087):453–455. doi: 10.1038/323453a0. [DOI] [PubMed] [Google Scholar]
  15. Harper M. E., Saunders G. F. Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization. Chromosoma. 1981;83(3):431–439. doi: 10.1007/BF00327364. [DOI] [PubMed] [Google Scholar]
  16. Herrmann B. G., Barlow D. P., Lehrach H. A large inverted duplication allows homologous recombination between chromosomes heterozygous for the proximal t complex inversion. Cell. 1987 Mar 13;48(5):813–825. doi: 10.1016/0092-8674(87)90078-x. [DOI] [PubMed] [Google Scholar]
  17. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  18. Jennings L. K., Phillips D. R. Purification of glycoproteins IIb and III from human platelet plasma membranes and characterization of a calcium-dependent glycoprotein IIb-III complex. J Biol Chem. 1982 Sep 10;257(17):10458–10466. [PubMed] [Google Scholar]
  19. Kunicki T. J., Pidard D., Rosa J. P., Nurden A. T. The formation of Ca++-dependent complexes of platelet membrane glycoproteins IIb and IIIa in solution as determined by crossed immunoelectrophoresis. Blood. 1981 Aug;58(2):268–278. [PubMed] [Google Scholar]
  20. Magenis R. E., Donlon T. A., Tomar D. R. Localization of the beta-globin gene to 11p15 by in situ hybridization: utilization of chromosome 11 rearrangements. Hum Genet. 1985;69(4):300–303. doi: 10.1007/BF00291645. [DOI] [PubMed] [Google Scholar]
  21. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  22. Marlin S. D., Morton C. C., Anderson D. C., Springer T. A. LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells. J Exp Med. 1986 Sep 1;164(3):855–867. doi: 10.1084/jem.164.3.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Münke M., Francke U. The physical map of Mus musculus chromosome 11 reveals evolutionary relationships with different syntenic groups of genes in Homo sapiens. J Mol Evol. 1987;25(2):134–140. doi: 10.1007/BF02101755. [DOI] [PubMed] [Google Scholar]
  24. Nelson C., Albert V. R., Elsholtz H. P., Lu L. I., Rosenfeld M. G. Activation of cell-specific expression of rat growth hormone and prolactin genes by a common transcription factor. Science. 1988 Mar 18;239(4846):1400–1405. doi: 10.1126/science.2831625. [DOI] [PubMed] [Google Scholar]
  25. Nurden A. T., Caen J. P. An abnormal platelet glycoprotein pattern in three cases of Glanzmann's thrombasthenia. Br J Haematol. 1974 Oct;28(2):253–260. doi: 10.1111/j.1365-2141.1974.tb06660.x. [DOI] [PubMed] [Google Scholar]
  26. Nurden A. T., Rosa J. P., Fournier D., Legrand C., Didry D., Parquet A., Pidard D. A variant of Glanzmann's thrombasthenia with abnormal glycoprotein IIb-IIIa complexes in the platelet membrane. J Clin Invest. 1987 Mar;79(3):962–969. doi: 10.1172/JCI112907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Phillips D. R., Agin P. P. Platelet membrane defects in Glanzmann's thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest. 1977 Sep;60(3):535–545. doi: 10.1172/JCI108805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Phillips D. R., Charo I. F., Parise L. V., Fitzgerald L. A. The platelet membrane glycoprotein IIb-IIIa complex. Blood. 1988 Apr;71(4):831–843. [PubMed] [Google Scholar]
  29. Poncz M., Eisman R., Heidenreich R., Silver S. M., Vilaire G., Surrey S., Schwartz E., Bennett J. S. Structure of the platelet membrane glycoprotein IIb. Homology to the alpha subunits of the vitronectin and fibronectin membrane receptors. J Biol Chem. 1987 Jun 25;262(18):8476–8482. [PubMed] [Google Scholar]
  30. Pytela R., Pierschbacher M. D., Ginsberg M. H., Plow E. F., Ruoslahti E. Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp--specific adhesion receptors. Science. 1986 Mar 28;231(4745):1559–1562. doi: 10.1126/science.2420006. [DOI] [PubMed] [Google Scholar]
  31. Retief E., Parker M. I., Retief A. E. Regional chromosome mapping of human collagen genes alpha 2(I) and alpha 1(I) (COLIA2 and COLIA1). Hum Genet. 1985;69(4):304–308. doi: 10.1007/BF00291646. [DOI] [PubMed] [Google Scholar]
  32. Rosa J. P., Bray P. F., Gayet O., Johnston G. I., Cook R. G., Jackson K. W., Shuman M. A., McEver R. P. Cloning of glycoprotein IIIa cDNA from human erythroleukemia cells and localization of the gene to chromosome 17. Blood. 1988 Aug;72(2):593–600. [PubMed] [Google Scholar]
  33. Sheer D., Sheppard D. M., le Beau M., Rowley J. D., San Roman C., Solomon E. Localization of the oncogene c-erbA1 immediately proximal to the acute promyelocytic leukaemia breakpoint on chromosome 17. Ann Hum Genet. 1985 Jul;49(Pt 3):167–171. doi: 10.1111/j.1469-1809.1985.tb01690.x. [DOI] [PubMed] [Google Scholar]
  34. Sosnoski D. M., Emanuel B. S., Hawkins A. L., van Tuinen P., Ledbetter D. H., Nussbaum R. L., Kaos F. T., Schwartz E., Phillips D., Bennett J. S. Chromosomal localization of the genes for the vitronectin and fibronectin receptors alpha subunits and for platelet glycoproteins IIb and IIIa. J Clin Invest. 1988 Jun;81(6):1993–1998. doi: 10.1172/JCI113548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weisbrod S. Active chromatin. Nature. 1982 May 27;297(5864):289–295. doi: 10.1038/297289a0. [DOI] [PubMed] [Google Scholar]
  36. Yang Y. C., Kovacic S., Kriz R., Wolf S., Clark S. C., Wellems T. E., Nienhuis A., Epstein N. The human genes for GM-CSF and IL 3 are closely linked in tandem on chromosome 5. Blood. 1988 Apr;71(4):958–961. [PubMed] [Google Scholar]

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