Abstract
Glycoprotein Ibalpha (GP Ibα; CD 42b; hereafter GPIBA) is a component of the cell surface receptor for the von Willebrand factor (vWf) on platelets. Immunizations against various platelet surface antigens play a major role in neonatal alloimmune thrombocytopenia and in post-transfusion purpura. Only one antigenic polymorphism in GPIBA has thus far been established: the HPA-2 (Ko) alloantigen system. To screen other polymorphisms in GPIBA systematically, we analyzed the whole coding sequence of theGPIBA gene in 50 Finnish blood donors using the single-strand conformation polymorphism method. In addition to the known polymorphisms, we detected three others. Sequencing of the gene segments carrying the new polymorphisms revealed that none of them changed the predicted amino acid sequence. Polymorphism designatedRS was located five base pairs upstream from the initiation codon at position 3064 and had the gene frequency of 16% forR and 84% forS, respectively, in the Finnish population, and it was detectable by the restriction enzymeHae III. TheEF polymorphism was at position 3842 (Asn242) and the gene frequencies were 97% forE and 3% forF. TheKL polymorphism was at position 4142 (Arg342) and the gene frequencies were 98% forK and 2% forL. The five polymorphic positions in GPIBA formed altogether six different alleles of the gene. The data suggest that there are only a few variable amino acids in GPIBA.
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References
Bizzaro, N. and Dianese, G. Neonatal alloimmune amegakaryocytosis.Vox Sang 54: 112–114, 1988
Clemetson, K. J., McGregor, J. L., James, E., Dechavanne, M., and Lucher, E. Characterization of the platelet membrane glycoprotein abnormalities in Bernard-Soulier syndrome and comparison with normal by surface-labeling techniques and high-resolution two-dimensional gel electrophoresis.J Clin Invest 70: 304–311, 1982
Fan, E., Levin, D. B., Glickman, B. W., and Logan, D. M. Limitations in the use of SSCP analysis.Mutat Res 288: 85–92, 1993
Forrest, S., Cotton, R., Landegren, U., and Southern, E. How to find all those mutations.Nat Genet 10: 375–376, 1995
Glavac, D. and Dean, M. Optimization of the single-strand conformation polymorphism (SSCP) technique for detection of point mutations.Hum Mutat 2: 404–414, 1993
Hayashi, K. and Yandell, D. W. How sensitive is PCR-SSCP?.Hum Mutat 2: 338–346, 1993.
Ishida, F., Furihata, K., Ishida, K., Yan, J., Kitano, K., Kiyosawa, K., Furuta, S. The largest variant of platelet glycoprotein Ibα has four tandem repeats of 13 amino acids in the macroglycopeptide region and genetic linkage with methionine145.Blood 86: 1356–1360, 1995
Kekomäki, S., Partanen, J., and Kekomäki, R. Platelet alloantigens HPA-1,-2,-3,-5, and-6b.Finns Transfus Med: 193–198, 1995
Kozak, M. An analysis of 5′-noncoding sequences from 699 vertebrate messenger RNAs.Nucleic Acid Res 15: 8125–8148, 1987
Kujipers, R. W. A. M., Ouwehand, W. H., Bleeker, P. M. M., Christie, D., and von dem Borne, A. E. G. Kr. Localization of the platelet-specific HPA-2 (Ko) alloantigens on the N-terminal globular fragment of platelet glycoprotein Ibα.Blood 79: 283–288, 1992a
Kuijpers, R. W. A. M., Faber, N. M., Cuypers, H. T. M., Ouwehand, W. H., and von dem Borne, A. E. G. Kr. NH2-terminal globular domain of human platelet glycoprotein Ibα has a methionine/threonine amino acid polymorphism, which is associated with the HPA-2 (Ko) alloantigens.J Clin Invest 89: 381–384, 1992b
Leren, T. P., Solberg, K., Rodningen, O. K., Ose, L., Tonstad, S., and Berg, K. Evaluation of running conditions for SSCP analysis: application of SSCP for detection of point mutations in the LDL receptor gene.PCR Meth Appl 3: 159–162, 1993
Lopez, J. A. The platelet glycoprotein Ib-IX complex.Blood Coagulat Fibrinol 5: 97–119, 1994.
Lopez, J. A., Chung, D. W., Fujikawa, K., Hagen, F. S., Papayannopoulou, T., Roth, G. J. Cloning of the α chain of human platelet glycoprotein Ib: a transmembrane protein with homology to leucine-rich α2-glycoprotein.Proc Natl Acad Sci USA 84: 5615–5619, 1987
Lopez, J. A., Leung, B., Reynolds, C. C., Li, C. Q., and Fox, J. E. B. Efficient plasma membrane expression of a functional platelet glycoprotein Ib-IX complex requires the presence of its three subunits.J Biol Chem 267: 12851–12859, 1992a
Lopez, J. A., Ludwig, E. H., and McCarthy, B. J. Polymorphism of human glycoprotein Ibα results from a variable number of tandem repeats of a 13-amino acid sequence in the mucin-like macroglycopeptide region.J Biol Chem 267: 10055–10061, 1992b
Meyer, M. and Schellenberg, I. Platelet membrane glycoprotein Ib: genetic polymorphism detected in the intact molecule and in proteolytic fragments.Thromb Res 58: 233–242, 1990
Miller, J. L., Cunningham, D., Lyle, V. A., and Finch, C. N. Mutation in the gene encoding the α chain of platelet glycoprotein Ib in platelet-type von Willebrand disease.Proc Natl Acad Sci USA 88: 4761–4765, 1991
Miller, A. S., Dykes, D. D., and Polesky, H. F. A simple salting out procedure for extracting DNA from human nucleated cells.Nucleic Acid Res 16: 1215, 1988
Moroi, M., Jung, S. M., and Yoshida, N. Genetic polymorphism of platelet glycoprotein Ib.Blood 64: 622–629, 1984
Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K., and Sekiya, T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms.Proc Natl Acad Sci USA 8: 2766–2770, 1989
Saji, H., Maruya, E., Fuji, H., Maekawa, T., Akiyama, Y., Matsuura, T., and Hosoi, T. New platelet antigen, Siba, involved in platelet transfusion refractoriness in a Japanese man.Vox Sang 56: 283–287, 1989
Sheffield, V. C., Beck, J. S., Kwitek, A. E., Sandstöm, D. W., and Stone, E. M. The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitution.Genomics 16: 325–332, 1993
Simsek, S., Admiraal, L. G., Modderman, P. W., van der Schoot, C. E., and von dem Borne, A. E. G. Kr. Identification of a homozygous single base pair deletion in the gene coding for the platelet glycoprotein Ibα causing Bernard-Soulier syndrome.Thromb Haemost 72: 129–141, 1994a
Simsek, S., Bleeker, P. M. M., van der Schoot, C. E., and von dem Borne, A. E. G. Kr. Association of a variable number of tandem repeats (VNTR) in glycoprotein Ibα and HPA-2 alloantigens.Thromb Haemost 72: 757–761, 1994b
Van der Weerdt, Ch. M., van der Wiel, D., Engelfriet, C. P., and van Loghem, J. J., A new platelet antigen. Proceedings of the 8th Congress of European Society for Haematology, p. 379, Karger, Basel, 1961
Wenger, R. H., Kieffer, N., Wicki, A. N., and Clemetson, K. J. Structure of the human blood platelet membrane glycoprotein Ibα gene.Biochem Biophys Res Commun 156: 389–395, 1988
Wenger, R. H., Wicki, A. N., Kieffer, N., Adolph, S., Hameister, H., and Clemetson, K. J. The 5′ flanking region and chromosomal localization of the gene encoding human platelet membrane glycoprotein Ibα.Gene 85: 517–524, 1989
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Kaski, S., Kekomäki, R. & Partanen, J. Systematic screening for genetic polymorphism in human platelet glycoprotein Ibalpha . Immunogenetics 44, 170–176 (1996). https://doi.org/10.1007/BF02602582
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DOI: https://doi.org/10.1007/BF02602582