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Russian Journal of Genetics

, Volume 43, Issue 4, pp 451–457 | Cite as

Analysis of the AluI polymorphism in intron 1 of the human coagulation factor VIII gene: A new marker for the hemophilia a carrier detection

  • V. L. Surin
  • A. V. Lukianenko
  • Yu. A. Luchinina
Human Genetics

Abstract

Frequencies of the C/T SNP alleles at position 2403 of the human coagulation factor VIII gene intron 1, containing the AluI restriction endonuclease recognition site, were examined. Genomic DNA samples for the analysis were obtained from the consulted women and their relatives from the families with hemophilia A. A total of 221 unrelated X chromosomes were studied. The two allelic variants were found with similar frequencies of T(Alu+), 0.53 and C(Alu−), 0.47. The heterozygosity index evaluated as equal to 0.50 was correlated with the experimental heterozygote number. The absence of a tight linkage between the AluI SNP and the widely used in the hemophilia A gene diagnostics HindIII polymorphism (C/T SNP at position 103 of intron 19) was demonstrated. Summarized informativity of these two markers for obligate carriers and for those detected in this study constituted 68% (32 out of 47). At the same time using one of the markers, only 40% (HindIII) and 51% (AluI) of the consulted women were informative. The new marker was used in 13 prenatal DNA diagnostics of hemophilia A. A new deletion polymorphism (del TGA, position 2281–2283 of intron 1) was described in close proximity of the AluI SNP with the frequency of about 0.05. among the five other SNP of the factor VIII gene examined (Bme18I, intron 1; HpaII, intron 13; MnlI, exon 14; Bst4CI, exon 25; and MseI, exon 26) no effective diagnostic markers were found. Only the MnlI polymorphism could be recommended for limited usage.

Keywords

Factor Viii Prime System Carrier Detection Obligate Carrier Factor Viii Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Gitschier, J., Wood, W.I., Goralka, T.M., et al., Characterization of the Human Factor VIII Gene, Nature, 1984, vol. 312, pp. 326–330.PubMedCrossRefGoogle Scholar
  2. 2.
    Lakich, D., Kazazian, H.H., Antonarakis, S.E., et al., Inversions Disrupting the Factor VIII Gene Are a Common Cause of Severe Haemophilia A, Nat. Genet., 1993, vol. 5, pp. 236–241.PubMedCrossRefGoogle Scholar
  3. 3.
    Naylor, J., Brinke, A., Hassock, S., et al., Characteristic mRNA Abnormality Found in Half the Patients with Severe Haemophilia A Is Due to Large DNA Inversions, Hum. Mol. Genet., 1993, vol. 2, pp. 1773–1778.PubMedCrossRefGoogle Scholar
  4. 4.
    Bagnall, R.D., Waseem, N., Green, P.M., et al., Recurrent Inversion Breaking Intron 1 of the Factor VIII Gene Is a Frequent Cause of Severe Hemophilia A, Blood, 2002, vol. 99, pp. 168–174.PubMedCrossRefGoogle Scholar
  5. 5.
    Lalloz, M.R., McVey, J.H., Pattinson, J.K., et al., Haemophilia A Diagnosis by Analysis of a Hypervariable Dinucleotide Repeat within the Factor VIII Gene, Lancet, 1991, vol. 338, pp. 207–211.PubMedCrossRefGoogle Scholar
  6. 6.
    Lalloz, M.R., McVey, J.H., Michaelides, K., et al., Haemophilia A Diagnosis by Analysis of a Novel Dinucleotide Tandem Repeat Sequence within the Factor VIII Gene, Br. J. Haematol., 1992, vol. 80, p. 3.Google Scholar
  7. 7.
    Kogan, S. and Gitschier, J., Mutations and a Polymorphism in the Factor VIII Gene Discovered by Denaturing Gradient Gel Electrophoresis, Proc. Natl. Acad. Sci. USA, 1990, vol. 87, pp. 2092–2096.PubMedCrossRefGoogle Scholar
  8. 8.
    Graham, J.B., Kunkel, G.R., Fowlkes, D.M., et al., The Utility of a HindIII Polymorphism of Factor VIII Examined by Rapid DNA Analysis, Br. J. Haematol., 1990, vol. 76, pp. 75–79.PubMedGoogle Scholar
  9. 9.
    Surin, V.L., Zhukova, E.L., Krutov, A.A., et al., Simple and Convenient Detection of a HindIII Polymorphic Site in Intron 19 of Factor VIII Using PCR, Nucleic Acids Res., 1990, vol. 18, p. 3432.PubMedCrossRefGoogle Scholar
  10. 10.
    Chan, V., Tong, T.M., Chan, T.P., et al., Multiple XbaI Polymorphisms for Carrier Detection and Prenatal Diagnosis of Haemophilia A, Br. J. Haematol., 1989, vol. 73, pp. 497–500.PubMedGoogle Scholar
  11. 11.
    Bowen, D.J., De Brasi, C.D., Larripa, I.B., et al., A New Polymorphism in the Human Factor VIII Gene: Implications for Linkage Analysis in Haemophilia A and for the Evolution of int22h Sequences, Br. J. Haematol., 2000, vol. 111, pp. 544–548.PubMedCrossRefGoogle Scholar
  12. 12.
    Antonarakis, S.E., Waber, P.G., Kittur, S.D., et al., Hemophilia A. Detection of Molecular Defects and of Carriers by DNA Analysis, N. Engl. J. Med., 1985, vol. 313, pp. 842–848.PubMedCrossRefGoogle Scholar
  13. 13.
    Howarth, A. and Bowen, D.J., Linkage Analysis in Haemophilia A: Simultaneous Genotyping of Two Polymorphisms of the Human Factor VIII Gene Using Induced Heteroduplex Formation, Haemophilia, 1998, vol. 4, pp. 812–819.PubMedCrossRefGoogle Scholar
  14. 14.
    Richards, B., Heilig, R., Oberle, I., et al., Rapid PCR Analysis of the St14 (DXS52) VNTR, Nucleic Acids Res., 1991, vol. 19, p. 1944.PubMedCrossRefGoogle Scholar
  15. 15.
    Kaidalova, A.I., Smimova, O.V., Surin, V.L., et al., Evaluation of Frequencies of Locus DXS52 of the Human X-Chromosome in the Moscow Population, Russ. J. Genet., 1994, vol. 30, no. 7, pp. 844–846.Google Scholar
  16. 16.
    Bowen, D.J., Haemophilia A and Haemophilia B: Molecular Insights, J. Clin. Pathol. Mol. Pathol., 2002, vol. 55, pp. 127–144.CrossRefGoogle Scholar
  17. 17.
    Mulligan, L.M., Grover, H.J., Blanchette, V.S., et al., Recombination Between the Factor VIII Gene and the DXS52 Locus Gives the Most Probable Genetic Order As Centromere-fra(X)-DXS15-DXS52-F8C-Telomere, Am. J. Med. Genet., 1987, vol. 26, pp. 751–760.PubMedCrossRefGoogle Scholar
  18. 18.
    Tagiev, A.F., Surin, V.L., Gol’tsov, A.A., et al., The Spectrum of Beta-Thalassemia Mutation in Azerbaijan, Hum. Mutat., 1993, vol. 2, pp. 152–154.PubMedCrossRefGoogle Scholar
  19. 19.
    Tizzano, E., Vencesla, A., Cornet, M., et al., Utility of a (GT) Dinucleotide Repeat in Intron 1 of the Factor 8 Gene for Haemophilia A Carrier Diagnosis, Haemophilia, 2005, vol. 11, pp. 142–144.PubMedCrossRefGoogle Scholar
  20. 20.
    Kim, J.W., Park, S.Y., Kim, Y.M., et al., Identification of New Dinucleotide-Repeat Polymorphisms in Factor VIII Gene Using Fluorescent PCR, Haemophilia, 2005, vol. 11, pp. 38–42.PubMedCrossRefGoogle Scholar
  21. 21.
    Krawczak, M. and Cooper, D.N., Gene Deletions Causing Human Genetic Disease: Mechanism of Mutagenesis and the Role of the Local DNA Sequence Environment, Hum. Genet., 1991, vol. 86, pp. 425–441.PubMedCrossRefGoogle Scholar
  22. 22.
    Wion, K.L., Tuddenham, E.G., and Lawn, R.M., A New Polymorphism in the Factor VIII Gene for Prenatal Diagnosis of Hemophilia A, Nucleic Acids Res., 1986, vol. 14, pp. 4535–4542.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2007

Authors and Affiliations

  • V. L. Surin
    • 1
  • A. V. Lukianenko
    • 1
  • Yu. A. Luchinina
    • 1
  1. 1.Hematological Research CenterRussian Academy of Medical SciencesMoscowRussia

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