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. 1987 Apr;79(4):1204–1209. doi: 10.1172/JCI112938

Hemophilia B (Christmas disease) variants and carrier detection analyzed by DNA probes.

M C Poon, D H Chui, M Patterson, D M Starozik, L S Dimnik, D I Hoar
PMCID: PMC424311  PMID: 2881949

Abstract

We have used two strategies to study 14 hemophilia B families from 11 kindreds for possible carrier detection and prenatal diagnosis. First, we sequentially used the Factor IX probes (sequentially with restriction enzymes Taq I, Xmn I, and Dde I), and the linked probes p45h (Taq I), p45d (Pst I), and 52a (Taq I) for restriction fragment length polymorphism (RFLP) analysis. Second, we searched for useful variant Taq I digestion fragments using the Factor IX complementary DNA. Two separate new Taq I variants in exon VIII were identified. Using both strategies, 11 of 14 families (from 9 of 11 kindreds) were informative for further studies. In five kindreds studied in detail, the carrier status of all 11 at risk females was determined and prenatal diagnosis could be offered to the offsprings of each of the six carriers identified. Thus, in this study, we have identified a higher proportion of informative families than has previously been reported.

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Selected References

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

  1. Anson D. S., Choo K. H., Rees D. J., Giannelli F., Gould K., Huddleston J. A., Brownlee G. G. The gene structure of human anti-haemophilic factor IX. EMBO J. 1984 May;3(5):1053–1060. doi: 10.1002/j.1460-2075.1984.tb01926.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barker D., Schafer M., White R. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell. 1984 Jan;36(1):131–138. doi: 10.1016/0092-8674(84)90081-3. [DOI] [PubMed] [Google Scholar]
  3. Bernardi F., del Senno L., Barbieri R., Buzzoni D., Gambari R., Marchetti G., Conconi F., Panicucci F., Positano M., Pitruzzello S. Gene deletion in an Italian haemophilia B subject. J Med Genet. 1985 Aug;22(4):305–307. doi: 10.1136/jmg.22.4.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Camerino G., Oberlé I., Drayna D., Mandel J. L. A new MspI restriction fragment length polymorphism in the hemophilia B locus. Hum Genet. 1985;71(1):79–81. doi: 10.1007/BF00295673. [DOI] [PubMed] [Google Scholar]
  5. Chen S. H., Yoshitake S., Chance P. F., Bray G. L., Thompson A. R., Scott C. R., Kurachi K. An intragenic deletion of the factor IX gene in a family with hemophilia B. J Clin Invest. 1985 Dec;76(6):2161–2164. doi: 10.1172/JCI112222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Choo K. H., Gould K. G., Rees D. J., Brownlee G. G. Molecular cloning of the gene for human anti-haemophilic factor IX. Nature. 1982 Sep 9;299(5879):178–180. doi: 10.1038/299178a0. [DOI] [PubMed] [Google Scholar]
  7. Connor J. M., Pettigrew A. F., Hann I. M., Forbes C. D., Lowe G. D., Affara N. A. Application of an intragenic genomic probe to genetic counselling for haemophilia B in the west of Scotland. J Med Genet. 1985 Dec;22(6):441–446. doi: 10.1136/jmg.22.6.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Crum E. D., Shainoff J. R., Graham R. C., Ratnoff O. D. Fibrinogen Cleveland II. An abnormal fibrinogen with defective release of fibrinopeptide A. J Clin Invest. 1974 May;53(5):1308–1319. doi: 10.1172/JCI107678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drayna D., White R. The genetic linkage map of the human X chromosome. Science. 1985 Nov 15;230(4727):753–758. doi: 10.1126/science.4059909. [DOI] [PubMed] [Google Scholar]
  10. Giannelli F., Anson D. S., Choo K. H., Rees D. J., Winship P. R., Ferrari N., Rizza C. R., Brownlee G. G. Characterisation and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency). Lancet. 1984 Feb 4;1(8371):239–241. doi: 10.1016/s0140-6736(84)90122-3. [DOI] [PubMed] [Google Scholar]
  11. Giannelli F., Choo K. H., Rees D. J., Boyd Y., Rizza C. R., Brownlee G. G. Gene deletions in patients with haemophilia B and anti-factor IX antibodies. Nature. 1983 May 12;303(5913):181–182. doi: 10.1038/303181a0. [DOI] [PubMed] [Google Scholar]
  12. Gitschier J., Wood W. I., Tuddenham E. G., Shuman M. A., Goralka T. M., Chen E. Y., Lawn R. M. Detection and sequence of mutations in the factor VIII gene of haemophiliacs. 1985 May 30-Jun 5Nature. 315(6018):427–430. doi: 10.1038/315427a0. [DOI] [PubMed] [Google Scholar]
  13. Graham J. B., Green P. P., McGraw R. A., Davis L. M. Application of molecular genetics to prenatal diagnosis and carrier detection in the hemophilias: some limitations. Blood. 1985 Oct;66(4):759–764. [PubMed] [Google Scholar]
  14. Grunebaum L., Cazenave J. P., Camerino G., Kloepfer C., Mandel J. L., Tolstoshev P., Jaye M., De la Salle H., Lecocq J. P. Carrier detection of Hemophilia B by using a restriction site polymorphism associated with the coagulation Factor IX gene. J Clin Invest. 1984 May;73(5):1491–1495. doi: 10.1172/JCI111354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hassan H. J., Orlando M., Leonardi A., Chelucci C., Guerriero R., Mannucci P. M., Mariani G., Peschle C. Intragenic Factor IX restriction site polymorphism in hemophilia B variants. Blood. 1985 Feb;65(2):441–443. [PubMed] [Google Scholar]
  16. Hay C. W., Robertson K. A., Yong S. L., Thompson A. R., Growe G. H., MacGillivray R. T. Use of a BamHI polymorphism in the factor IX gene for the determination of hemophilia B carrier status. Blood. 1986 May;67(5):1508–1511. [PubMed] [Google Scholar]
  17. Hoar D. I., Haslam D. B., Starozik D. M. Improved direct molecular diagnosis and rapid fetal sexing. Prenat Diagn. 1984 Jul-Aug;4(4):241–247. doi: 10.1002/pd.1970040402. [DOI] [PubMed] [Google Scholar]
  18. Jaye M., de la Salle H., Schamber F., Balland A., Kohli V., Findeli A., Tolstoshev P., Lecocq J. P. Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX. Nucleic Acids Res. 1983 Apr 25;11(8):2325–2335. doi: 10.1093/nar/11.8.2325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Kurachi K., Davie E. W. Isolation and characterization of a cDNA coding for human factor IX. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6461–6464. doi: 10.1073/pnas.79.21.6461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lagrimini L. M., Brentano S. T., Donelson J. E. A DNA sequence analysis package for the IBM personal computer. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):605–614. doi: 10.1093/nar/12.1part2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Laurell C. B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem. 1966 Apr;15(1):45–52. doi: 10.1016/0003-2697(66)90246-6. [DOI] [PubMed] [Google Scholar]
  23. Markova I., Forbes C. D., Inwood M. The consumers' views of genetic counseling of hemophilia. Am J Med Genet. 1984 Apr;17(4):741–752. doi: 10.1002/ajmg.1320170405. [DOI] [PubMed] [Google Scholar]
  24. McGraw R. A., Davis L. M., Noyes C. M., Lundblad R. L., Roberts H. R., Graham J. B., Stafford D. W. Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX. Proc Natl Acad Sci U S A. 1985 May;82(9):2847–2851. doi: 10.1073/pnas.82.9.2847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mulligan L. M., Phillips M. A., Forster-Gibson C. J., Beckett J., Partington M. W., Simpson N. E., Holden J. J., White B. N. Genetic mapping of DNA segments relative to the locus for the fragile-X syndrome at Xq27.3. Am J Hum Genet. 1985 May;37(3):463–472. [PMC free article] [PubMed] [Google Scholar]
  26. Peake I. R., Furlong B. L., Bloom A. L. Carrier detection by direct gene analysis in a family with haemophilia B (factor IX deficiency). Lancet. 1984 Feb 4;1(8371):242–243. doi: 10.1016/s0140-6736(84)90123-5. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Thompson A. R. Structure, function, and molecular defects of factor IX. Blood. 1986 Mar;67(3):565–572. [PubMed] [Google Scholar]
  29. Tønnesen T., Søndergaard F., Güttler F., Oberlé I., Moisan J. P., Mandel J. L., Hauge M., Damsgård E. M. Exclusion of haemophilia B in male fetus by chorionic villus biopsy. Lancet. 1984 Oct 20;2(8408):932–932. doi: 10.1016/s0140-6736(84)90690-1. [DOI] [PubMed] [Google Scholar]
  30. Winship P. R., Anson D. S., Rizza C. R., Brownlee G. G. Carrier detection in haemophilia B using two further intragenic restriction fragment length polymorphisms. Nucleic Acids Res. 1984 Dec 11;12(23):8861–8872. doi: 10.1093/nar/12.23.8861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yoshitake S., Schach B. G., Foster D. C., Davie E. W., Kurachi K. Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry. 1985 Jul 2;24(14):3736–3750. doi: 10.1021/bi00335a049. [DOI] [PubMed] [Google Scholar]

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