Summary
We have isolated a DNA segment, pX58dIIIc, from an X-chromosome library which identifies an SstI restriction fragment length polymorphism (RFLP) at locus DXS99. Linkage analysis in six informative families has shown that the DXS99 locus lies close to the factor IX gene (F9). No recombination was detected between these loci in 39 informative meioses (Z=9.79, θ=0.0). Therefore, DXS99 will be useful as a DNA marker for the assessment of carrier status in families with haemophilia B where intragenic markers are not informative. Heterozygosity at DXS99 is approximately 50% and, in conjunction with the RFLPs at F9, 90% of females at risk for being haemophilia B carriers should be diagnosed.
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Anson DS, Choo KH, Rees DJG, Giannelli F, Gould K, Huddleston JA, Brownlee GG (1984) The gene structure of antihaemophilic factor IX. EMBO J 3:1053–1060
Beckett LJ, Holden JJA, Simpson NE, White BN, MacLeod PM (1986) Localization of X-linked dominant Charcot-Marie-Tooth disease (CMT 2 to Xq13). J Neurogenet 3:255–231
Camerino G, Grzeschik KH, Jaye M, De La, Salle H, Tolstoshev P, Lecocq JP, Heilig R, Mandel JL (1984) Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (haemophilia B locus). Proc Natl Acad Sci USA 81:498–502
Camerino G, Oberle I, Drayna D, Mandel JL (1985) A new MspI restriction fragment length polymorphism in the hemophilia B locus. Hum Genet 71:79–81
Drayna D, White R (1985) The genetic linkage map of the human X chromosome. Science 230:753–758
Drayna D, Davies K, Hartley O, Mandel J-L, Camarino G, Williamson R (1983) Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms. Proc Natl Acad Sci USA 81:2836–2839
Forster-Gibson CJ, Mulligan LM, Partington MW, Simpson NE, Holden JJA, White BN (1985) The genetic distance between the coagulation factor IX gene and the locus for the fragile X syndrome: clinical implications. J Neurogenet 2:231–237
Forster-Gibson CJ, Mulligan LM, Simpson NE, White BN, Holden JJA (1986) As assessment of the use of flanking DNA markers for Fra(X) syndrome carrier detection and prenatal diagnosis. Am J Med Genet 23:665–683
Giannelli F, Choo KH, Rees DJG, Boyd Y, Rizza CR, Brownlee GG (1983) Gene deletions in patients with haemophilia B anti-factor IX antibodies. Nature 303:181–182
Goodfellow PJ, White BN, Holden JJA, Duncan AMV, Sears EVP, Wang HS, Berlin L, Kidd KK, Simpson NE (1985) Linkage analysis of a DNA marker localized to 20p12 and multiple endocrine neoplasia type 2A. Am J Hum Genet 37:890–897
Gusella JF, Wexler NS, Conneally PM, et al. (1983) A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306:234–238
Hay CW, Robertson KA, Yong SN, Thompson AR, Growe GH, MacGillivray RCA (1986) Use of Bam HI polymorphism in the factor IX gene for the determination, of hemophilia B carrier status. Blood 67:1508–1511
McKee PA (1983) Hemostasis and disorders of blood coagulation. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 1531–1560
Mulligan LM, Phillips MA, Forster-Gibson CJ, Beckett J, Partington MW, Simpson NE, Holden JJA, White BN (1985) Genetic mapping of DNA segments relative to the locus for the fragile-X syndrome at Xq27.3. Am J Hum Genet 37:463–472
Oberle I, Camerino G, Heilig R, Grenebaum L, Casenave JP, Cropanzano C, Mannucci PM, Mandel JL (1985) Genetic screening for haemophilia A (classic haemophilia) with a polymorphic DNA probe. N Engl J Med 312:682–686
Ott J (1976) A computer program for linkage analysis of general human pedigrees. Am J Hum Genet 28:528–529
Peake IR, Bloom AL (1986) Recombination between genes and closely linked polymorphisms. Lancet I:1335
Riddell DC, Wang HS, Beckett J, Chan A, Holden JJA, Mulligan LM, Phillips MA, Simpson NE, Wrogemann K, Hamerton JL, White BN (1986) Regional localization of 18 human X-linked DNA sequences. Cytogenet Cell Genet 42:123–128
Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517
Winship PR, Brownlee GG (1986) Diagnosis of hemophilia B carriers using intragenic oligonucleotide probes. Lancet II:218–219
Winship PR, Anson DS, Riza CR, Brownlee GG (1984) Carrier detection in haemophilia B using two further intragenic restriction fragment length polymorphisms. Nucleic Acids Res 12:8861–8872
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Mulligan, L., Holden, J.J.A. & White, B.N. A DNA marker closely linked to the factor IX (haemophilia B) gene. Hum Genet 75, 381–383 (1987). https://doi.org/10.1007/BF00284113
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DOI: https://doi.org/10.1007/BF00284113