Summary
The frequency of alleles for intragenic (intron 17 and intron 25) and extragenic (DXS15 and DXS52) F8C RFLPs was investigated in the Algerian population. Altogether 287 X chromosomes (97 males and 95 females) were studied. The allele frequencies found with the two intragenic F8C RFLPs were not substantially different from those reported in a Mediterranean population. At the highly polymorphic extragenic DXS52 locus the distribution in Algeria differed from that found in France. A new allele (14kb), called 1 DZ, was found in 3.1% of the chromosomes. Fifty-one families with hemophilia A were studied with the same probes (374 subjects). Of the females, 94% were informative for at least one intra- or extragenic RFLP. Two recombinations were found between DXS52 and F8C, of which one occurred between the DXS15, DXS52 block and F8C, indicating that the two anonymous loci are on the same side of the F8C gene. Only two obvious gene deletions were observed in 73 unrelated hemophiliacs: one encompassed exons 14–22 (about 4.3 kb of cDNA and 36kb of genomic DNA); the other removed the last exon (exon 26, representing 2 kb of cDNA).
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Antonarakis SE, Waber PG, Kittur SD, Patel AS, Kazazian HH, Mellis MA, Count RB, Stamatoyannopoulos G, Bowie W, Fass ND, Pittman DD, Wozny JM, Toole JJ (1985) Hemophilia A: detection of molecular defects and carriers by DNA analysis. N Engl J Med 313:842–848
Antonarakis SE, Youssoufian H, Kazazian HH (1987) Molecular genetics of hemophilia A in man (factor VIII deficiency). Mol Biol Med 4:81–94
Bonifas JM, Morley BJ, Oakey RE, Kan YW, Epstein EH Jr (1987) Cloning of a cDNA for steroid sulfatase: frequent occurrence of gene deletions in patients with recessive X chromosome-linked ichthyosis. Proc Natl Acad Sci USA 84:9248–9251
Brown WT, Gross A, Chan C, Jenkins EC, Mandel JL, Oberlé I, Arveiler B, Novelli G, Thibodeau S, Hagerman R, Summers K, Turner G, White BN, Mulligan L, Forster-Gibson C, Holden JJA, Zoll B, Krawczak M, Goonewardena KH, Petterson U, Holmgren G, Schwartz C, Howard-Peebles PN, Murphy P, Breg WR, Veenema H, Carpenter NJ (1988) Multilocus analysis of the fragile X syndrome. Hum Genet 78:201–205
Chan V, Chan TK, Liu VWS, Wong ACK (1988) Restriction fragment length polymorphism associated with factor VIII-C gene in China. Hum Genet 79:128–131
Driscoll MC, Miller C, Goldberg JD, Aledort LM, Hoyer LW (1986) Recombination between factor VIII.C gene and ST14 locus. Lancet I:279
Gitschier J, Wood WI, Gorolka TM, Wion KL, Chen EY, Eaton DH, Vehar GA, Capon DJ, Lawn RM (1984) Characterization of human factor VIII gene. Nature 312:326–330
Gitschier J, Drayna D, Tuddenham EGD, White RL, Lawn RM (1985) Genetic mapping and diagnosis of hemophilia A achieved through a BclI polymorphism in the factor VIII gene. Nature 314:738–740
Harper K, Winter RM, Pembrey ME, Hartley D, Davies KE, Tuddenham EGD (1984) A clinically useful DNA probe closely linked to haemophilia A. Lancet II:6–8
Janco RL, Phillips JA, Davies KE, Old J, Antonarakis SE (1986) Carrier testing strategy in hemophilia. Lancet I:148–149
Kasper CK, Aldort LM, Aronson D, Edson JR, Fratantoni J, Green D, Hampton JW, Hilgartner MW, Levine PH, MacMillan CW, Pool JG, Shapiro SS, Shulman NR, Van Eyes J (1975) A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 34:869–872
Lathrop M, Lalouel JM, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 81:3443–3446
Lehesjoki AE, Chapelle A de la, Rasi V (1986) Haemophilia A: two recombinations detected with probe St14. Lancet I:280
Mandel JL, Arveiler B, Camerino G, Hanauer A, Heilig R, Koenig M, Oberlé I (1986) Genetic mapping of the human X chromosome: linkage analysis of the q26–q28 region that includes the fragile X locus and isolation of expressed sequences. Cold Spring Harbor Symp Quant Biol 51:195–203
Maniatis T, Fritsch EF, Sambrook J (eds) (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Nafa K, Reghis A, Benabadji M, Delpech M, Kaplan JC (1989) A new TaqI allele at DXS52 frequent in Algeria. Nucleic Acids Res 17:1276
Oberlé I, Camerino G, Heilig R, Grunebaum L, Cazenave J-P, Crapanzano C, Mannuci PM, Mandel JL (1985) Genetic screening for hemophilia A (classic hemophilia) with a polymorphic DNA probe. N Engl J Med 312:682–686
Oberlé I, Camerino G, Wrogemann K, Arveilier B, Hanuer A, Raimondi E, Mandel JL (1987) Multipoint genetic mapping of the Xq26–q28 region in families with fragile X mental retardation and in normal families reveals tight linkage of markers in q26–q28. Hum Genet 77:60–65
Schwartz C (1987) New TaqI alleles at the DXS52 (St14) locus in the Black population (abstract). (9th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 46:689
Wainscoat JS, Kulozik AE, Ramsay M, Falusi AG, Weatherall DJ (1986) A TaqI γ-globin DNA polymorphism: an African-specific marker. Hum Genet 74:90–92
Worton RG, Thompson MW (1988) Genetics of Duchenne muscular dystrophy. Annu Rev Genet 22:601–629
Youssoufian H, Kazazian HH, Phillips DG, Aroni S, Tsiftif G, Brown V, Antonarakis SE (1986) Recurrent mutations in hemophilia A give evidence for CpG mutation hotspots. Nature 324:380–382
Youssoufian H, Antonarakis SE, Bell W, Griffin AM, Kazazian HH (1988) Nonsense and missense mutations in hemophilia A: estimation of the relative mutation rate at CG dinucleotides. Am J Hum Genet 42:718–725
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Nafa, K., Meriane, F., Reghis, A. et al. Investigation of factor VIII:C gene restriction fragment length polymorphisms and search for deletions in hemophiliac subjects in Algeria. Hum Genet 84, 401–405 (1990). https://doi.org/10.1007/BF00195808
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DOI: https://doi.org/10.1007/BF00195808