Summary
We have characterized 19 DNA fragments originating from the human X chromosome. Most of them have been isolated from an X chromosome genomic library (Davies et al. 1981) using a systematic screening procedure. These DNA probes have been used to search for restriction fragment length polymorphisms (RFLP). The frequency of restriction polymorphisms (1 per 350 bp analysed) was lower than expected from data obtained with autosomal fragments. The various probes have been mapped within 12 subchromosomal regions using a panel of human-rodent hybrid cell lines. The validity of the panel was established by hybridization experiments performed with 27 X-specific DNA probes, which yielded information on the relative position of translocation break-points on the X chromosome. The DNAs from the various hybrid lines are blotted onto a reusable support which allows one to quickly map any new X-specific DNA fragment. The probes already isolated should be of use to map unbalanced X chromosome aberrations or to characterize new somatic cell hybrid lines. The probes which detect RFLPs define new genetic markers which will help to construct a detailed linkage map of the human X chromosome, and might also serve for the diagnosis of carriers or prenatal diagnosis.
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Aldridge J, Kunkel L, Bruns G, Tantravahi U, Lalande M, Brewster T Moreau E, Wilson M, Bromley W, Roderick T, Latt SA (1984) A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet 36:546–564
Alwine JC, Kemp DJ, Parker BA, Reiser J, Renart J, Stark GR, Wahl GM (1979) Detection of specific RNAs or specific fragments of DNA by fractionation in gels and trasnfer to diazobenzyloxymethyl paper. Methods Enzymol 68:220–242
Bakker E, Goor N, Wrogemann K, Kunkel LM, Fenton WA, Majoor-Krakauer D, Jahoda MGJ, Van Ommen GJB, Hofker MH, Mandel JL, Davies KE, Willard HF, Sandkuyl L, Essen AJV, Sachs ES, Pearson PL (1985) Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs. Lancet I:655–658
Balazs I, Purrello M, Kurnit DM, Grzeschick KH, Siniscalco M (1984) Isolation and characterization of human random cDNA clones homologous to DNA from the X-chromosome. Somatic Cell Mol Genet 10:385–397
Barker D, Schafer M, White R (1984) Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell 36:131–138
Bellard M, Kuo MT, Dretzen G, Chambon P (1980) Differential nuclease sensitivity of the ovalbumin and β-globin chromatin regions in erythrocytes and oviduct cells of laying hen. Nucleic Acids Res 8:2737–2750
Bishop CE, Guellaen G, Geldwerth D, Fellous M, Weissenbach J (1984) Extensive sequence homologies between Y and other human chromosomes. J Mol Biol 173:403–417
Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment lenght polymorphisms. Am J Hum Genet 32:314–331
Boué J, Oberlé I, Mandel JL, Moser A, Moser H, Larsen JW, Dumez Y, Boué A (1985) First trimester prenatal diagnosis of adrenoleukodystrophy by determination of very long chain fatty acid levels and by linkage analysis to a DNA probe. Hum Genet 69: 272–274
Boyd Y, Buckle VJ, Munro EA, Choo KH, Migeon BR, Craig WI (1984) Assignment of the hemophilia B (factor IX) locus to the q26-qter region of the X chromosome. Ann Hum Genet 48:145–152
Camerino G, Mattei MG, Mattei JF, Jaye M, Mandel JL (1983) Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male. Nature 306:701–704
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 (hemophilia B locus). Proc Natl Acad Sci USA 81:498–502
Camerino G, Oberlé I, Drayna D, Mandel JL (1985) A new MspI restriction fragment length polymorphism in the hemophilia B locus. Hum Genet 71:79–81
Chance PF, Dyer KA, Kurachi K, Yoshitake S, Ropers HH, Wieacker P, Gartler SM (1983) Regional localization of the human factor IX gene by molecular hybridization. Hum Genet 65:207–208
Cooper DN, Schmidtke, J (1984) DNA restriction fragment length polymorphisms and heterozygosity in the human genome. Hum Genet 66:1–16
Cooper DN, Smith BA, Cooke HJ, Niemann S, Schmidtke J (1985) An estimate of unique DNA sequence heterozygosity in the human genome. Hum Genet 69:201–205
Davies KE, Young BD, Elles RG, Hill ME, Williamson R (1981) Cloning of a representative genomic library of the human X chromosome after sorting by flow cytometry. Nature 293:374–376
Davies KE, Pearson PL, Harper PS, Murray JM, O'Brien T, Sarfarazi M, Williamson R (1983) Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome. Nucleic Acids Res 11:2303–2312
de Martinville D, Kunkel LM, Bruns G, Koenig M, Morlé F, Mandel JL, Horwich A, Latt SA, Gusella GF, Housman D, Francke U (1985) Localization of DNA sequences in region Xp21 of the human X chromsome: search for molecular markers close to the Duchenne muscular dystrophy locus. Am J Hum Genet 37:235–249
Di Cioccio RA, Voss R, Krim M, Grzeschik KH, Siniscalco M (1975) Identification of human RNA transcripts among heterogeneous nuclear RNA from man-mouse somatic cell hybrids. Proc Natl Acad Sci USA 72:1868–1872
Drayna D, Davies K, Hartley D, Mandel JL, Camerino G, Williamson R, White R (1984) Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms. Proc Natl Acad Sci USA 81:2836–2839
Geldwerth D, Bishop C, Guellaen G, Koenig M, Vergnaud G, Mandel JL, Weissenbach J (1985) Extensive DNA sequence homologies between the human Y and the long arm of the X chromosome. EMBO J 14:1739–1743
Gruncbaum L, Cazenave JP, Camerino G, Kloepfer C, Mandel JL, Tolstoshev P, Jaye M, De la Salle H, Lecocq JP (1984) Carrier detection of hemophilia B by using a restriction site polymorphism associated with the coagulation factor IX gene. J Clin Invest 73: 1491–1495
Grzeschik KH (1976) Assignment of a structural gene for β-glucuronidase to human chromosome C7. Somatic Cell Genet 2: 401–410
Grzeschik KH, Siniscalco M (1976) Identification of a de novo chromosome rearrangement in a man-mouse hybrid clone and its bearing on the cytological map of the human X, chromosome. Cytogenet Cell Genet 16:149–156
Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY, Young AB, Shoulson I, Bonilla E, Martin JB (1983) A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306:234–238
Hanauer A, Mandel JL (1984) The glyceraldehyde-3-phosphate dehydrogenase gene family: structure of a human cDNA and of an X chromosome linked pseudogene; amazing complexity of the gene family in mouse. EMBO J 3:2627–2633
Hanauer A, Levin M, Heilig R, Daegelen D, Kahn A, Mandel JL (1983) Isolation and characterization of cDNA clones for human skeletal muscle α actin. Nucleic Acids Res 11:3503–3516
Heilig R, Hanauer A, Grzeschik KH, Hors-Cayla MC, Mandel JL (1984) Actin-like sequences are present on human X and Y chromosome. EMBO J 3:1803–1807
Hellkuhl B, Mayr WR, Grzeschik KH (1978) Localization of MPI, PKM2, IDHM and the α subunit of hexosaminidases (HEXA) to the q21→qter region of human chromosome 15. Cytogenet Cell Genet 22:503–505
Hellkuhl B, De la Chapelle A, Grzeschik KH (1982) Different patterns of X chromosome inactivity in lymphocytes and fibroblasts of a human balanced X: autosome translocation. Hum Genet 60:126–129
Hors-Cayla MC, Junien C, Heuertz S, Mattei JF, Frézal J (1981) Regional assignment of ARSA, mitochondrial aconitase, and NADH-cytochrome b5 reductase by somatic cell hybridization. Hum Genet 58:140–143
Ish-Horowicz D, Burke JF (1981) Rapid and efficient cosmid cloning. Nucleic Acids Res 9:2989–2998
Jeffreys AJ (1979) DNA sequence variants in the Gγ-, Aγ, δ, and β-globin genes of man. Cell 18:1–10
Koenig M, Camerino G, Heilig R, Mandel JL (1984) A DNA fragment from the human X chromosome short arm which detects a partially homologous sequence on the Y chromosomes long arm. Nucleic Acids Res 12:4097–4019
Koenig M, Moisan JP, Heilig R, Mandel JL (1985) Homologies between X and Y chromosomes detected by ADN probes: localisation and evolution. Nucleic Acids Res 13:5485–5501
Laisney V, Van Cong N, Gross MS, Parisi I, Foubert C, Weil D, Frézal J (1983) Localisation du groupe synténique LDHA-GST3-ESA4 sur le chromosome 11 chez l'homme. Ann Genet (Paris) 26:69–74
Mandel JL, Chambon P (1979) DNA methylation: organ-specific variations in the methylation pattern within and around ovalbumin and other chicken genes. Nucleic Acids Res 7:2081–2103
Mattei MG, Beateman MA, Heilig R, Oberlé I, Davies K, Mandel JL, Mattei JF (1985) Three probe localizations by in situ hybridization with respect to the fragile X breakpoint. Hum Genet 69: 327–331
Murray JG, Demopulos CM, Lawn RM, Motulsky AG (1983) Molecular genetics of human serum albumin: restriction enzyme fragment length polymorphisms and analbuminemia. Proc Natl Acad Sci USA 80:5951–5955
Oberlé I, Camerino G, Heilig R, Grunebaum L, Cazenave JP, Crapanzano C, Manucci PM, Mandel JL (1985a) Genetic screening for hemophilia A (classic hemophilia) with a polymorphic DNA probe. N Engl J Med 312:682–686
Oberlé I, Drayna D, Camerino G, White R, Mandel JL (1985b) The telomeric region of the human X chromosome long arm: presence of a highly polymorphic DNA marker and analysis of recombination frequency. Proc Natl Acad Sci USA 82:2824–2828
Oberlé I, Heilig R, Moisan JP, Kloepfer C, Mattéi MG, Mattéi JF, Boué J, Froster-Iskenius U, Jacobs PA, Lathrop GM, Lalouel JM, Mandel JL (1986) Genetic analysis of the fragile-X mental retardation syndrome with two flanking polymorphic DNA markers. Proc Natl Acad Sci USA 82 (in press)
Purrello M, Alhadeff B, Esposito D, Szabo P, Rocchi M, Truett M, Masiarz F, Siniscalco M (1985) The human genes for hemophilia A and B flank the X-chromosome fragile site at Xq27.3. EMBO J 4:725–729
Ruddle FH (1981) A new era in mammalian gene mapping: somatic cell genetics and recombinant DNA methodologies. Nature 294: 115–120
Savatier P, Trabuchet G, Faure C, Chebloune Y, Gouy M, Verdier G, Nigon VM (1985) Evolution of the primate β-globin gene region. High rate of variation in CpG dinucleotides and in short repeated sequences between man and chimpanzee. J Mol Biol 182:21–29
Seravalli E, DeBona P, Velivasakis M, Pagan-Charry I, Hershberg A, Siniscalco M (1976) Further data on the cytologic mapping of the human X chromosome with man-mouse cell hybrids. Cytogenet Cell Genet 16:219–222
Skolnick MH, Willard HF, Menlove LA (1984) Report of the committee on human gene maping by recombinant DNA techniques. Cytogenet Cell Genet 37:210–273
Turleau C, Chavin-Colin F, DeGrouchy S, Repessé G, Beauvais P (1977) Familial t(X;2)(p223;q323) with partial trisomy 2q and male and female balanced carriers. Hum Genet 37:97–104
Weil D, Van-Cong N, Rebourcet R, Frézal J (1978) Localisation régionale des gènes humains LDHB, TPI, ENO2, PepB, PGK, αGalA, G6PD, HGPRT par l'hybridation cellulaire interspécifique. Hum Genet 42:181–188
Weil D, Van-Cong N, Rebourcet R, Gross MS, Foubert C, Frézal J (1981) Regional localization of the genes for human HEXB, PGK, GALA, HPRT, G6PD by somatic cell hybridization. Ann Genet (Paris) 24:89–92
Wieacker P, Davies KE, Cooke HJ, Pearson PL, Williamson R, Bhattacharya S, Zimmer J, Ropers HH (1984) Toward a complete linkage map of the human X chromosome: regional assignment of 16 cloned single-copy DNA sequences employing a panel of somatic cell hybrids. Am J Hum Genet 36:265–276
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Oberlé, I., Camerino, G., Kloepfer, C. et al. Characterization of a set of X-linked sequences and of a panel of somatic cell hybrids useful for the regional mapping of the human X chromosome. Hum Genet 72, 43–49 (1986). https://doi.org/10.1007/BF00278816
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DOI: https://doi.org/10.1007/BF00278816