Cloning of the Duchenne/Becker Muscular Dystrophy Locus

  • Anthony P. Monaco
  • Louis M. Kunkel
Part of the Advances in Human Genetics book series (AHUG, volume 17)

Abstract

The identification and molecular cloning of the Duchenne muscular dystrophy (DMD) gene represents the first step in the long path toward a basic understanding and potential therapy of this human genetic disorder. One of the most interesting challenges to modern medicine is to understand and alter the course of the many genetic disorders. There are more than 3000 known genetic disease phenotypes, yet the vast majority are poorly understood at the level of the underlying biochemical disturbance. The techniques of molecular biology have changed the way these disorders are analyzed, and presumably the next decade will see an explosion of new understanding in the various ways that genotype affects phenotype. Duchenne muscular dystrophy thus serves as an example of the prospects to come, and this review can serve as a guide toward similar work with other genetic disorders.

Keywords

Codon Recombination Fractionation Proline Neurol 

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References

  1. Aldridge, J., Kunkel, L., Bruns, G., Tantravahi, U., Lalande, M., Brewster, T., and Moreau, E., 1984, A strategy to reveal high frequency RFLPs along the human X chromosome, Am. J. Hum. Genet. 36:546–564.PubMedGoogle Scholar
  2. Appel, S. H., and Roses, A. D., 1983, The muscular dystrophies, in: The Metabolic Basis of Inherited Disease (J. B. Stanbury, ed.), pp. 1470–1495, McGraw-Hill, New York.Google Scholar
  3. Baehner, R. L., Kunkel, L. M., Monaco, A. P., Haines, J. L., Conneally, P. M., Palmer, C., Heerema, N., and Orkin, S. H., 1986, DNA linkage analysis of X-chromosome-linked chronic granulomatous disease, Proc. Natl. Acad. Sci. USA 83:3398–3401.CrossRefGoogle Scholar
  4. Bakker, E., Hofker, M. H., Goor, N., Mandel, J. L., Wrogemann, K., Davies, K. E., Kunkel, L. M., Willard, H. F., Fenton, W. A., Sandkuyl, L., van Ommen G. J. B., and Pearson, P. L., 1985, Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs, Lancet 1:655–658.PubMedCrossRefGoogle Scholar
  5. Bakker, E., Van Broeckhoven, Ch., Bonten, E. J., van de Vooren, M. J., Veenema, Van Hul, W., Van Ommen, G. J. B., Vandenberghe, A., and Pearson, P. L., 1987, Germline mosaicism and Duchenne muscular dystrophy mutations, Nature 329:554–556.PubMedCrossRefGoogle Scholar
  6. Bartley, J. A., Patil, S., Davenport, S., Goldstein, D., and Pickens, J., 1986, Duchenne muscular dystrophy, glycerol kinase deficiency, and adrenal insufficiency associated with an Xp21 interstitial deletion, J. Pediatr. 108:189–192.PubMedCrossRefGoogle Scholar
  7. Bender, W., Arkam, M., Karch, F., Beachy, P. A., Peifer, M., Spierer, P., Lewis, E. B., and Hogness, D. S., 1983, Molecular genetics of the bithorax complex in Drosophila melanogaster, Science 221:23–29.PubMedCrossRefGoogle Scholar
  8. Benton, W. D., and Davis, R. W., 1977, Screening lambda-gt recombinant clones by hybridization to single plaques in situ, Science 196:180–182.PubMedCrossRefGoogle Scholar
  9. Bertelson, C. J., Bartley, J. A., Monaco, A. P., Colletti-Feener, C., Fischbeck, K., and Kunkel, L. M., 1986, Localization of Xp21 meiotic exchange points in DMD families, J. Med. Genet. 23:531–537.PubMedCrossRefGoogle Scholar
  10. Bertelson, C. J., Pogo, A. O., Chauduri, A., Marsh, W. L., Redman, C. M., Baneijee, D., Symmans, W. A., Simon, T., Frey, D., and Kunkel, L. M., 1988, Localization of the McLeod locus (XK) within Xp21 by deletion analysis, Am. J. Hum. Genet. 42:703–711.PubMedGoogle Scholar
  11. Blau, H. M., Webster, C., and Pavlath, G. K., 1983, Defective myoblasts identified in Duchenne muscular dystrophy, Proc. Natl. Acad. Sci. USA 80:4856–4860.PubMedCrossRefGoogle Scholar
  12. Bolivar, F., Rodriguez, R. L., Greene, P. J., Betlach, M. C., Heyneker, H. L., Boyer, H. W., Crosa, H. J., and Falkow, S., 1977, Construction and characteristics of new cloning vehicles. II. A multipurpose cloning system, Gene 2:95–113.PubMedCrossRefGoogle Scholar
  13. Botstein, D., White, R. L., Skolnick, M., and Davis, R. W., 1980, Construction of a genetic linkage map in man using restriction fragment length polymorphisms, Am. J. Hum. Genet. 32:314–331.PubMedGoogle Scholar
  14. Boyd, Y., and Buckle, V. J., 1986, Cytogenetic heterogeneity of translocations associated with Duchenne muscular dystrophy, Clin. Genet. 29:108–115.PubMedCrossRefGoogle Scholar
  15. Boyd, Y., Munro, E., Ray, P., Worton, R., Monaco, A., Kunkel, L. M., and Craig, I., 1987, Molecular heterogeneity of translocations associated with muscular dystrophy, Clin. Genet. 31:265–272.PubMedCrossRefGoogle Scholar
  16. Breitbart, R. E., Nguyen, H. T., Medford, R. M., Destree, A. T., Mahdavi, V., and Nadal-Ginard, B., 1985, Intricate combinatorial patterns of exon splicing generate multiple regulated troponin T isoforms, Cell 41:67–82.PubMedCrossRefGoogle Scholar
  17. Britten, R. J., and Kohne, D. E., 1968, Repeated sequences in DNA, Science 161:529–540.PubMedCrossRefGoogle Scholar
  18. Brooke, M. H., Fenichel, G. M., Griggs, R. C., Mendell, J. R., Moxley, R., Miller, J. P., Province, M. A., and the CIDD Group, 1983, Clinical investigations in Duchenne muscular dystrophy: 2. Determination of the “power” of therapeutic trials based on the natural history, Muscle Nerve 6:91–103.PubMedCrossRefGoogle Scholar
  19. Brown, C. S., Thomas, N. S. T., Sarfarazi, M., Davies, K. E., Kunkel, L., Kingston, H. M., Shaw, D. J., and Harper, P. S., 1985, Genetic linkage relationships of seven DNA probes with Duchenne and Becker muscular dystrophy, Hum. Genet. 71:62–74.PubMedCrossRefGoogle Scholar
  20. Brown, W. R. A., and Bird, A. P., 1986, Long range restriction site mapping of mammalian genomic DNA, Nature 322:477–481.PubMedCrossRefGoogle Scholar
  21. Burghes, A. H. M., Logan, C., Hu, X., Beifall, B., Worton, R. G., and Ray, P. N., 1987, A cDNA clone from the Duchenne/Becker muscular dystrophy gene, Nature 328:434–437.PubMedCrossRefGoogle Scholar
  22. Burmeister, M., and Lehrach, H., 1986, Long-range restriction map around the Duchenne muscular dystrophy gene, Nature 324:582–585.PubMedCrossRefGoogle Scholar
  23. Carle, G. F., Frank, M., and Olson, M. V., 1986, Electrophoretic separations of large DNA molecules by periodic inversion of the electric field, Science 4:65–68.CrossRefGoogle Scholar
  24. Carpenter, S., and Karpati, G., 1979, Duchenne muscular dystrophy. Plasma membrane loss initiates muscle cell necrosis unless it is repaired, Brain 104:147–161.PubMedCrossRefGoogle Scholar
  25. Chamberlain, J. S., Pearlman, J. A., Muzny, D. M., Gibbs, R. A., Ranier, J. E., Reeves, A. A., and Caskey, C. T., 1988, Expression of the murine Duchenne muscular dystrophy gene in muscle and brain, Science 239:1416–1418.PubMedCrossRefGoogle Scholar
  26. Chou, P. Y., and Fasman, G. D., 1974, Prediction of protein conformation, Biochemistry 13:222–245.PubMedCrossRefGoogle Scholar
  27. Cohen, C., and Parry, D. A. D., 1986, a-Helical coiled-coils—A widespread motif in proteins, Trends Biochem. Sci. USA 11:1–4.CrossRefGoogle Scholar
  28. Cullen, M. J., and Fulthorpe, J. J., 1975, Stages in fibre breakdown in Duchenne muscular dystrophy: An electron-microscopic study, J. Neurol. Sci. 24:179–200.PubMedCrossRefGoogle Scholar
  29. Darras, B. T., and Francke, U., 1987, A partial deletion of the muscular dystrophy gene transmitted twice by an unaffected male, Nature 329:556–558.PubMedCrossRefGoogle Scholar
  30. Davidson, M. D., and Critchley, D. R., 1988, a-Actinins and the DMD protein contain spectrin-like repeats, Cell 52:159–160.CrossRefGoogle Scholar
  31. Davies, K. E., Young, B. D., Elles, R. G., Hill, M. E., and Williamson, R., 1981, Cloning of a representative genomic library of the human X chromosome after sorting by flow cytometry, Nature 293:374–376.PubMedCrossRefGoogle Scholar
  32. Davies, K. E., Pearson, P. L., Harper, P. S., Murray, J. M., O’Brien, T., Sarfarazzi, M., and 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.PubMedCrossRefGoogle Scholar
  33. DeMartinville, B., Kunkel, L. M., Bruns, G., Morle, F., Koenig, M., Mandel, J. L., Horwich, A., Latt, S. A., Gusella, J. F., Housman, D., and Francke, U., 1985, Localization of DNA sequences in the region Xp21 of the human X chromosome: Search for molecular markers close to the Duchenne muscular dystrophy locus, Am. J. Hum. Genet. 37:235–249.PubMedGoogle Scholar
  34. Dorkins, H., Junien, C., Mandel, J. L., Wrogemann, K., Moison, J. P., Martinez, M., Old, J. M., Bundey, S., Schwartz, M., Carpenter, N., Hill, D., Lindlof, M., de la Chapelle, A., Pearson, P. L., and Davies, K. E., 1985, Segregation analysis of a marker localised on Xp21.2-Xp21.3 in Duchenne and Becker muscular dystrophy families, Hum. Genet. 71:103–107.PubMedCrossRefGoogle Scholar
  35. Dubowitz, V., 1985, Muscular dystrophies, in: Muscle Biopsy, A Practical Approach, Tindall, London.Google Scholar
  36. Emery, A. E. H., and Holloway, S., 1977, Use of normal daughters’ and sisters’ creatine kinase levels in estimating heterozygosity in Duchenne muscular dystrophy, Hum. Hered. 27:118–126.PubMedCrossRefGoogle Scholar
  37. Fadda, S., Mochi, M., Roncuzzi, L., Sangiori, S., Sbarra, D., Katz, M., and Romeo, G., 1985, Definitive localization of Becker muscular dystrophy in Xp by linkage to a cluster of DNA polymorphisms (DXS43 and DXS9), Hum. Genet. 71:33–36.PubMedCrossRefGoogle Scholar
  38. Fingerman, E., Campisi, J., and Pardee, A. B., 1984, Defective Ca2+ metabolism in Duchenne muscular dystrophy: Effects on cellular and viral growth, Proc. Natl. Acad. Sci. USA 81:7617–7621.PubMedCrossRefGoogle Scholar
  39. Fischbeck, K. H., Ritter, A. W., Tirschwell, D. L., Kunkel, L. M., Bertelson, C. J., Monaco, A. P., Hejtmancik, J. F., Boehm, C., Ionasescu, V., Ionasescu, R., Pericak-Vance, M., Kandt, R., and Roses, A. D., 1986, Recombination with pERT87 (DXS164) in families with X-linked muscular dystrophy, Lancet 2:104.PubMedCrossRefGoogle Scholar
  40. Francke, U., Ochs, H. D., de Martinville, B., Giacalone, J., Lindgren, V., Disteche, C. M., Pagon, R. A., Hofker, M. H., van Ommen, G.-J. B., Pearson, P. L., and Wedgwood, R. J., 1985, Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome, Am. J. Hum. Genet. 37:250–267.PubMedGoogle Scholar
  41. Francke, U., Harper, J. F., Darras, B. T., Cowan, J. M., McCabe, E. R. B., Kohlschutter, A., Seltzer, W. K., Saito, F., Goto, J., Harpey, J. P., and Wise, J. E., 1987, Congenital adrenal hypoplasia, myopathy and glycerol kinase deficiency: Molecular genetic evidence for deletions, Am. J. Hum. Genet. 40:212–227.PubMedGoogle Scholar
  42. Fryns, J. P. Kleczkowska, A., Petit, P., and van den Berghe, H., 1982, Fertility in patients with X-chromosome deletions, Clin. Genet. 22:76–79.PubMedCrossRefGoogle Scholar
  43. Goodfellow, P. N., Davies, K. E., and Ropers, H. H., 1985, Report of the committee on the genetic constitution of the X and Y chromosomes, Cytogenet. Cell Genet. 40:296–352.PubMedCrossRefGoogle Scholar
  44. Greenstein, R. M., Reardon, M. P., Chan, T. S., Middleton, A. B., Mulivor, R. A., Greene, A. E., and Coriell, L. L., 1980, An (X;ll) translocation in a girl with Duchenne muscular dystrophy, Cytogenet. Cell. Genet. 27 27:268.PubMedCrossRefGoogle Scholar
  45. Gubler, U., and Hoffman, B. J., 1983, A very simple and very efficient method for generating cDNA libraries, Gene 25:263–269.PubMedCrossRefGoogle Scholar
  46. Hart, K. A., Hodgson, S., Walker, A., Cole, C. G., Johnson, L., Dubowitz, V., and Bobrow, M., 1987a, DNA deletions in mild and severe Becker muscular dystrophy, Hum. Genet. 75:281–285.PubMedCrossRefGoogle Scholar
  47. Hart, K. A., Monaco, A. P., Kunkel, L. M., and Bobrow, M., 1987a, A small deletion in the Duchenne/Becker muscular dystrophy locus—A functionally important region? Hum. Genet. 77:88–91.PubMedCrossRefGoogle Scholar
  48. Hoffman, E. P., Monaco, A. P., Feener, C. C., and Kunkel, L. M., 1987a, Conservation of the Duchenne muscular dystrophy gene in mice and humans, Science 238:347–350.PubMedCrossRefGoogle Scholar
  49. Hoffman, E. P., Brown, R. H., Jr., and Kunkel, L. M., 1987a, Dystrophin: The protein product of the Duchenne muscular dystrophy locus, Cell 51:919–928.PubMedCrossRefGoogle Scholar
  50. Hoffman, E. P., Knudson, C. M., Campbell, K. P., and Kunkel, L. M., 1987c, Subcellular fractionation of dystrophin to the triads of skeletal muscle, Nature 330:754–758.PubMedCrossRefGoogle Scholar
  51. Hoffman, E. P., Fishbeck, K., Brown, R. H., Johnson, M., Medori, R., Loike, J. D., Harris, J. B., Waterston, R., Brooke, M., Specht, L., Kupsky, W., Chamberlain, J., Caskey, C. T., Shapiro, F., and Kunkel, L. M., 1988, Dystrophin quality and quantity determines the clinical severity of Duchenne/Becker muscular dystrophies, N. Engl. J. Med. (in press).Google Scholar
  52. Hofker, M. H., Wapenaar, M. C., Coor, N., Bakker, E., van Ommen, G. J. B., and Pearson, P. L., 1985, Isolation of probes detecting restriction fragment length polymorphisms from X-chromosome specific libraries: Potential use for diagnosis of Duchenne muscular dystrophy, Hum. Genet. 70:148–156.PubMedCrossRefGoogle Scholar
  53. Hu, D. H., Kimura, S., and Maruyama, K., 1986, Sodium dodecyl sulphate gel electrophoresis studies of connectin-like high molecular weight proteins of various types of vertebrate and invertebrate muscles, J. Biochem. 99:1485–1492.PubMedGoogle Scholar
  54. Huynh, T., Young, R. A., and Davis, R. W., 1985, Constructing and screening cDNA libraries in lambda gtlO and gtll, in: DNA Cloning: A Practical Approach (D. M. Glover, ed.), pp. 49–78, Oxford, England.Google Scholar
  55. Jacobs, P. A., Hunt, P. A., Mayer, M., and Bart, R. D., 1981, Duchenne muscular dystrophy (DMD) in a female with an X/autosome translocation: Further evidence that the DMD locus is in Xp21, Am. J. Hum. Genet. 33:513–518.PubMedGoogle Scholar
  56. Kan, Y. W., and Dosy, A. M., 1978, Polymorphism of DNA sequence adjacent to human B-globin structural gene: Relationship to sickle mutation, Proc. Natl. Acad. Sci. USA 75:5631–5635.PubMedCrossRefGoogle Scholar
  57. Kenwrick, S., Patterson, M., Speer, A., Fischbeck, K., and Davies, K., 1987, Molecular analysis of the Duchenne muscular dystrophy region using pulsed field gel electrophoresis, Cell 48:351–357.PubMedCrossRefGoogle Scholar
  58. Kingston, H. M., Sarfarazi, M., Thomas, N. S. T., and Harper, P. S., 1984, Localization of the Becker muscular dystrophy gene on the short arm of the X chromosome by linkage to cloned DNA sequences, Hum. Genet. 67:6–17.PubMedCrossRefGoogle Scholar
  59. Koenig, M., Hoffman, E. P., Bertelson, C. J., Monaco, A. P., Feener, C., and Kunkel, L. M., 1987, Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals, Cell 50:509–517.PubMedCrossRefGoogle Scholar
  60. Koenig, M., Monaco, A. P., and Kunkle, L. M., 1988, The complete sequence of dystrophin predicts a rod-shaped cytoskeletai protein, Cell 53:219–228.PubMedCrossRefGoogle Scholar
  61. Kohne, D. E., Levin son, S. A., and Byers, M. J., 1977, Room temperature method for increasing the rate of DNA reassociation by many thousandfold: The phenol emulsion reassociation technique, Biochemistry 16:5329–5341.PubMedCrossRefGoogle Scholar
  62. Kunkel, L. M., Tantravahi, U., Eisenhard, M., and Latt, S. A., 1982, Regional localization on the human X of DNA segments cloned from flow-sorted chromosomes, Nucleic Acids Res. 10:1557–1578.PubMedCrossRefGoogle Scholar
  63. Kunkel, L. M., Lalande, M., Monaco, A. P., Flint, A., Middlesworth, W., and Latt, S. A., 1985a, Construction of a human X-chromosome-enriched phage library which facilitates analysis of specific loci, Gene 33:251–258.PubMedCrossRefGoogle Scholar
  64. Kunkel, L. M., Monaco, A. P., Middlesworth, W., Ochs, H. D., and Latt, S. A., 1985b, Specific cloning of DNA fragments absent from the DNA of a male patient with an X chromosome deletion, Proc. Natl. Acad. Sci. USA 82:4778–4782.PubMedCrossRefGoogle Scholar
  65. Kunkel, L. M., and co-authors, 1986, Analysis of deletions in the DNA of patients with Becker and Duchenne muscular dystrophy, Nature 322:73–77.PubMedCrossRefGoogle Scholar
  66. Lamar, E. E., and Palmer, E., 1984, Y-encoded, species-specific DNA in mice: Evidence that the Y-chromosome exists in two polymorphic forms in inbred strains, Cell 37:171–177.PubMedCrossRefGoogle Scholar
  67. Lange, K., Kunkel, L. M., Aldridge, J., and Latt, S. A., 1985, Accurate and super-accurate gene mapping, Am. J. Hum. Genet. 37:853–867.PubMedGoogle Scholar
  68. Locker, R. H., and Wild, D. J. C., 1986, A comparative study of high molecular weight proteins in various types of muscle across the animal kingdom, J. Biochem. 99:1473–1484.PubMedGoogle Scholar
  69. Lu, R. C., and Wong, A., 1985, The amino acid sequence and stability predictions of the hinge region in myosin subfragment 2, J. Biol. Chem. 260:3456–3461.PubMedGoogle Scholar
  70. Maxam, A. M., and Gilbert, W., 1977, A new method for sequencing DNA, Proc. Natl. Acad. Sci. USA 74:560–564.PubMedCrossRefGoogle Scholar
  71. McLachlin, A. D., and Kara, J., 1982, Periodic charge distributions in the myosin rod amino acid sequence match cross-bridge spacings in muscle, Nature 299:226–231.CrossRefGoogle Scholar
  72. Mokri, B., and Engel, A. G., 1975, Duchenne dystrophy: Electron microscopic findings pointing to a basic or early abnormality in the plasma membrane of the muscle fibers, Neurology 25:1111–1120.PubMedGoogle Scholar
  73. Monaco, A. P., and Kunkel, L. M., 1987, A giant locus for the Duchenne and Becker muscular dystrophy gene, Trends Genet. 3:33–37.CrossRefGoogle Scholar
  74. Monaco, A. P., Bertelson, C. J., Middlesworth, W., Colletti, C. A., Aldridge, J., Fischbeck, K. H., Bartlett, R., Pericak-Vance, M. A., Roses, A. D., and Kunkel, L. M., 1985, Detection of deletions spanning the Duchenne muscular dystrophy locus using a tightly linked DNA segment, Nature 316:842–845.PubMedCrossRefGoogle Scholar
  75. Monaco, A. P., Neve, R., Colletti-Feener, C., Bertelson, C. J., Kurnit, D. M., and Kunkel, L. M., 1986, Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene, Nature 323:646–650.PubMedCrossRefGoogle Scholar
  76. Monaco, A. P., Bertelson, C. J., Colletti-Feener, C., and Kunkel, L. M., 1987, Localization and cloning of Xp21 deletion breakpoints involved in muscular dystrophy, Hum. Genet. 75:221–227.PubMedCrossRefGoogle Scholar
  77. Monaco, A. P., Bertelson, C. J., Liechti-Gallati, S., Moser, H., and Kunkel, L. M., 1988, An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus, Genomics 2:90–95.PubMedCrossRefGoogle Scholar
  78. Moser, H., 1984, Duchenne muscular dystrophy: Pathogenetic aspects and genetic prevention, Hum. Genet. 66:17–40.PubMedCrossRefGoogle Scholar
  79. Nudel, U., Robzyk K., and Yaffe, D., 1988, Expression of the putative Duchenne muscular dystrophy gene in differentiated myogenic cell cultures and in the brain, Nature 331:635–638.PubMedCrossRefGoogle Scholar
  80. Orkin, S. H., and Kazazian, H. H., Jr., 1984, Mutation and polymorphism of the human B-globin gene and its surrounding DNA, Annu. Rev. Genet. 18:131–171.PubMedCrossRefGoogle Scholar
  81. Perler, F., Efstratiadis, A., Lomedico, P., Gilbert, W., Kolodner, R., and Dodgson, J., 1980, The evolution of genes: The chicken preproinsulin gene, Cell 20:555–566.PubMedCrossRefGoogle Scholar
  82. Ray, P. N., Belfall, B., Duff, C., Logan, C., Kean, V., Thompson, M. W., Sylvester, J. E., Gorski, J. L., Schmickel, R. D., and Worton, R. G., 1985, Cloning of the breakpoint of an X;21 translocation associated with Duchenne muscular dystrophy, Nature 318:672–675.PubMedCrossRefGoogle Scholar
  83. Rosenfeld, M. G., Mermad, J.-J., Amara, S. G., Swanson, L. W., Sawchenko, P. E., Rivier, J., Vale, W., and Evans, R. M., 1983, Production of a novel neuropeptide encoded by the calcitonin gene via tissue specific RNA processing, Nature 304:129–135.PubMedCrossRefGoogle Scholar
  84. Rowland, L. P., 1980, Biochemistry of muscle membranes in Duchenne muscular dystrophy, Muscle Nerve 3:3–20.PubMedCrossRefGoogle Scholar
  85. Rozen, R., Fox, J., Fenton, W. A., Horwich, A. L., and Rosenberg, L. E., 1985, Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus, Nature 313:815–817.PubMedCrossRefGoogle Scholar
  86. Sanger, F., Nicklen, S., and Coulson, A. R., 1977, DNA sequencing with chain-terminating inhibitors, Proc. Natl. Acad. Sci. USA 74:5463–5467.PubMedCrossRefGoogle Scholar
  87. Schwartz, D. C., and Cantor, C. R., 1984, Separation of yeast chromosome-sized DNAs by pulsed field gel electrophoresis, Cell 37:67–75.PubMedCrossRefGoogle Scholar
  88. Singer, M. F., 1982, SINEs and LINEs: Highly repeated short and long interspersed sequences in mammalian genomes, Cell 28:433–434.PubMedCrossRefGoogle Scholar
  89. Strehler, E. E., Strehler-Page, M.-A., Perriard, J.-C., Periasamy, M., and Nadal-Ginard, B., 1986, Complete nucleotide and encoded amino acid sequence of a mammalian myosin heavy chain gene, J. Mol. Biol. 190:291–317.PubMedCrossRefGoogle Scholar
  90. Sugita, H., Arahata, K., Ishiguro, T., Suhara, Y., Tsukahara, T., Ishura, S., Eguchi, C., Nonaka, I., and Ozawa, E., 1988, Negative immunostaining of Duchenne muscular dystrophy (DMD) and mdx muscle surface membrane with antibody against synthetic peptide fragment predicted from DMD cDNA, Proc. Japan Acad. 64:37–39.CrossRefGoogle Scholar
  91. Thomas, P. S., 1980, Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose, Proc. Natl. Acad. Sci USA 77:5201–5205.PubMedCrossRefGoogle Scholar
  92. van Ommen, G.-J. B., Verkerk, J. M. H., Hofker, M. H., Monaco, A. P., Kunkel, L. M., Ray, P., Worton, R., Wieringa, B., Bakker, B., and Pearson, P. L., 1986, A physical map of 4 million bp around the Duchenne muscular dystrophy gene on the human X chromosome, Cell 47:499–504.PubMedCrossRefGoogle Scholar
  93. Verellen-Dumoulin, Ch., Freund, M., DeMeyer, R., Laterre, Ch., Frederic, J., Thompson, M. W., Markovic, V. C., and Worton, R. G., 1984, Expression of an X-linked muscular dystrophy in a female due to translocation involving Xp21and non-random inactivation of the normal X chromosome, Hum. Genet. 67:115–119.PubMedCrossRefGoogle Scholar
  94. Webster, C., Filippi, B., Rinaldi, A., Mastropaolo, C., Tondi, M., Siniscalco, M., and Blau, H. M., 1986, The myoblast defect identified in Duchenne muscular dystrophy is not a primary expression of the DMD mutation, Hum. Genet. 74:74–80.PubMedCrossRefGoogle Scholar
  95. Wetmur, J. G., and Davidson, N., 1968, Kinetics of renaturation of DNA, J. Mol. Biol. 31:349–370.PubMedCrossRefGoogle Scholar
  96. Wieacker, P., Davies, K. E., Cooke, H. J., Pearson, P. L., Williamson, R., Bhattacharya, S., Zimmer, J., and Ropers, H. H., 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.PubMedGoogle Scholar
  97. Wood, D. S., Sorenson, M. M., Eastwood, A. B., Charash, E., and Reuben, J. P., 1978, Duchenne dystrophy: Abnormal generation of tension and Ca+ + regulation in single skinned fibers, Neurology 28:447–457.PubMedGoogle Scholar
  98. Wood, D. S., Zeviani, M., Prelle, A., Bonilla, E., Salviati, G., Miranda, A. F., dMauro, S., and Rowland, L. P., 1987, Is nebulin the defective gene product in Duchenne muscular dystrophy? N. Engl. J. Med. 316::107–108.PubMedGoogle Scholar
  99. Worton, R. G., Duff, C., Sylvester, J. E., Schmickel, R. D., and Willard, H. F., 1984, Duchenne muscular dystrophy involving translocation of the DMD gene next to ribosomal RNA genes, Science 224:1447–1449.PubMedCrossRefGoogle Scholar
  100. Yang, T. P., Patel, P. I., Chinault, A. C., Stout, J. T., Jackson, L. G., Hildebrand, B. M., and Caskey, C. T., 1984, Molecular evidence for new mutations at the HPRT locus in Lesch-Nyhan patients, Nature 310:412–414.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Anthony P. Monaco
    • 1
    • 2
  • Louis M. Kunkel
    • 1
    • 2
  1. 1.Division of Genetics and Mental Retardation Center Children’s Hospital Department of PediatricsHarvard Medical SchoolBostonUSA
  2. 2.Program in Neuroscience Harvard UniversityCambridgeUSA

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