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Regional localization of the TIMP gene on the human X chromosome

Extension of a conserved synteny and linkage group on proximal Xp

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Summary

The gene encoding a tissue inhibitor of metalloproteinases, TIMP, has previously been shown to be X-linked in both the human and mouse genomes. We have used a series of somatic cell hybrids segregating translocation and deletion X chromosomes to map the TIMP gene on the human X chromosome. In combination with previous data, the gene can be assigned to Xp11.23→Xp11.4. Genetic linkage analyses demonstrate that TIMP is linked to the more distal ornithine transcarbamylase (OTC) locus at a distance of about 22 centimorgans. The data are consistent with the conclusion that TIMP maps to a conserved synteny and linkage group on the proximal short arm of the human X chromosome and on the pericentric region of the mouse X chromosome, including loci for synapsin-1, a member of the raf oncogene family, OTC, and TIMP.

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References

  • Amar LC, Dandolo L, Hanauer A, Cook AR, Arnaud D, Mandel JL, Avner P (1988) Conservation and reorganization of loci on the mammalian X chromosome: a molecular framework for the identification of homologous subchromosomal regions in man and mouse. Genomics 2:220–230

    Google Scholar 

  • Brown CJ, Willard HF (1987) MspI RFLP detected with chromosome-walk clone pXUT23-SE3.2L from DXS16 in Xp22.1-22.3. Nucleic Acids Res 15:9614

    Google Scholar 

  • Byers PH, Siegal RC, Holbrook KA, Narayanan AS, Bornstein P, Hall JG (1980) X-linked cutis laxa: defective collagen crosslink formation due to decreased lysyl oxidase activity. N Engl J Med 303:61–65

    Google Scholar 

  • Danks DM (1983) Hereditary disorders of copper metabolism in Wilsons disease and Menkes disease. 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 1251–1268

    Google Scholar 

  • Davies KE, Speer A, Herrmann F, Spiegler AWJ, McGlade S, Hofker MH, Briand P, Hanke R, Schwartz M, Steinbicker V, Szibor R, Korner H, Sommer D, Pearson PL, Coutelle C (1985) Human X chromosome markers and Duchenne muscular dystrophy. Nucleic Acids Res 13:3419–3426

    Google Scholar 

  • Davies KE, Mandel JL, Weissenbach J, Fellous M (1987) Report of the committee on the genetic constitution of the X and Y chromosomes. Cytogenet Cell Genet 46:277–315

    Google Scholar 

  • Davisson MT (1987) X-linked genetic homologies between mouse and man. Genomics 1:213–227

    Google Scholar 

  • DiFerrante NM, Leachman RD, Angelini P, Donnelly PV, Francis G, Almazan A (1975) Lysyl oxidase activity deficiency in Ehlers-Danlos syndrome type V. Connect Tissue Res 3:49–53

    Google Scholar 

  • Docherty AJP, Lyons A, Smith BJ, Wright EM, Stephens PE, Harris TJR, Murphy G, Reynolds JJ (1985) Sequence of human tissue inhibitor of metalloproteinases and its identity to erythroid potentiating activity. Nature 318:66–69

    Google Scholar 

  • Dorkins H, Junien C, Mandel JL, Wrogemann K, Moisan JP, Martinez M, Old JM, Bundey S, Schwartz M, Carpenter N, Hill D, Lindlof M, Chapelle A de la, Pearson PL, Davies KE (1985) Segregation analysis of a marker located in Xp21.2–Xp21.3 in Duchenne and Becker muscular dystrophy families. Hum Genet 71:103–107

    Google Scholar 

  • Drayna D, White RL (1985) The genetic linkage map of the human X chromosome. Science 230:753–758

    Google Scholar 

  • Durfy SJ, Clark SC, Williams BRG, Willard HF (1986) RFLP detected by an X-linked cDNA encoding EPA/TIMP. Nucleic Acids Res 14:9226

    Google Scholar 

  • Edwards D, Murphy G, Reynolds J, Whitham S, Docherty A, Angel P, Henth J (1987) Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J 6:1899–1904

    Google Scholar 

  • Francke U, Taggert RT (1980) Comparative gene mapping: order of loci on the X chromosome is different in mice and humans. Proc Natl Acad Sci USA 77:3595–3599

    Google Scholar 

  • Gasson JC, Gold DW, Kaufman SE, Westbrook CA, Hewick RM, Kaufman RJ, Wong GC, Temple PA, Brown EL, Orr EC, Clark SC (1985) Molecular characterization and expression of the gene encoding erythoid-potentiating activity. Nature 315:768–771

    Google Scholar 

  • Goodfellow PN, Davies KE, Ropers HH (1985) Report of the committee on the genetic constitution of the X and Y chromosomes. Cytogenet Cell Genet 40:296–352

    Google Scholar 

  • Horn N, Stene J, Mollekaer AM, Friedrich U (1984) Linkage studies in Menkes disease: the Xg blood group system and C-banding of the X chromosome. Ann Hum Genet 48:161–172

    Google Scholar 

  • Huebner K, Isobe M, Gasson JC, Golde DW, Croce CM (1986a) Localization of the gene encoding erythroid-potentiating activity to chromosome region Xp11.1–Xp11.4. Am J Hum Genet 38:819–826

    Google Scholar 

  • Huebner K, ArRushdi A, Griffin CA, Isobe M, Kozak C, Emanuel BS, Nagarajan L, Cleveland JL, Bonner TI, Goldsborough MD, Croce CM, Rapp U (1986b) Actively transcribed gene in the raf oncogene group located on the X chromosome in mouse and human. Proc Natl Acad Sci USA 83:3934–3938

    Google Scholar 

  • Ingle C, Williamson R, Chapelle A de la, Herva RR, Haapala K, Bates G, Willard HF, Pearson PL, Davies KE (1985) Mapping DNA sequences in a human X chromosome deletion which extends across the region of the Duchenne muscular dystrophy mutation. Am J Hum Genet 37:451–462

    Google Scholar 

  • Jackson IJ, LeCras TD, Docherty AJP (1987) Assignment of the TIMP gene to the murine X chromosome using an interspecies cross. Nucleic Acids Res 15:4357

    Google Scholar 

  • Kapur S, Higgins JV, Delp K, Rogers B (1987) Menkes syndrome in a girl with X-autosome translocation. Am J Med Genet 26:503–510

    Google Scholar 

  • Lindgren V, Martinville B de, Horwich AL, Rosenberg LE, Francke U (1984) Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus. Science 226:698–700

    Google Scholar 

  • Lyon M (1988) X chromosome inactivation and the location and expression of X-linked genes. Am J Hum Genet 42:8–16

    Google Scholar 

  • Mahtani MM, Willard HF (1988) A primary genetic linkage map of the pericentromeric region of the human X chromosome. Genomics 2:294–301

    Google Scholar 

  • Martinville B de, Kunkel LM, Bruns G, Morle F, Koenig M, Mandel JL, Horwich A, Latt SA, Gusella JF, Housman D, Francke U (1985) Localization of DNA sequences in 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

    Google Scholar 

  • McKusick VA (1986) Mendelian inheritance in man, 7th edn. Johns Hopkins University Press, Baltimore

    Google Scholar 

  • Mullins LJ, Grant SG, Stephenson DA, Chapman VM (1988) Multilocus molecular mapping of the mouse X chromosome. Genomics 3:187–194

    Google Scholar 

  • Myerowitz R, Piekarz R, Neufeld EF, Shows TB, Suzuki S (1985) Human beta hexosaminidase alpha chain: coding sequence and homology with the beta chain. Proc Natl Acad Sci USA 82:7830–7834

    Google Scholar 

  • Peltonen L, Kuivaniemi H, Palotie A, Horn N, Kaitila I, Kivirikko KI (1983) Alterations in copper and collagen metabolism in the Menkes syndrome and in a new subtype of the Ehlers-Danlos syndrome. Biochemistry 22:6156–6163

    Google Scholar 

  • Rowe DW, McGoodwin EB, Martin GR, Sussman MD, Grahn D, Faris B, Franzblau C (1974) A sex-linked defect in the cross-linking of collagen and elastin associated with the mottled locus in mice. J Exp Med 139:180–192

    Google Scholar 

  • Spurr NK, Goodfellow PN, Docherty AJP (1987) Chromosomal assignment of the gene encoding the human tissue inhibitor of metalloproteinases to Xp11.1–Xp11.4. Ann Hum Genet 51:189–194

    Google Scholar 

  • Tuinen P van, Rich DC, Summers KM, Ledbetter DH (1987) Regional mapping panel for human chromosome 17: application to neurofibromatosis type I. Genomics 1:374–381

    Google Scholar 

  • Waye JS, England SB, Willard HF (1987) Genomic organization of alpha satellite DNA on human chromosome 7: evidence for two distinct alphoid domains on a single chromosome. Mol Cell Biol 7:349–356

    Google Scholar 

  • Wienker TF, Wieacker P, Cooke HJ, Horn N, Ropers HH (1983) Evidence that the Menkes locus maps on proximal Xp. Hum Genet 65:72–73

    Google Scholar 

  • Willard HF, Riordan JR (1985) Assignment of the gene for myelin proteolipid protein to the X chromosome: implications for X-linked myelin disorders. Science 230:940–942

    Google Scholar 

  • Worton RG, Duff C, Sylvester JE, Schmickel RD, Willard HF (1984) Duchenne muscular dystrophy involving translocation of the dmd gene next to ribosomal RNA genes. Science 224:1447–1449

    Google Scholar 

  • Yang-Feng TL, DeGennaro LJ, Francke U (1986) Genes for synapsin I, a neuronal phosphoprotein, map to conserved regions of human and murine X chromosomes. Proc Natl Acad Sci USA 83:8679–8683

    Google Scholar 

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Authors and Affiliations

  1. Department of Medical Genetics, University of Toronto, Medical Sciences Building 4282, M5S 1A8, Ontario, Toronto, Canada

    H. F. Willard, S. J. Durfy, M. M. Mahtani & B. R. G. Williams

  2. Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, OX3 9DU, Oxford, UK

    H. Dorkins & K. E. Davies

  3. Research Institute, Hospital for Sick Children, M5G 1X8, Toronto, Ontario, Canada

    B. R. G. Williams

Authors
  1. H. F. Willard
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  2. S. J. Durfy
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  3. M. M. Mahtani
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  4. H. Dorkins
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  5. K. E. Davies
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  6. B. R. G. Williams
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Willard, H.F., Durfy, S.J., Mahtani, M.M. et al. Regional localization of the TIMP gene on the human X chromosome. Hum Genet 81, 234–238 (1989). https://doi.org/10.1007/BF00278995

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  • DOI: https://doi.org/10.1007/BF00278995

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