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Use of Metaphase-Chromosome Transfer for Mammalian Gene Mapping

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Gene Transfer

Abstract

The mapping of mammalian chromosomes can be approached by two basic strategies: genetic linkage and physical mapping. The precision with which genetic mapping can be applied to a given chromosomal region is directly related to the number of polymorphic markers available in that region and the spacing of those markers within the region. Physical mapping techniques are limited by the sizes of DNA fragments that can be manipulated, and until recently, these limits were in the range of tens of kilobase pairs of DNA. Recent technical innovations promise the potential for manipulating mammalian DNA segments hundreds of kilobase pairs in length. It is clear that the power of both genetic-linkage and physical-isolation techniques would be enhanced by the ability to isolate and characterize chromosomal segments 105 base pairs or greater in length by a direct genetic technique. Previously, we have suggested a strategy based on metaphase-chromosome transfer to address this issue (Housman et al., 1983). For the past several years, our research efforts have been devoted to development of this strategy. The results presented herein bear on the utility of chromosome transfer both for the physical mapping of chromosomes and for the development of DNA-based markers at intervals of a centimorgan or less within these chromosomal segments.

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References

  • Burch, J. W., and McBride, O. W., 1975, Human gene expression in rodent cells after uptake of isolated metaphase chromosomes, Proc. Natl. Acad. Sci. U.S.A. 72: 1797–1801.

    Article  PubMed  CAS  Google Scholar 

  • Capecchi, M. R., 1980, High efficiency transformation by direct microinjection of DNA into cultured mammalian cells, Cell 22: 479–488.

    Article  PubMed  CAS  Google Scholar 

  • Cepko, C. L., Roberts, B. E., and Mulligan, R. C., 1984, Construction and applications of a highly transmissible murine retrovirus shuttle vector, Cell 37: 1053–1062.

    Article  PubMed  CAS  Google Scholar 

  • Chao, M. V., Mellon, P., Charnay, P., Maniatis, T., and Axel, R., 1983, The regulated expression of beta globin genes introduced into mouse erythroleukemia cells, Cell 32: 483–493.

    Article  PubMed  CAS  Google Scholar 

  • Cirullo, R. E., Dana, S., and Wasmuth, J. J., 1983, Efficient procedure for transferring specific human genes into Chinese hamster cell mutants: Interspecific transfer of the human genes encoding leucyl-and asparaginyl-tRNA synthetases, Mol. Cell. Biol. 3: 892–902.

    PubMed  CAS  Google Scholar 

  • Cone, R. D., and Mulligan, R. C., 1984, High efficiency gene transfer into mammalian cells: Generation of helper-free recombinant retrovirus with broad mammalian host range, Proc. Natl. Acad. Sci. U.S.A. 81: 6349–6353.

    Article  PubMed  CAS  Google Scholar 

  • Degnen, G. E., Miller, I. L., Eisenstadt, J. M., and Adelberg, E. A., 1976, Chromosome-mediated gene transfer between closely related strains of cultured mouse cells, Proc. Natl. Acad. Sci. U.S.A. 73: 2838–2842.

    Article  PubMed  CAS  Google Scholar 

  • Fournier, R. E. K., 1983, Microcell-mediated chromosome transfer, in: Techniques in Somatic Cell Genetics ( J. M. Shay, ed.), pp. 309–327, Plenum Press, New York.

    Google Scholar 

  • Gerhard, D. S., Kawasaki, E. S., Bancroft, F. C., and Szabo, P., 1981, Localization of a unique gene by direct hybridization in situ, Proc. Natl. Acad. Sci. U.S.A. 78: 3755–3759.

    Article  PubMed  CAS  Google Scholar 

  • Glaser, T., and Housman, D., 1984, Insertion of a selectable marker into various sites on human chromosome #11, 1CSU Short Reports, Vol. 1, pp. 174–175

    Google Scholar 

  • Miami Winter Symposium. Graham, F. L., and van der Eb, A., 1973, A new technique for the assay of infectivity of human adenovirus 5 DNA, Virology 52: 456–467.

    Google Scholar 

  • Gusella, J. F., Keys, C., Varsanyi-Breiner, A., Kao, F.-T., Jones, C., Puck, T. T., and Housman, D., 1980, Isolation and localization of DNA segments from specific human chromosomes, Proc. Natl. Acad. Sci. U.S.A. 77: 2829–2833.

    Article  PubMed  CAS  Google Scholar 

  • Gusella, J. F., Jones, C., Kao, F.-T., Housman, D., and Puck, T. T., 1982, Genetic fine-structure mapping in human chromosome 11 by use of repetitive DNA sequences, Proc. Natl. Acad. Sci. U.S.A. 79: 7804–7808.

    Article  PubMed  CAS  Google Scholar 

  • Gusella, J. F., Wexler, N. S., Conneally, P. M., Naylor, S. L., Anderson, M. A., Tanzi, R. E., Watkins, P. C., Ottina, K., Wallace, M. R., Sakaguchi, A. Y., Young, A. B., Shoulson, I., Bonilla, E., and Martin, J. B., 1983, A polymorphic DNA marker genetically linked to Huntington’s disease, Nature (London) 306: 234–238.

    Article  CAS  Google Scholar 

  • Gusella, J. F., Tanzi, R. E., Anderson, M. A., Hobbs, W., Gibbons, K., Raschtchian, R., Gilliam, T. C., Wallace, M. R., Wexler, N. S., and Conneally, P. M., 1984, DNA markers for nervous system diseases, Science 225: 1320–1326.

    Article  PubMed  CAS  Google Scholar 

  • Haber, D. A., and Schimke, R. T., 1982, Chromosome-mediated transfer and amplification of an altered mouse dihydrofolate reductase gene, Somat. Cell Genet. 8: 499–508.

    Article  PubMed  CAS  Google Scholar 

  • Hartley, J. W., and Rowe, W. P., 1976, Naturally occurring mutine leukemia viruses in wild mice: Characterization of a new “amphotropic” class, J. Virol. 19: 19–25.

    PubMed  CAS  Google Scholar 

  • Hood, L., Steinmetz, M., and Malissen, D., 1983, Genes of the major histocompatibility complex of the mouse, Annu. Rev. Immunol. 1: 529–568.

    Article  PubMed  CAS  Google Scholar 

  • Housman, D., Nelson, D. L., Albritton, L. M., Minden, M., Wieder, S., and Mulligan, R. C., 1983, Gene mapping by metaphase chromosome transfer: Use of an inserted bacterial gene as a selectable marker, in: Banbury Report No. 14 ( C. T. Caskey and R. L. White, eds.), pp. 197–203, Cold Spring Harbor Press, Cold Spring Harbor, New York.

    Google Scholar 

  • Hudson, L. D., Erbe, R. W., and Jacoby, L. B., 1980, Expression of the human argininosuccinate synthetase gene in hamster transferents, Proc. Natl. Acad. Sci. U.S.A. 77: 4234–4238.

    Article  PubMed  CAS  Google Scholar 

  • Ishiura, M., Hirose, S., Uchida, T., Hamada, Y., Suzuki, Y., and Okada, Y., 1982, Phage particle-mediated gene transfer to cultured mammalian cells, Mol. Cell. Biol. 2: 607–616.

    PubMed  CAS  Google Scholar 

  • Klobutcher, L. A., and Ruddle, F. H., 1979, Phenotype stabilisation and integration of transferred material in chromosome-mediated gene transfer, Nature (London) 280: 657–660.

    Article  CAS  Google Scholar 

  • Klobutcher, L. A., Miller, C. L., and Ruddle, F. H., 1980, Chromosome-mediated gene transfer results in two classes of unstable transformants, Proc. Natl. Acad. Sci. U.S.A. 77: 3610–3614.

    Article  PubMed  CAS  Google Scholar 

  • Law, M. L., Davidson, J. N., and Kao, F.-T., 1982, Isolation of a human repetitive sequence and its application to regional chromosome mapping, Proc. Natl. Acad. Sci. U.S.A. 79: 7390–7394.

    Article  PubMed  CAS  Google Scholar 

  • Lewis, W. H., Srinivasan, P. R., Stokoe, N., and Siminovitch, L., 1980, Parameters governing the transfer of the genes for thymidine kinase and dihydrofolate reductase into mouse cells using metaphase chromosomes or DNA, Somat. Cell Genet. 6: 333–347.

    Article  PubMed  CAS  Google Scholar 

  • Lugo, T. G., and Baker, R. M., 1983, Chromosome-mediated gene transfer of HPRT and APRT in an intraspecific human cell system, Somat. Cell Genet. 9: 175–188.

    Article  PubMed  CAS  Google Scholar 

  • Maitland, N. J., and McDougall, J. K., 1977, Biochemical transformation of mouse cells by fragments of herpes simplex virus DNA, Cell 11: 233–241.

    Article  PubMed  CAS  Google Scholar 

  • Mann, R., Mulligan, R. C., and Baltimore, D., 1983, Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus, Cell 33: 153–159.

    Article  PubMed  CAS  Google Scholar 

  • McBride, O. W., and Ozer, H. L., 1973, Transfer of genetic information by purified metaphase chromosomes, Proc. Natl. Acad. Sci. U.S.A. 70: 1258–1262.

    Article  PubMed  CAS  Google Scholar 

  • Miller, C. L., and Ruddle, F. H., 1978, Co-transfer of human X-linked markers into murine somatic cells via isolated metaphase chromosomes, Proc. Natl. Acad. Sci. U.S.A. 75: 3987–3990.

    Google Scholar 

  • Mulligan, R. C., 1983, Construction of highly transmissible mammalian cloning vehicles derived from murine retroviruses, in: Experimental Manipulation of Gene Expression ( M. Inouye, ed.), pp. 155–173, Academic Press, New York.

    Google Scholar 

  • Mulligan, R. C., and Berg, P., 1980, Expression of a bacterial gene in mammalian cells, Science 209: 1422–1427.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, P. D., Miller, C. L., and Ruddle, F. H., 1985, Quantitation of the transgenome size in chromosome-mediated gene transfer lines, Cytogenet. Cell Genet. 39: 125–133.

    Article  PubMed  CAS  Google Scholar 

  • Murray, J. M., Davies, K. E., Harper, P. S., Meredith, L., Mueller, C. R., and Williamson, R., 1982, Linkage relationship of a cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy, Nature (London) 300: 69–71.

    Article  CAS  Google Scholar 

  • Nelson, D. L., Weis, J. H., Przyborski, M. J., Mulligan, R. C., Seidman, J. G., and Housman, D. E., 1984, Metaphase chromosome transfer of introduced selectable markers, J. Mol. Appl. Genet. 2: 563–577.

    Google Scholar 

  • Nelson, D. L., Przyborski, M. J., Housman, D. E., Seidman, J. G., and Weis, J. H., 1986, Insertion of a retroviral vector between the K and 1 region of the murine histocompatibility complex (submitted).

    Google Scholar 

  • Oie, H. K., Russell, E. K., Dotson, J. H., Rhoads, J. M., and Gazdar, A. F., 1976, Host-range properties of murine xenotropic and ecotropic type-C viruses, J. Natl. Cancer Inst. 56: 423–426.

    PubMed  CAS  Google Scholar 

  • Olsen, A. S., McBride, O. W., and Moore, D. E., 1981, Number and size of human X chromosome fragments transferred to mouse cells by chromosome-mediated gene transfer, Mol. Cell. Biol. 1: 439–448.

    PubMed  CAS  Google Scholar 

  • Pellicer, A., Wigler, M., Axel, R., and Silverstein, S., 1978, The transfer and stable integration of the HSV-thymidine kinase gene into mouse cells, Cell 14: 133–141.

    Article  PubMed  CAS  Google Scholar 

  • Rein, A., Schultz, A. M., Bader, J. P., and Bassin, R. H., 1982, Inhibitors of glycosylation reverse retroviral interference, Virology 119: 185–192.

    Article  PubMed  CAS  Google Scholar 

  • Scangos, G. A., Huttner, K. M., Silverstein, S., and Ruddle, F. H., 1979, Molecular analysis of chromosome-mediated gene transfer, Proc. Natl. Acad. Sci. U.S.A. 76: 3987–3990.

    Article  PubMed  CAS  Google Scholar 

  • Schaffner, W., 1980, Direct transfer of cloned genes from bacteria to mammalian cells, Proc. Natl. Acad. Sci. U.S.A. 77: 2163–2167.

    Article  PubMed  CAS  Google Scholar 

  • Sege, R. D., Kozarsky, K., Nelson, D. L., and Krieger, M., 1984, Expression and regulation of human low-density lipoprotein receptors in Chinese hamster ovary cells, Nature (London) 307: 742–745.

    Article  CAS  Google Scholar 

  • Shih, C., and Weinberg, R. A., 1982, Isolation of a transforming sequence from a human bladder carcinoma cell line, Cell 29: 161–169.

    Article  PubMed  CAS  Google Scholar 

  • Shih, C., Shilo, B.-Z., Goldfarb, M. P., Dannenberg, A., and Weinberg, R. A., 1979, Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin, Proc. Natl. Acad. Sci. U.S.A. 76: 5714–5718.

    Article  PubMed  CAS  Google Scholar 

  • Shimotohno, K., and Temin, H. M., 1980, No apparent nucleotide sequence specificity in cellular DNA juxtaposed to retrovirus proviruses, Proc. Natl. Acad. Sci. U.S.A. 77: 7357–7361.

    Article  PubMed  CAS  Google Scholar 

  • Shimotohno, K., and Temin, H. M., 1981, Formation of infectious progeny virus after insertion of herpes simplex thymidine kinase gene into DNA of an avian retrovirus, Cell 26: 67–77.

    Article  PubMed  CAS  Google Scholar 

  • Shoemaker, C. S., Goff, S., Gilboa, E., Paskind, M., Mitra, S. W., and Baltimore, D., 1980, Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: Implication for retrovirus integration, Proc. Natl. Acad. Sci. U.S.A. 77: 3932–3936.

    Article  PubMed  CAS  Google Scholar 

  • Shoemaker, C., Hoffmann, J., Goff, S. P., and Baltimore, D., 1981, Intramolecular integration within Moloney murine leukemia virus DNA, J. Virol. 40: 164–172.

    PubMed  CAS  Google Scholar 

  • Shows, T. B., Naylor, S. L., and Sakaguchi, A. Y., 1982, Mapping the human genome, cloned genes, DNA polymorphisms, and inherited disease, in: Advances in Human Genetics, Vol. 12 ( H. Harris and K. Hirschhorn, eds.), pp. 341–452, Plenum Press, New York.

    Google Scholar 

  • Simmons, T., Lipman, M., and Hodge, L. D., 1978, Uptake and early fate of metaphase chro- mosomes ingested by the Wi-L2 human lymphoid cell line, Somat. Cell Genet. 4: 55–76.

    Article  PubMed  CAS  Google Scholar 

  • Southern, E. M., 1975, Detection of specific sequences among DNA fragments separated by gel electrophoresis, J. Mol. Biol. 98: 503–517.

    Article  PubMed  CAS  Google Scholar 

  • Southern, P. J., and Berg, P., 1982, Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter, J. Mol. Appl. Genet. 1: 327–341.

    PubMed  CAS  Google Scholar 

  • Szybalski, W., Szybalska, E. H., and Ragni, G., 1962, Genetic studies with human cell lines, Natl. Cancer Inst. Monogr. 7: 75–89.

    Google Scholar 

  • Tabin, C. J., Hoffman, J. W., Goff, S. P., and Weinberg, R. A., 1982, Adaptation of a retrovirus as a eukaryotic vector transmitting the herpes simplex virus thymidine kinase gene, Mol. Cell. Biol. 2: 426–436.

    PubMed  CAS  Google Scholar 

  • Temin, H., and Baltimore, D., 1972, RNA-directed DNA synthesis and RNA tumor viruses, Adv. Virus Res. 17.

    Google Scholar 

  • Weis, J. H., Nelson, D. L., Przyborski, M. J., Mulligan, R. C., Chaplin, D. D., Housman, D. E., and Seidman, J. G., 1984, Eukaryotic chromosome transfer: Linkage of the murine major histocompatibility complex to an inserted dominant selectable marker, Proc. Natl. Acad. Sci. U.S.A. 81: 4879–4883.

    Article  PubMed  CAS  Google Scholar 

  • Weis, J. H., Seidman, J. G., Housman, D. E., and Nelson, D. L., 1986, Eukaryotic chromosome transfer: Production of a murine specific cosmid library from a Neo’ linked fragment of murine chromosome 17, Mol. Cell. Biol. 6: 441–451.

    PubMed  CAS  Google Scholar 

  • Wigler, M., Silverman, S. Lee, L.-S., Pellicer, A., Cheng, Y., and Axel, R., 1977, Transfer of purified herpes virus thymidine kinase genes to cultured mouse cells, Cell 14: 725–731.

    Google Scholar 

  • Wigler, M., Pellicer, S., Silverstein, S., and Axel, R., 1978, Biochemical transfer of single-copy eukaryotic genes using total cellular DNA as donor, Cell 14: 725–731.

    Article  PubMed  CAS  Google Scholar 

  • Wigler, M., Pellicer, S., Silverstein, S., Axel, R., Urlaub, G., and Chasin, L., 1979a, DNA-mediated transfer of the adenine phosphoribosyl transferase locus into mammalian cells, Proc. Natl. Acad. Sci. U.S.A. 76: 1373–1376.

    Article  PubMed  CAS  Google Scholar 

  • Wigler, M., Silverstein, S., Lee, L.-S., Pellicer, A., Cheng, Y., and Axel, R., 1979b, Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells, Cell 14: 725–731.

    Article  Google Scholar 

  • Wigler, M., Sweet, R., Sim, G. K., Wold, B., Pellicer, A., Lacy, E., Maniatis, T., Silverstein, S., and Axel, R., 1979c, Transformation of mammalian cells with genes from prokaryotes and eukaryotes, Cell 16: 777–785.

    Article  PubMed  CAS  Google Scholar 

  • Wigler, M., Perucho, M., Kurtz, K.. Dana, S., Pellicer, A., Axel, R., and Silverstein, S., 1980, Transformation of mammalian cells with an amplifiable dominant-acting gene, Proc. Natl. Acad. Sci. U.S.A. 77: 3567–3570.

    CAS  Google Scholar 

  • Willecke, K., and Ruddle, F. H., 1975, Transfer of the human gene for hypoxanthine phosphoribosyltransferase via isolated human metaphase chromosomes into mouse L-cells, Proc. Natl. Acad. Sci. U.S.A. 72: 1792–1796.

    Article  PubMed  CAS  Google Scholar 

  • Willecke, K., Lange, R., Kruger, A., and Reber, T., 1976, Cotransfer of two linked human genes into cultured mouse cells, Proc. Natl. Acad. Sci. U.S.A. 73: 1274–1278.

    Article  PubMed  CAS  Google Scholar 

  • Willing, M. C., Nienhuis, A. W., and Anderson, W. F., 1976, Selective activation of human beta but not gamma globin gene in human fibroblast x mouse erythroleukemia cell hybrids, Nature (London) 277: 534–538.

    Article  Google Scholar 

  • Wright, S., deBoer, E., Grosveld, F. G., and Flavell, R. A., 1983, Regulated expression of the human beta globin gene family in murine erythroleukaemia cells, Nature (London) 305: 333–336.

    Article  CAS  Google Scholar 

  • Wullems, G. J., van der Horst, J., and Bootsma, D., 1976, Transfer of the human X chromosome to human—Chinese hamster cell hybrids via isolated HeLa metaphase chromosomes, Somat. Cell Genet. 2: 359–371.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    David E. Housman

  2. Laboratory of Molecular Genetics, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892, USA

    David L. Nelson

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  1. David E. Housman
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  2. David L. Nelson
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Editors and Affiliations

  1. Center for Genetics, University of Illinois College of Medicine, 60612, Chicago, Illinois, USA

    Raju Kucherlapati

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© 1986 Plenum Press, New York

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Housman, D.E., Nelson, D.L. (1986). Use of Metaphase-Chromosome Transfer for Mammalian Gene Mapping. In: Kucherlapati, R. (eds) Gene Transfer. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5167-2_4

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  • DOI: https://doi.org/10.1007/978-1-4684-5167-2_4

  • Publisher Name: Springer, Boston, MA

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