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. 1989 Jan 11;17(1):271–284. doi: 10.1093/nar/17.1.271

A 12 megabase restriction map at the cystic fibrosis locus.

T R Fulton 1, A M Bowcock 1, D R Smith 1, L Daneshvar 1, P Green 1, L L Cavalli-Sforza 1, H Donis-Keller 1
PMCID: PMC331550  PMID: 2911467

Abstract

We have constructed a physical map of the chromosomal region containing the cystic fibrosis locus using seven DNA markers and pulsed-field gel electrophoresis methods. The map includes cleavage sites for 8 rare-cutting restriction enzymes and spans over 12 megabases (Mb) of DNA, with one unlinked probe covering an additional 5 Mb. To our knowledge, this is the largest segment of human DNA which has been restriction-mapped to date. We can identify thirteen putative HTF islands spaced at intervals of 0.3-3.2 Mb. The region between loci D7S8 and MET, where the CF gene lies, includes 1.4-1.9 Mb of DNA.

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Selected References

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  1. Barker D., Green P., Knowlton R., Schumm J., Lander E., Oliphant A., Willard H., Akots G., Brown V., Gravius T. Genetic linkage map of human chromosome 7 with 63 DNA markers. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8006–8010. doi: 10.1073/pnas.84.22.8006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  3. Bird A., Taggart M., Frommer M., Miller O. J., Macleod D. A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell. 1985 Jan;40(1):91–99. doi: 10.1016/0092-8674(85)90312-5. [DOI] [PubMed] [Google Scholar]
  4. Brown W. R., Bird A. P. Long-range restriction site mapping of mammalian genomic DNA. 1986 Jul 31-Aug 6Nature. 322(6078):477–481. doi: 10.1038/322477a0. [DOI] [PubMed] [Google Scholar]
  5. Burmeister M., Lehrach H. Long-range restriction map around the Duchenne muscular dystrophy gene. Nature. 1986 Dec 11;324(6097):582–585. doi: 10.1038/324582a0. [DOI] [PubMed] [Google Scholar]
  6. Burmeister M., Monaco A. P., Gillard E. F., van Ommen G. J., Affara N. A., Ferguson-Smith M. A., Kunkel L. M., Lehrach H. A 10-megabase physical map of human Xp21, including the Duchenne muscular dystrophy gene. Genomics. 1988 Apr;2(3):189–202. doi: 10.1016/0888-7543(88)90002-x. [DOI] [PubMed] [Google Scholar]
  7. Carle G. F., Frank M., Olson M. V. Electrophoretic separations of large DNA molecules by periodic inversion of the electric field. Science. 1986 Apr 4;232(4746):65–68. doi: 10.1126/science.3952500. [DOI] [PubMed] [Google Scholar]
  8. Carle G. F., Olson M. V. Separation of chromosomal DNA molecules from yeast by orthogonal-field-alternation gel electrophoresis. Nucleic Acids Res. 1984 Jul 25;12(14):5647–5664. doi: 10.1093/nar/12.14.5647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chu G., Vollrath D., Davis R. W. Separation of large DNA molecules by contour-clamped homogeneous electric fields. Science. 1986 Dec 19;234(4783):1582–1585. doi: 10.1126/science.3538420. [DOI] [PubMed] [Google Scholar]
  10. Dean M., Park M., Le Beau M. M., Robins T. S., Diaz M. O., Rowley J. D., Blair D. G., Vande Woude G. F. The human met oncogene is related to the tyrosine kinase oncogenes. 1985 Nov 28-Dec 4Nature. 318(6044):385–388. doi: 10.1038/318385a0. [DOI] [PubMed] [Google Scholar]
  11. Drumm M. L., Smith C. L., Dean M., Cole J. L., Iannuzzi M. C., Collins F. S. Physical mapping of the cystic fibrosis region by pulsed-field gel electrophoresis. Genomics. 1988 May;2(4):346–354. doi: 10.1016/0888-7543(88)90024-9. [DOI] [PubMed] [Google Scholar]
  12. Ehrenberg L., Fedorcsak I., Solymosy F. Diethyl pyrocarbonate in nucleic acid research. Prog Nucleic Acid Res Mol Biol. 1976;16:189–262. doi: 10.1016/s0079-6603(08)60758-8. [DOI] [PubMed] [Google Scholar]
  13. Estivill X., Farrall M., Scambler P. J., Bell G. M., Hawley K. M., Lench N. J., Bates G. P., Kruyer H. C., Frederick P. A., Stanier P. A candidate for the cystic fibrosis locus isolated by selection for methylation-free islands. 1987 Apr 30-May 6Nature. 326(6116):840–845. doi: 10.1038/326840a0. [DOI] [PubMed] [Google Scholar]
  14. Farrall M., Wainwright B. J., Feldman G. L., Beaudet A., Sretenovic Z., Halley D., Simon M., Dickerman L., Devoto M., Romeo G. Recombinations between IRP and cystic fibrosis. Am J Hum Genet. 1988 Oct;43(4):471–475. [PMC free article] [PubMed] [Google Scholar]
  15. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  16. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  17. Gemmill R. M., Coyle-Morris J. F., McPeek F. D., Jr, Ware-Uribe L. F., Hecht F. Construction of long-range restriction maps in human DNA using pulsed field gel electrophoresis. Gene Anal Tech. 1987 Nov-Dec;4(6):119–131. doi: 10.1016/0735-0651(87)90010-0. [DOI] [PubMed] [Google Scholar]
  18. Hardy D. A., Bell J. I., Long E. O., Lindsten T., McDevitt H. O. Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis. Nature. 1986 Oct 2;323(6087):453–455. doi: 10.1038/323453a0. [DOI] [PubMed] [Google Scholar]
  19. Julier C., White R. Detection of a NotI polymorphism with the pmetH probe by pulsed-field gel electrophoresis. Am J Hum Genet. 1988 Jan;42(1):45–48. [PMC free article] [PubMed] [Google Scholar]
  20. Lander E. S., Green P. Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363–2367. doi: 10.1073/pnas.84.8.2363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lathrop G. M., Farrall M., O'Connell P., Wainwright B., Leppert M., Nakamura Y., Lench N., Kruyer H., Dean M., Park M. Refined linkage map of chromosome 7 in the region of the cystic fibrosis gene. Am J Hum Genet. 1988 Jan;42(1):38–44. [PMC free article] [PubMed] [Google Scholar]
  22. Lawrance S. K., Smith C. L., Srivastava R., Cantor C. R., Weissman S. M. Megabase-scale mapping of the HLA gene complex by pulsed field gel electrophoresis. Science. 1987 Mar 13;235(4794):1387–1390. doi: 10.1126/science.3029868. [DOI] [PubMed] [Google Scholar]
  23. Li M., McCann J. D., Liedtke C. M., Nairn A. C., Greengard P., Welsh M. J. Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium. Nature. 1988 Jan 28;331(6154):358–360. doi: 10.1038/331358a0. [DOI] [PubMed] [Google Scholar]
  24. Lindsay S., Bird A. P. Use of restriction enzymes to detect potential gene sequences in mammalian DNA. 1987 May 28-Jun 3Nature. 327(6120):336–338. doi: 10.1038/327336a0. [DOI] [PubMed] [Google Scholar]
  25. Poustka A. M., Lehrach H., Williamson R., Bates G. A long-range restriction map encompassing the cystic fibrosis locus and its closely linked genetic markers. Genomics. 1988 May;2(4):337–345. doi: 10.1016/0888-7543(88)90023-7. [DOI] [PubMed] [Google Scholar]
  26. Quinton P. M. Chloride impermeability in cystic fibrosis. Nature. 1983 Feb 3;301(5899):421–422. doi: 10.1038/301421a0. [DOI] [PubMed] [Google Scholar]
  27. Rappold G. A., Lehrach H. A long range restriction map of the pseudoautosomal region by partial digest PFGE analysis from the telomere. Nucleic Acids Res. 1988 Jun 24;16(12):5361–5377. doi: 10.1093/nar/16.12.5361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Scambler P. J., Wainwright B. J., Watson E., Bates G., Bell G., Williamson R., Farrall M. Isolation of a further anonymous informative DNA sequence from chromosome seven closely linked to cystic fibrosis. Nucleic Acids Res. 1986 Mar 11;14(5):1951–1956. doi: 10.1093/nar/14.5.1951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schwartz D. C., Cantor C. R. Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell. 1984 May;37(1):67–75. doi: 10.1016/0092-8674(84)90301-5. [DOI] [PubMed] [Google Scholar]
  30. Smith C. L., Matsumoto T., Niwa O., Klco S., Fan J. B., Yanagida M., Cantor C. R. An electrophoretic karyotype for Schizosaccharomyces pombe by pulsed field gel electrophoresis. Nucleic Acids Res. 1987 Jun 11;15(11):4481–4489. doi: 10.1093/nar/15.11.4481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spence M. A., Tsui L. C. Report of the committee on the genetic constitution of chromosomes 7, 8 and 9. Cytogenet Cell Genet. 1987;46(1-4):170–187. doi: 10.1159/000132476. [DOI] [PubMed] [Google Scholar]
  32. Tsui L. C., Buchwald M., Barker D., Braman J. C., Knowlton R., Schumm J. W., Eiberg H., Mohr J., Kennedy D., Plavsic N. Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker. Science. 1985 Nov 29;230(4729):1054–1057. doi: 10.1126/science.2997931. [DOI] [PubMed] [Google Scholar]
  33. Vollrath D., Davis R. W. Resolution of DNA molecules greater than 5 megabases by contour-clamped homogeneous electric fields. Nucleic Acids Res. 1987 Oct 12;15(19):7865–7876. doi: 10.1093/nar/15.19.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Vollrath D., Nathans J., Davis R. W. Tandem array of human visual pigment genes at Xq28. Science. 1988 Jun 17;240(4859):1669–1672. doi: 10.1126/science.2837827. [DOI] [PubMed] [Google Scholar]
  35. Wainwright B. J., Scambler P. J., Schmidtke J., Watson E. A., Law H. Y., Farrall M., Cooke H. J., Eiberg H., Williamson R. Localization of cystic fibrosis locus to human chromosome 7cen-q22. 1985 Nov 28-Dec 4Nature. 318(6044):384–385. doi: 10.1038/318384a0. [DOI] [PubMed] [Google Scholar]
  36. White R., Woodward S., Leppert M., O'Connell P., Hoff M., Herbst J., Lalouel J. M., Dean M., Vande Woude G. A closely linked genetic marker for cystic fibrosis. 1985 Nov 28-Dec 4Nature. 318(6044):382–384. doi: 10.1038/318382a0. [DOI] [PubMed] [Google Scholar]
  37. Woolf T., Lai E., Kronenberg M., Hood L. Mapping genomic organization by field inversion and two-dimensional gel electrophoresis: application to the murine T-cell receptor gamma gene family. Nucleic Acids Res. 1988 May 11;16(9):3863–3875. doi: 10.1093/nar/16.9.3863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van Ommen G. J., Verkerk J. M., Hofker M. H., Monaco A. P., Kunkel L. M., Ray P., Worton R., Wieringa B., Bakker E., Pearson P. L. A physical map of 4 million bp around the Duchenne muscular dystrophy gene on the human X-chromosome. Cell. 1986 Nov 21;47(4):499–504. doi: 10.1016/0092-8674(86)90614-8. [DOI] [PubMed] [Google Scholar]

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