Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Long–range mapping of gaps and telomeres with RecA–assisted restriction endonuclease (RARE) cleavage

Nature Genetics volume 6, pages 379–383 (1994)Cite this article

Abstract

RecA–assisted restriction endonuclease (RARE) cleavage is a method to perform sequence–specific cleavage of genomic DNA, and is useful in physical mapping studies. After making two modifications, we have applied this method to mapping large regions of DNA in several cell types, including a notorious gap near the Huntington disease (HD) locus on chromosome 4. RARE cleavage fragments were analysed by pulsed field gel electrophoresis and Southern blotting and the distances between cleavage sites determined with accuracy. Using RARE cleavage, the gap measured was less than 60 kilobases in length. RARE cleavage is also a straightforward technique to map the distance from a marker to a telomere. The terminal 1.7 megabases of several HD and control cell lines were mapped with no large differences between cell lines in this region.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Ferrin, L.J. & Camerini-Otero, R.D. Selective cleavage of human DNA: RecA-Assisted Restriction Endonuclease (RARE) cleavage. Science 254, 1494–1497 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Ferrin, L.J. & Camerini-Otero, R.D. Synaptic complexes and RecA-assisted restriction endonuclease cleavage of DNA. Meth. molec. Genet. 2B (ed. Adolph, K.W.) 57–66 (Academic Press, Orlando, 1993).

    Google Scholar 

  3. Weber, B. et al. Genomlc organization and complete sequence of the human gene encoding the β-subunit of the cGMP phosphodiesterase and its localisation to 4p16.3. Nucl. Acids Res. 19, 6263–6268 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Whaley, W.L. et al. Mapping of cosmid clones in Huntington's disease region of chromosome 4. Somat. Cell molec. Genet. 17, 83–91 (1991).

    Article  CAS  PubMed  Google Scholar 

  5. Bates, G.P. et al. Defined physical limits of the Huntington's disease gene candidate region. Am. J. hum. Genet. 49, 7–16 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Bucan, M. et al. Physical maps of 4p16.3, the area expected to contain the Huntington disease mutation. Genomics 6, 1–15 (1990).

    Article  CAS  PubMed  Google Scholar 

  7. The Hungiton's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72, 971–983 (1993).

    Article  Google Scholar 

  8. van den Engh, G., Sachs, R., & Trask, B.J. Estimating genomic distance from DNA sequence location in cell nuclei by a random walk model. Science 257, 1410–1412 (1992).

    Article  CAS  PubMed  Google Scholar 

  9. Cox, D.R., Burmeister, M., Price, E.R., Kim, S. & Myers, R.M. Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. Science 250, 245–250 (1990).

    Article  CAS  PubMed  Google Scholar 

  10. Bates, G.P. et al. A yeast artificial chromosome telomore clone spanning a possible location of the Huntington disease gene. Am. J. hum. Genet. 46, 762–775 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Gandelman, K., Gibson, L., Meyn, M.S., & Yang-Feng, T.L. Molecular definition of the smallest region of deletion overlap in the Wolf-Hirschhorn syndrome. Am. J. hum. Genet. 51, 571–578 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang, Y. & Schwartz, D.C., Chopped Inserts: a convenient alternative to agarose/DNA inserts or beads. Nucl. Acids Res. 21, 2528 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Altherr, M.R. et al. Radiation hybrid map spanning the Huntington disease gene region on chromosome 4. Genomics 13, 1040–1046 (1992).

    Article  CAS  PubMed  Google Scholar 

  14. Riethman, H.C., Spais, C., Buckingham, J., Grady, D. & Moyzis, R.K. Physical analysis of the terminal 240 kb of DNA from human chromosome 7q. Genomics 17, 25–32 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. Foote, S., Vollrath, D., Hilton, A. & Page, D.C. The human Y chromosome: overlapping DNA clones spanning the euchromatic region. Science 258, 60–66 (1992).

    Article  CAS  PubMed  Google Scholar 

  16. Chumakov, I. et al. Continuum of overlapping clones spanning the entire human chromosome 21q. Nature 359, 380–386 (1992).

    Article  CAS  PubMed  Google Scholar 

  17. Ichikawa, H. et al. A Notl restriction map of the entire long arm of human chromosome 21. Nature Genet. 4, 361–366 (1993).

    Article  CAS  PubMed  Google Scholar 

  18. Patterson, D. Mapping the way ahead. Nature Genet. 4, 323–324 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Schwartz, D.C., Li, X., Hernandez, L.I., Ramnarain, S.P., Huff, E.J. & Wang, Y. Ordered restriction maps of Saccnaromyces cerevisiae chromosomes constructed by optical mapping. Science 262,110–114 (1993).

    Article  CAS  PubMed  Google Scholar 

  20. McCombie, W.R. et al. Expressed genes, Alu repeats, and polymorphisms in cosmids sequenced from 4p16.3. Nature Genet. 1, 348–353 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Scott, H.S. et al. An 86-bp VNTR within IDUA is the basis of the D4S111 polymorphic locus. Genomics 14, 1118–1120 (1992).

    Article  CAS  PubMed  Google Scholar 

  22. Gusella, J.F. et al. Sequence-tagged sites (STSs) spanning 4p16.3 and the Huntington disease candidate region. Genomics 13, 75–80 (1992).

    Article  CAS  PubMed  Google Scholar 

  23. Feinberg, A.P. & Vogelstein, B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6–13 (1983) and 137, 266–267 (1984).

    Article  CAS  PubMed  Google Scholar 

  24. Herrmann, B.G. & Frischauf, A. Isolation of genomic DNA. Meth. Enzymol. 152 (eds Berger, S. L. & Kimmel, A.R.) 180–183 (Academic Press, Orlando, 1987).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Lance J. Ferrin & R. Daniel Camerini-Otero

Authors
  1. Lance J. Ferrin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Daniel Camerini-Otero
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferrin, L., Camerini-Otero, R. Long–range mapping of gaps and telomeres with RecA–assisted restriction endonuclease (RARE) cleavage. Nat Genet 6, 379–383 (1994). https://doi.org/10.1038/ng0494-379

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0494-379

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing