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.

  • Research Article
  • Published:

Accurate sequencing by hybridization for DNA diagnostics and individual genomics

Abstract

Medical DNA diagnostics will increasingly rely on an accurate and inexpensive identification of mutations that affect the function of a gene. To validate diagnostic sequencing by hybridization (SBH), a number of p53 samples were analyzed with the complete set of 8192 noncomplementary 7-mer oligonu-cleotides. In four repeated, blind experiments we accurately sequenced 1.1 kb per each of 12 homozygote and heterozygote samples possessing base substitutions, insertions, and deletions. This SBH variant offers a high throughput platform to inexpensively sequence individual gene or pathogen genome samples within the clinical laboratory setting.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Ko, L.J. and Prives, C. 1996. p53, puzzle and paradigm. Genes Dev. 10: 1054–1072.

    Article  CAS  Google Scholar 

  2. Wall, J., Cai, S., and Chebab, F.F. 1995. A 31-mutation assay for cystic fibrosis testing in the clinical molecular diagnostic laboratory. Hum. Mutat. 5: 333–338.

    Article  CAS  Google Scholar 

  3. Durocher, F., Sharruck-Eidens, D., McClure, M., Labrie, F., Skolnick, M.H.,, Goldgar, D.E., and Simard, J. 1996. Comparison of BRCA1 polymorphisms, rare sequence variants and/or misense mutations in unaffected and breast/ovarian cancer populations. Hum. Mol. Genet. 6: 835–842.

    Article  Google Scholar 

  4. Studencki, A.B. and Wallace, R.B. 1984. Allele-specific hybridization using oligonucleotide probe of very high specific activity: discrimination of human beta A- and S-globin genes. DNA 3: 7–15.

    Article  CAS  Google Scholar 

  5. Okayama, H., Curiel, D.T., Brantly, M.L., Holmes, M.D., and Crystal, R.G. 1984. Rapid, nonradioactive detection of mutations in the human by allele-specific amplification. J. Lab. Clin. Med. 114: 105–113.

    Google Scholar 

  6. Tavtigian, S.V., Oliphant, A., and Shattuck-Eidens, D. In press. Genomic organization, functional analysis and mutation screening of BRCA1 and BRCA2. Accomplishments in Cancer Research 1996. Fortner, J.G. and Sharp, P.A. (eds.) General Motors Cancer Research Foundation, Dallas, TX.

  7. Drmanac, R. and Crkvenjakov, R. 1987. Method of sequencing of genomes by hybridization with oligonucleotide probes. Yugoslav patent application 570/87.

  8. Drmanac, R. and Crkvenjakov, R. 1993. Method of sequencing of genomes by hybridization with oligonucleotide probes. US patent 5,202,231.

  9. Drmanac, R., Labat, I., Brukner, I., and Crkvenjakov, R. 1989. Sequencing of megabase plus DNA by hybridization: Theory of the method. Genomics 4: 114–127.

    Article  CAS  Google Scholar 

  10. Drmanac, R., Drmanac, S., Strezoska, Z., Paunesku, T., Labat, I., Zaremski, M., et al. 1993. DNA sequence determination by hybridization: A strategy for efficient large-scale sequencing. Science 260: 1649–1652.

    Article  CAS  Google Scholar 

  11. Chee, M., Yang, R., Hubbell, E., Berno, A., Huang, X.C., Stern, D., et al. 1996. Accessing genetic information with high-density DNA arrays. Science 274: 610–613.

    Article  CAS  Google Scholar 

  12. Hacia, J.G., Brody, L., Chee, M.S., Fodor, S.P.A. and Colins, S. 1996. Detection of heterozygous mutations in BRCA1 using high density oligonucleotide arrays and two color florescence analysis. Nat. Genet. 14: 441–449.

    Article  CAS  Google Scholar 

  13. Sugimoto, N., Nakano, S., Yoreyama, M. and Haneda, K. 1996. Improved ther-modynamic parameters and helix initiation factor to predict stability of DNA duplexes. Nucl. Acids Res. 24: 4501–4505.

    Article  CAS  Google Scholar 

  14. Thomas, T.C., Schmidt, C., and Neer, E.J. 1993. G-protein alpha-o-subunit: mutation of conserved cysteins identifies a sutaunit contact surface and alters GDP affinity. Proc. Natl. Acad. Sci. USA 90: 10295–10299.

    Article  CAS  Google Scholar 

  15. Drmanac, R., Strezoska, Z., Labat, I., Drmanac, S. and Crkvenjakov, R. 1990. Reliable hybridization of oligonucleotides as short as six nucleotides. DNA Cell Biol. 9: 527–534.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drmanac, S., Kita, D., Labat, I. et al. Accurate sequencing by hybridization for DNA diagnostics and individual genomics. Nat Biotechnol 16, 54–58 (1998). https://doi.org/10.1038/nbt0198-54

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0198-54

This article is cited by

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