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.

  • Protocol
  • Published:

Computational screening of conserved genomic DNA in search of functional noncoding elements

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: The main display of the UCSC Genome Browser8.
Figure 2: The UCSC Table Browser10 main page.

References

  1. Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002).

  2. Bejerano, G. et al. Ultraconserved elements in the human genome. Science 304, 1321–1325 (2004).

    Article  CAS  Google Scholar 

  3. Ovcharenko, I., Stubbs, L. & Loots, G.G. Interpreting mammalian evolution using Fugu genome comparisons. Genomics 84, 890–895 (2004).

    Article  CAS  Google Scholar 

  4. Woolfe, A. et al. Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol. 3, e7 (2004).

    Article  Google Scholar 

  5. Bejerano, G., Haussler, D. & Blanchette, M. Into the heart of darkness: large-scale clustering of human non-coding DNA. Bioinformatics 20 (suppl. 1), I40–I48 (2004).

    Article  CAS  Google Scholar 

  6. Dermitzakis, E.T., Reymond, A. & Antonarakis, S.E. Conserved non-genic sequences—an unexpected feature of mammalian genomes. Nat. Rev. Genet. 6, 151–157 (2005).

    Article  CAS  Google Scholar 

  7. Glazov, E.A., Pheasant, M., McGraw, E.A., Bejerano, G. & Mattick, J.S. Ultraconserved elements in insect genomes: a highly conserved intronic sequence implicated in the control of homothorax mRNA splicing. Genome Res. (in the press).

  8. Kent, W.J. et al. The human genome browser at UCSC. Genome Res. 12, 996–1006 (2002).

    Article  CAS  Google Scholar 

  9. Papatsenko, D. & Levine, M. Computational identification of regulatory DNAs underlying animal development. Nat. Methods 2, 529–534 (2005).

    Article  CAS  Google Scholar 

  10. Karolchik, D. et al. The UCSC Table Browser data retrieval tool. Nucleic Acids Res. 32, 493–496 (2004).

    Article  Google Scholar 

  11. Kent, W.J., Baertsch, R., Hinrichs, A., Miller, W. & Haussler, D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc. Natl. Acad. Sci. 100, 11484–11489 (2003).

    Article  CAS  Google Scholar 

  12. Kent, W.J. BLAT—the BLAST-like alignment tool. Genome Res. 12, 656–664 (2002).

    Article  CAS  Google Scholar 

  13. Kent, W.J. et al. Exploring relationships and mining data with the UCSC Gene Sorter. Genome Res. 15, 737–741 (2005).

    Article  CAS  Google Scholar 

  14. McGinnis, S. & Madden, T.L. BLAST: at the core of a powerful and diverse set of sequence analysis tools. Nucleic Acids Res. 32, 20–25 (2004).

    Article  Google Scholar 

  15. Kanz, C. et al. The EMBL Nucleotide Sequence Database. Nucleic Acids Res. 33, D29–D33 (2005).

    Article  CAS  Google Scholar 

  16. Tompa, M. et al. Assessing computational tools for the discovery of transcription factor binding sites. Nat. Biotechnol. 23, 137–144 (2005).

    Article  CAS  Google Scholar 

  17. Gardner, P.P. & Giegerich, R. A comprehensive comparison of comparative RNA structure prediction approaches. BMC Bioinformatics 5, 140 (2004).

    Article  Google Scholar 

  18. Glazko, G.V., Koonin, E.V., Rogozin, I.B. & Shabalina, S.A. A significant fraction of conserved noncoding DNA in human and mouse consists of predicted matrix attachment regions. Trends Genet. 19, 119–124 (2003).

    Article  CAS  Google Scholar 

  19. Boffelli, D. et al. Phylogenetic shadowing of primate sequences to find functional regions of the human genome. Science 299, 1391–1394 (2003).

    Article  CAS  Google Scholar 

  20. Ahituv, N., Rubin, E.M. & Nobrega, M.A. Exploiting human–fish genome comparisons for deciphering gene regulation. Hum. Mol. Genet. 13 (special issue 2), 261–266 (2004).

    Article  Google Scholar 

  21. Kleinjan, D.A. & van Heyningen, V. Long-range control of gene expression: emerging mechanisms and disruption in disease. Am. J. Hum. Genet. 76, 8–32 (2005).

    Article  CAS  Google Scholar 

  22. Margulies, E.H., Blanchette, M., Haussler, D. & Green, E.D. Identification and characterization of multi-species conserved sequences. Genome Res. 13, 2507–2518 (2003).

    Article  CAS  Google Scholar 

  23. Cooper, G.M. et al. Characterization of evolutionary rates and constraints in three Mammalian genomes. Genome Res. 14, 539–548 (2004).

    Article  CAS  Google Scholar 

  24. Nobrega, M.A., Ovcharenko, I., Afzal, V. & Rubin, E.M. Scanning human gene deserts for long-range enhancers. Science 302, 413 (2003).

    Article  CAS  Google Scholar 

  25. Levine, M. & Tjian, R. Transcription regulation and animal diversity. Nature 424, 147–151 (2003).

    Article  CAS  Google Scholar 

  26. Bondarenko, V.A., Liu, Y.V., Jiang, Y.I. & Studitsky, V.M. Communication over a large distance: enhancers and insulators. Biochem. Cell Biol. 81, 241–251 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the UCSC Genome Browser staff for continuously developing and maintaining the infrastructure on which this protocol relies. We also thank N. Ahituv for critically reading the manuscript and M. Nobrega for advice. A.C.S. is supported by the Graduate Research and Education in Adaptive bio-Technology (GREAT) Training Program of the UC Systemwide Biotechnology Research and Education Program, grant #2004-33. D.H. and G.B. are supported by a US National Human Genome Research Institute grant P41 HG002371. D.H. is also supported by a Howard Hughes Medical Institute grant.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gill Bejerano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bejerano, G., Siepel, A., Kent, W. et al. Computational screening of conserved genomic DNA in search of functional noncoding elements. Nat Methods 2, 535–545 (2005). https://doi.org/10.1038/nmeth0705-535

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth0705-535

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