Skip to main content

Thank you for visiting 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.

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

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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


  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  Google Scholar 

Download references


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


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).

Download citation

  • Issue Date:

  • DOI:

This article is cited by


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