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Nucleic Acids Research 2005 33(9):2908-2916; doi:10.1093/nar/gki609
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Published online 24 May 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

Prevalence of quadruplexes in the human genome

Julian L. Huppert and Shankar Balasubramanian*

University Chemical Laboratory, University of Cambridge Lensfield Road, Cambridge CB2 1EW, UK

*To whom correspondence should be addressed. Tel: +44 1223 336347; Fax: +44 1223 336913; Email: sb10031{at}cam.ac.uk

Received February 8, 2005. Revised April 17, 2005. Accepted May 3, 2005.

Guanine-rich DNA sequences of a particular form have the ability to fold into four-stranded structures called G-quadruplexes. In this paper, we present a working rule to predict which primary sequences can form this structure, and describe a search algorithm to identify such sequences in genomic DNA. We count the number of quadruplexes found in the human genome and compare that with the figure predicted by modelling DNA as a Bernoulli stream or as a Markov chain, using windows of various sizes. We demonstrate that the distribution of loop lengths is significantly different from what would be expected in a random case, providing an indication of the number of potentially relevant quadruplex-forming sequences. In particular, we show that there is a significant repression of quadruplexes in the coding strand of exonic regions, which suggests that quadruplex-forming patterns are disfavoured in sequences that will form RNA.


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