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Nucleic Acids Research 2006 34(9):2663-2675; doi:10.1093/nar/gkl354
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Published online 19 May 2006

© The Author 2006. 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@oxfordjournals.org

Article

Long homopurine•homopyrimidine sequences are characteristic of genes expressed in brain and the pseudoautosomal region

Albino Bacolla, Jack R. Collins1, Bert Gold2, Nadia Chuzhanova3,4, Ming Yi1, Robert M. Stephens1, Stefan Stefanov2, Adam Olsh2, John P. Jakupciak5, Michael Dean2, Richard A. Lempicki6, David N. Cooper4 and Robert D. Wells*

Institute of Biosciences and Technology, Center for Genome Research, Texas A&M University System Health Science Center, Texas Medical Center 2121 West Holcombe Blvd, Houston, TX 77030, USA 1 Advanced Biomedical Computing Center, NCI-Frederick Frederick, MD 21702, USA 2 Laboratory of Genomic Diversity, NCI-Frederick Frederick, MD 21702, USA 3 Biostatistics and Bioinformatics Unit, Cardiff University Cardiff CF14 4XN, UK 4 Institute of Medical Genetics, Cardiff University Heath Park, Cardiff CF14 4XN, UK 5 National Institute of Standards and Technology, DNA Technologies Group, Biotechnology Division Gaithersburg, MD 20899, USA 6 Laboratory of Immunopathogenesis and Bioinformatics, SAIC-Frederick, Inc. Frederick, MD 21702, USA

*To whom correspondence should be addressed. Tel: +1 713 677 7651; Fax: +1 713 677 7689; Email: rwells{at}ibt.tamhsc.edu

Received February 23, 2006. Revised March 13, 2006. Accepted April 20, 2006.

Homo(purine•pyrimidine) sequences (R•Y tracts) with mirror repeat symmetries form stable triplexes that block replication and transcription and promote genetic rearrangements. A systematic search was conducted to map the location of the longest R•Y tracts in the human genome in order to assess their potential function(s). The 814 R•Y tracts with ≥250 uninterrupted base pairs were preferentially clustered in the pseudoautosomal region of the sex chromosomes and located in the introns of 228 annotated genes whose protein products were associated with functions at the cell membrane. These genes were highly expressed in the brain and particularly in genes associated with susceptibility to mental disorders, such as schizophrenia. The set of 1957 genes harboring the 2886 R•Y tracts with ≥100 uninterrupted base pairs was additionally enriched in proteins associated with phosphorylation, signal transduction, development and morphogenesis. Comparisons of the ≥250 bp R•Y tracts in the mouse and chimpanzee genomes indicated that these sequences have mutated faster than the surrounding regions and are longer in humans than in chimpanzees. These results support a role for long R•Y tracts in promoting recombination and genome diversity during evolution through destabilization of chromosomal DNA, thereby inducing repair and mutation.


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