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Nucleic Acids Research 2005 33(9):2952-2961; doi:10.1093/nar/gki582
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Published online 23 May 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome

Lawrence E. Heisler1, Dax Torti1, Paul C. Boutros2,3,8, John Watson2,3, Charles Chan1, Neil Winegarden4, Mark Takahashi4, Patrick Yau4, Tim H.-M. Huang5, Peggy J. Farnham6, Igor Jurisica3,7,8, James R. Woodgett3,4,8, Rod Bremner1,9, Linda Z. Penn2,3 and Sandy D. Der1,*

1Department of Laboratory Medicine and Pathobiology, Program in Proteomics and Bioinformatics, University of Toronto Toronto, ON M5S 1A8, Canada 2Division of Cancer Genomics and Proteomics, Ontario Cancer Institute, University Health Network Toronto, ON M5G 2M9, Canada 3Department of Medical Biophysics, University of Toronto Toronto, ON M5G 2M9, Canada 4University Health Network Microarray Centre Toronto, ON M5G 2C4, Canada 5Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University Columbus, OH 43210, USA 6Department of Medical Pharmacology and Toxicology, University of California-Davis Davis, CA 95616, USA 7Department of Computer Science, University of Toronto Toronto, ON M5S 2M9, Canada 8Division of Signaling Biology, Ontario Cancer Institute Toronto, ON M5G 2M9, Canada 9Toronto Western Research Institute Toronto, ON M5T 2S8, Canada

*To whom correspondence should be addressed. Tel: +1 416 978 8878; Fax: +1 416 978 5959; Email: sandy.der{at}utoronto.ca

Received March 15, 2005. Revised April 28, 2005. Accepted April 28, 2005.

An effective tool for the global analysis of both DNA methylation status and protein–chromatin interactions is a microarray constructed with sequences containing regulatory elements. One type of array suited for this purpose takes advantage of the strong association between CpG Islands (CGIs) and gene regulatory regions. We have obtained 20 736 clones from a CGI Library and used these to construct CGI arrays. The utility of this library requires proper annotation and assessment of the clones, including CpG content, genomic origin and proximity to neighboring genes. Alignment of clone sequences to the human genome (UCSC hg17) identified 9595 distinct genomic loci; 64% were defined by a single clone while the remaining 36% were represented by multiple, redundant clones. Approximately 68% of the loci were located near a transcription start site. The distribution of these loci covered all 23 chromosomes, with 63% overlapping a bioinformatically identified CGI. The high representation of genomic CGI in this rich collection of clones supports the utilization of microarrays produced with this library for the study of global epigenetic mechanisms and protein–chromatin interactions. A browsable database is available on-line to facilitate exploration of the CGIs in this library and their association with annotated genes or promoter elements.


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