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Letter

A Comprehensive Analysis of Allelic Methylation Status of CpG Islands on Human Chromosome 21q

¹ Division of Genome Biology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan ² Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan ³ Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan ⁴ Genomic Science Center, RIKEN Yokohama Institute, Yokohama 230-0045, Japan ⁵ Division of Molecular Biology and Genetics, Department of Biomolecular Sciences, Saga University Faculty of Medicine, Saga 849-8501, Japan ⁶ Department of Obstetrics and Gynecology, Saga University Faculty of Medicine, Saga 849-8501, Japan ⁷ Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8562, Japan

Approximately half of all human genes have CpG islands (CGIs)around their promoter regions. Although CGIs usually escape methylation, those on Chromosome X in females and those in the vicinity of imprinted genes are exceptions: They have both methylated and unmethylated alleles to display a "composite" pattern in methylation analysis. In addition, aberrant methylation of CGIs is known to often occur in cancer cells. Here we developed a simple HpaII-McrBC PCR method for discrimination of full, null, incomplete, and composite methylation patterns, and applied it to all computationally identified CGIs on human Chromosome 21q. This comprehensive analysis revealed that, although most CGIs (103 out of 149)escape methylation, a sizable fraction (31 out of 149)are fully methylated even in normal peripheral blood cells. Furthermore, we identified seven CGIs showing the composite methylation, and demonstrated that three of them are indeed methylated monoallelically. Further analyses using informative pedigrees revealed that two of the three are subject to maternal allele-specific methylation. Intriguingly, the other CGI is methylated in an allele-specific but parental-origin-independent manner. Thus, the cell seems to have a broader repertoire of methylating CGIs than previously thought, and our approach may contribute to uncover novel modes of allelic methylation.

⁸ Corresponding author.
E-MAIL titolab{at}kenroku.kanazawa-u.ac.jp; FAX 81-76-234-4508.

[Supplemental material is available online at www.genome.org.]

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