Human Genome Meeting 2005

Kyoto International Conference Hall, Kyoto, Japan

April 19, 2005

107/347 (15. Epigenetics and diseases)

Oral and poster presentation

A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 11q

1Yoichi Yamada, 2Tomoyo Shirakawa, 3Todd Taylor, 4Kohji Okamura, 5Hidenobu Soejima, 5Tsunehiro Mukai, 3Yoshiyuki Sakaki, 1Ken-ichiro Muramoto, and 6Takashi Ito 1Kanazawa Univ., Japan, 2Arkray Corporation, Kyoto, Japan, 3Riken, Yokohama, Japan, 4SickKids, Toronto, Canada, 5Saga Univ., Japan, 6Univ. Tokyo, Japan

Approximately half of the human genes have CpG islands (CGIs) around their promoter regions. While CGIs usually escape methylation in normal cells, 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. We previously developed a simple HpaII-McrBC PCR method to discriminate allelic methylation status including the composite pattern, and applied it to all CGIs on human chromosome 21q (Genome Res. 14, 247, 2004). Here, we applied the method to 653 CGIs computationally identified on human chromosome 11q. The analysis revealed that, although most CGIs (543 out of 653) escape methylation, a sizable fraction (86 out of 653) are fully methylated even in normal peripheral blood cells. Notably, fully-methylated CGIs occur much less frequently on 11q than 21q, whereas a comparable density of unmethylated CGIs is shared by the two chromosomes. We also identified six CGIs showing the composite pattern, and demonstrated that one of them is indeed methylated mono-allelically. Further analysis using informative pedigrees revealed that the CGI is subject to paternal allele-specific methylation. The CGI does not lie in the promoter regions of any known or predicted genes. We are thus investigating the allelic expression status of the genes that serve as its nearest neighbors on the current genome map.