Human Genome Meeting 2000
Vancouver Convention and Exhibition Centre, Vancouver, Canada
April 10, 2000
57/296 (8. Genetics of complex traits)
Oral and poster presentation

Comparative genome analysis of the mouse imprinted gene Impact and its nonimprinted human homolog IMPACT
Kohji Okamura1, Yuriko Hagiwara-Takeuchi1, Masahira Hattori2, Yoshiyuki Sakaki1,2, and Takashi Ito1,3
1Hum. Genome Ctr., Inst. Med. Sci., Univ. Tokyo, Japan, 2Hum. Genome Res. Gr., RIKEN Genomic Sci. Ctr., Japan, 3Dept. Mol. Oncology, Cancer Res. Inst., Kanazawa Univ., Japan
Mammalian cells have a pair of genomes, one is maternal and the other is paternal. But not all the genes are expressed equally from both genomes. This parent-of-origin dependent gene expression is termed genomic imprinting, and genes subjected to this unusual expression are called imprinted genes. We previously developed a novel screening for imprinted genes by allelic message display and identified a mouse imprinted gene Impact which encodes a remarkably conserved protein of unknown function. While this gene is paternally expressed, its human homolog IMPACT is not imprinted or expressed biallelically. To reveal the structural basis for the difference in allelic expression between the two species, we elucidated complete nucleotide sequences for both mouse Impact (~38 kb) and human IMPACT (~30 kb) by our unique nested deletion strategy. Sequence comparison revealed that the two genes share a well-conserved exon-intron organization but bear significantly different CpG islands. The mouse island lies in the first intron and contains characteristic tandem repeats. Furthermore, this island serves as a differentially methylated region (DMR) consisting of hypermethylated maternal allele and unmethylated paternal one. Intriguingly, this intronic island is missing from the nonimprinted human IMPACT. Its sole CpG island spans the first exon, lacks any apparent repeats, and escapes methylation on both chromosomes. These results suggest that the intronic DMR plays a crucial role in the imprinting of Impact.