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Identification of Grf1 on mouse chromosome 9 as an imprinted gene by RLGS–M

Nature Genetics volume 14, pages 106–109 (1996)Cite this article

Abstract

Normal mammalian development requires a diploid combination of both haploid parental genomes1. Uniparental disomy for certain segments of specific chromosomes results in aberrant development or prenatal lethality2,3, indicating that the parental genomes have undergone modifications during gametogenesis. These modifications result in parent-of-origin specific expression for some genes, a phenomenon called genomic imprinting. Recent work with DNA methyltransferase deficient mice showed that differential methylation is the probable basis of the imprinted character of several genes4. Screening for endogenous imprinted loci using restriction landmark genomic scanning with methylation sensitive enzymes (RLGS-M) identified eight imprinted RLGS (Irlgs) candidate loci5,6. Molecular analysis of the genomic region of one of the loci (Irigs2) resulted in the discovery of the paternally imprinted U2afbp-rs gene within a previously identified imprinted region on mouse chromosome 11 (refs 5, 7). This paper describes the characterisation of a novel imprinted RLGS-M locus, Irlgs3, on mouse chromosome 9 (ref. 6). Within this locus we identified the Grf1 (also called Cdc25Mm) gene, which is homologous to the RAS-specific guanine nucleotide exchange factor gene, CDC25, in Saccharomyces cerevisiae. Grf1 is located about 30 kb downstream of the methylation imprinted site, identified by RLGS-M, and shows paternal allele specific expression in mouse brain, stomach and heart. Our results indicate that imprinting may have a role in regulating mitogenic signal transduction pathways during growth and development.

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Author notes

  1. Christoph Plass and Hideo Shibata: C.P. & H.S. contributed equally to this work

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263-0001, USA

    Christoph Plass, Iveta Kalcheva, William A. Held & Verne M. Chapman

  2. Genome Science Laboratory, The Institute of Physical and Chemical Research (RIKEN), 3–1–1 Koyadai, Tsukuba City, Ibaraki, 305, Japan

    Hideo Shibata, Shinji Hirotsune, Yasushi Okazaki & Yoshihide Hayashizaki

  3. Center for Genome Research, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh, EH9 3JQ, UK

    Linda Mullins, Nina Kotelevtseva & John Mullins

  4. Institute of Genetic Information, Kyushu University, 3–1–1 Maidashi, Higashiku, Fukuoka, 812, Japan

    Reiko Kato & Hiroyuki Sasaki

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  1. Christoph Plass
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Plass, C., Shibata, H., Kalcheva, I. et al. Identification of Grf1 on mouse chromosome 9 as an imprinted gene by RLGS–M. Nat Genet 14, 106–109 (1996). https://doi.org/10.1038/ng0996-106

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