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The insulin–like growth factor type–2 receptor gene is imprinted in the mouse but not in humans

Nature Genetics volume 5, pages 74–78 (1993)Cite this article

Abstract

In mouse, four genes have been found to undergo genomic imprinting resulting in differential expression of maternally and paternally inherited alleles. To determine whether the cognate genes are also subject to imprinting in humans, we have studied allele–specific expression patterns of insulin–like growth factor 2, IGF2–receptor and H19 in human fetal and adult tissues. In keeping with previous findings in mice, our results indicate that in human fetal tissues the paternal H19 allele is inactive. IGF2 is monoallelically expressed in various tissues but surprisingly not in adult human liver. The human IGF2R gene, another classic example of imprinting in mice, was found to be expressed from both alleles. We provide the first direct evidence for differential imprinting in the human and murine genome.

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References

  1. Cattanach, B.M. Chromosome imprinting and its significance for mammalian development. Genome Analysis 2, 41–71 (1991).

    Google Scholar 

  2. Hadchouel, M., Farza, H., Simon, D., Tiollais, P. & Pourcel, C. Maternal inhibition of hepatitis B surface antigen gene expression in transgenic mice correlates with de novo methylation. Nature 329, 454–456 (1987).

    Article  CAS  PubMed  Google Scholar 

  3. Reik, W., Collick, A., Norris, M.L., Barton, S.C. & Surani, M.A. Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature 328, 248–254 (1987).

    Article  CAS  PubMed  Google Scholar 

  4. Reik, W., Howlett, S.K. & Surani, M.A. Imprinting by DNA methylation: From transgenes to endogenous gene sequences. Development (Suppl.) 99–106 (1990).

  5. Sapienza, C., Peterson, A.C., Rossant, J. & Baling, R. Degree of methylation of transgenes is dependent on gamete of origin. Nature 328, 251–254 (1987).

    Article  CAS  PubMed  Google Scholar 

  6. Swain, J.L., Stewart, T.A. & Leder, P. Parental legacy determines methylation and expression of an autosomal transgene: A molecular mechanism for parental imprinting. Cell 50, 719–727 (1987).

    Article  CAS  PubMed  Google Scholar 

  7. Sasaki, H. et al. Inherited type of allelic methylation variations in a mouse chromosome region where an integrated transgene shows methylation imprinting. Development 111, 573–581 (1991).

    CAS  PubMed  Google Scholar 

  8. DeChiara, T.M., Robertson, E.J. & Efstratiadis, A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64, 849–859 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. Barlow, D.P., Stöger, R., Herrmann, B.G., Saito, K. & Schweifer, N. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349, 84–87 (1991).

    Article  CAS  PubMed  Google Scholar 

  10. Bartolomei, M.S., Zemel, S. & Tilghman, S.M. Parental imprinting of the mouse H19 gene. Nature 351, 153–155 (1991).

    Article  CAS  PubMed  Google Scholar 

  11. Leff, S.E. et al. Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. Nature Genet. 2, 259–264 (1992).

    Article  CAS  PubMed  Google Scholar 

  12. Özçelik, T. et al. Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nature Genet. 2, 265–269 (1992).

    Article  PubMed  Google Scholar 

  13. Zhang, Y. & Tycko, B. Monoalieiic expression of the human H19 gene. Nature Genet. 1, 40–44 (1992).

    Article  CAS  PubMed  Google Scholar 

  14. Rainier, S. et al. Relaxation of imprinted genes in human cancer. Nature 362, 747–749 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. Ohlsson, R. et al. IGF2 is parentally imprinted during embryogenesis and in the Beckwith-Wiedemann syndrome. Nature Genet. 4, 94–97 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Giannoukakis, N., Deal, C., Paquette, J., Goodyer, C.G. & Polychronakos, C. Parental genomic imprinting of the human IGF2 gene. Nature Genet. 4, 98–101 (1993).

    Article  CAS  PubMed  Google Scholar 

  17. Ogawa, O. et al. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms'tumour. Nature 362, 749–751 (1993).

    Article  CAS  PubMed  Google Scholar 

  18. Tadokoro, K., Fujii, H., Inoue, T. & Yamada, M. Polymerase chain reaction (PCR) for detection of ApaI polymorphism at the insulin like growth factor II gene (IGF2). Nucl. Acids Res. 19, 6967 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hol, F.A., Geurds, M.P.A., Hamel, B.C.J. & Mariman, E.C.M. Improving the polymorphism content of the 3'UTR of the human IGF2R gene. Molec. Genet. 1, 347 (1992).

    CAS  Google Scholar 

  20. Rachmilewitz, J. et al. Parental imprinting of the human H19 gene. FEBS Lett. 309, 25–28 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Sasaki, H. et al. Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene. Genes Devel. 6, 1843–1856 (1992).

    Article  CAS  PubMed  Google Scholar 

  22. Soares, M.B. et al. Rat insulin-like growth factor II gene. A single gene with two promoters expressing a multitranscript family. J. molec. Biol. 192, 737–752 (1986).

    Article  CAS  PubMed  Google Scholar 

  23. Tricoli, J.V. et al. Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas. Cancer Res. 46, 6169–6173 (1986).

    CAS  PubMed  Google Scholar 

  24. De Pagter-Holthuizen, P., Jansen, M., Van der Kammen, R.A., Schaik, F.M.A. & Sussenbach, J.S. Differential expression of the human insulin-like growth factor II gene. Characterization of the IGF-II mRNAs and an mRNA encoding a putative IGF-II-associated protein. Biochim Biophys. Acta 950, 282–295 (1988).

    Article  CAS  PubMed  Google Scholar 

  25. Holthuizen, P., Van der Lee, F.M., Ikejiri, K., Yamamoto, M. & Sussenbach, J.S. Identification and initial characterization of a fourth leader exon and promoter of the human IGF-II gene. Biochim. Biophys. Acta 1087, 341–343 (1990).

    Article  CAS  PubMed  Google Scholar 

  26. Raizis, A.M., Eccles, M.R. & Reeve, A.E. Structural analysis of the human insulin-like growth factor-ll P3 promoter. Biochem. J. 289, 133–139 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hall, J.G. Genomic imprinting: Review and relevance to human diseases. Am. J. hum. Genet. 46, 857–873 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Forejt, J. & Gregorová, S. Genetic analysis of genomic imprinting: an imprintor-1 gene controls inactivation of the paternal copy of the mouse Tme locus. Cell 70, 443–450 (1992).

    Article  CAS  PubMed  Google Scholar 

  29. Salido, E.C., Passage, M.B., Yen, P.H., Shapiro, L.J. & Mohandas, T.K. An evaluation of the inactive mouse X chromosome in somatic cell hybrids. Somat. Cell. molec. Genet. 19, 65–71 (1993).

    Article  CAS  PubMed  Google Scholar 

  30. Stöger, R. et al. Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell 73, 61–71 (1993).

    Article  PubMed  Google Scholar 

  31. Heutink, P. et al. A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23–qter. Hum. molec. Genet. 1, 7–10 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. Mariman, E.C.M. et al. Analysis of a second family with hereditary non-chromaffin paragangliomas locates the underlying gene at the proximal region of chromosome 11q. Hum. Genet. 91, 357–361 (1993).

    Article  CAS  PubMed  Google Scholar 

  33. Motokura, T. et al. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature 350, 512–515 (1991).

    Article  CAS  PubMed  Google Scholar 

  34. Pericak-Vance, M.A. et al. Tight linkage of apolipoprotein C2 to myotonic dystrophy on chromosome 19. Neurology 36, 1418–1423 (1986).

    Article  CAS  PubMed  Google Scholar 

  35. Haas, O.A., Argyriou-Tirita, A. & Lion, T. Parental origin of chromosomes involved in the translocation t(9;22). Nature 359, 414–416 (1992).

    Article  CAS  PubMed  Google Scholar 

  36. Van Der Mey, A.G.L., Maaswinkel-Mooy, P.D., Cornelisse, C.J., Schmidt, P.H. & van de Kami, J.J.P. Genomic imprinting in hereditary glomus tumours: Evidence for new genetic theory. Lancet 1291–1294 (1989).

  37. Maniatis, T., Fritsch, E.F. & Sambrook, J. Molecular cloning: A laboratory manual (Cold Spring Harbor, New York, 1982).

    Google Scholar 

  38. Ponce, M.R. & Micol, J.L. PCR amplification of long DNA fragments. Nucl. Acids Res. 20, 623 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands

    Vera M. Kalscheuer, Edwin C. Mariman, Marga T. Schepens & Hans-Hilger Ropers

  2. Medical Center of Human Genetics, Philipps-University Marburg, Germany

    Helga Rehder

Authors
  1. Vera M. Kalscheuer
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  2. Edwin C. Mariman
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  3. Marga T. Schepens
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  4. Helga Rehder
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  5. Hans-Hilger Ropers
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Kalscheuer, V., Mariman, E., Schepens, M. et al. The insulin–like growth factor type–2 receptor gene is imprinted in the mouse but not in humans. Nat Genet 5, 74–78 (1993). https://doi.org/10.1038/ng0993-74

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