Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1993 May;30(5):353–362. doi: 10.1136/jmg.30.5.353

Parental allele specific methylation of the human insulin-like growth factor II gene and Beckwith-Wiedemann syndrome.

H Schneid 1, D Seurin 1, M P Vazquez 1, M Gourmelen 1, S Cabrol 1, Y Le Bouc 1
PMCID: PMC1016368  PMID: 8320696

Abstract

In an attempt to elucidate the role of methylation in parental imprinting at the IGF-II gene locus, for which imprinting has already been described in the mouse, we undertook an allele specific methylation study of the human IGF-II gene (mapped to 11p15.5) in a control population and in patients with Beckwith-Wiedemann syndrome. In control leucocyte DNA (16 unrelated adults and eight families), the maternal allele of the IGF-II gene was specifically hypomethylated, whereas no such allele specific methylation was found for either the insulin or the calcitonin genes which are located in 11p15.5 and 11p15.1, respectively. Furthermore, the IGF-II gene specific hypomethylation was localised on the 5' portion of exon 9. In the patients with Beckwith-Wiedemann syndrome in which the IGF-II gene is thought to be involved and where paternal isodisomy has been described, hypomethylation of the maternal allele was conserved in leucocyte DNA, but abnormal methylation was detected in malformed tissues where the paternal allele was also demethylated. Some specific mechanism linked to methylation therefore seems to be involved in the pathogenesis of Beckwith-Wiedemann syndrome.

Full text

PDF
353

Images in this article

356Image
on p.356
356Image
on p.356
357Image
on p.357
357Image
on p.357
359Image
on p.359
359Image
on p.359
360Image
on p.360
360Image
on p.360

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell G. I., Horita S., Karam J. H. A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes. 1984 Feb;33(2):176–183. doi: 10.2337/diab.33.2.176. [DOI] [PubMed] [Google Scholar]
  2. Bell G. I., Pictet R. L., Rutter W. J., Cordell B., Tischer E., Goodman H. M. Sequence of the human insulin gene. Nature. 1980 Mar 6;284(5751):26–32. doi: 10.1038/284026a0. [DOI] [PubMed] [Google Scholar]
  3. Blatt J., White C., Dienes S., Friedman H., Foley T. P., Jr Production of an insulin-like growth factor by osteosarcoma. Biochem Biophys Res Commun. 1984 Aug 30;123(1):373–376. doi: 10.1016/0006-291x(84)90423-6. [DOI] [PubMed] [Google Scholar]
  4. Cedar H. DNA methylation and gene activity. Cell. 1988 Apr 8;53(1):3–4. doi: 10.1016/0092-8674(88)90479-5. [DOI] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Daughaday W. H., Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev. 1989 Feb;10(1):68–91. doi: 10.1210/edrv-10-1-68. [DOI] [PubMed] [Google Scholar]
  7. DeChiara T. M., Efstratiadis A., Robertson E. J. A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature. 1990 May 3;345(6270):78–80. doi: 10.1038/345078a0. [DOI] [PubMed] [Google Scholar]
  8. DeChiara T. M., Robertson E. J., Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell. 1991 Feb 22;64(4):849–859. doi: 10.1016/0092-8674(91)90513-x. [DOI] [PubMed] [Google Scholar]
  9. Gray A., Tam A. W., Dull T. J., Hayflick J., Pintar J., Cavenee W. K., Koufos A., Ullrich A. Tissue-specific and developmentally regulated transcription of the insulin-like growth factor 2 gene. DNA. 1987 Aug;6(4):283–295. doi: 10.1089/dna.1987.6.283. [DOI] [PubMed] [Google Scholar]
  10. Henry I., Bonaiti-Pellié C., Chehensse V., Beldjord C., Schwartz C., Utermann G., Junien C. Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature. 1991 Jun 20;351(6328):665–667. doi: 10.1038/351665a0. [DOI] [PubMed] [Google Scholar]
  11. Huff K. K., Kaufman D., Gabbay K. H., Spencer E. M., Lippman M. E., Dickson R. B. Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells. Cancer Res. 1986 Sep;46(9):4613–4619. [PubMed] [Google Scholar]
  12. Höppener J. W., Steenbergh P. H., Zandberg J., Bakker E., Pearson P. L., Geurts van Kessel A. H., Jansz H. S., Lips C. J. Localization of the polymorphic human calcitonin gene on chromosome 11. Hum Genet. 1984;66(4):309–312. doi: 10.1007/BF00287635. [DOI] [PubMed] [Google Scholar]
  13. Le Bouc Y., Noguiez P., Sondermeijer P., Dreyer D., Girard F., Binoux M. A new 5'-non-coding region for human placental insulin-like growth factor II mRNA expression. FEBS Lett. 1987 Sep 28;222(1):181–185. doi: 10.1016/0014-5793(87)80216-8. [DOI] [PubMed] [Google Scholar]
  14. Le Moullec J. M., Jullienne A., Chenais J., Lasmoles F., Guliana J. M., Milhaud G., Moukhtar M. S. The complete sequence of human preprocalcitonin. FEBS Lett. 1984 Feb 13;167(1):93–97. doi: 10.1016/0014-5793(84)80839-x. [DOI] [PubMed] [Google Scholar]
  15. Little M., Van Heyningen V., Hastie N. Dads and disomy and disease. Nature. 1991 Jun 20;351(6328):609–610. doi: 10.1038/351609a0. [DOI] [PubMed] [Google Scholar]
  16. Mannens M., Slater R. M., Heyting C., Bliek J., de Kraker J., Coad N., de Pagter-Holthuizen P., Pearson P. L. Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours. Hum Genet. 1988 Dec;81(1):41–48. doi: 10.1007/BF00283727. [DOI] [PubMed] [Google Scholar]
  17. Pettenati M. J., Haines J. L., Higgins R. R., Wappner R. S., Palmer C. G., Weaver D. D. Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Hum Genet. 1986 Oct;74(2):143–154. doi: 10.1007/BF00282078. [DOI] [PubMed] [Google Scholar]
  18. Ping A. J., Reeve A. E., Law D. J., Young M. R., Boehnke M., Feinberg A. P. Genetic linkage of Beckwith-Wiedemann syndrome to 11p15. Am J Hum Genet. 1989 May;44(5):720–723. [PMC free article] [PubMed] [Google Scholar]
  19. Ponder B. Cancer. Gene losses in human tumours. Nature. 1988 Sep 29;335(6189):400–402. doi: 10.1038/335400a0. [DOI] [PubMed] [Google Scholar]
  20. Reeve A. E., Eccles M. R., Wilkins R. J., Bell G. I., Millow L. J. Expression of insulin-like growth factor-II transcripts in Wilms' tumour. Nature. 1985 Sep 19;317(6034):258–260. doi: 10.1038/317258a0. [DOI] [PubMed] [Google Scholar]
  21. Reik W., Collick A., Norris M. L., Barton S. C., Surani M. A. Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature. 1987 Jul 16;328(6127):248–251. doi: 10.1038/328248a0. [DOI] [PubMed] [Google Scholar]
  22. Sapienza C., Peterson A. C., Rossant J., Balling R. Degree of methylation of transgenes is dependent on gamete of origin. Nature. 1987 Jul 16;328(6127):251–254. doi: 10.1038/328251a0. [DOI] [PubMed] [Google Scholar]
  23. Schneid H., Le Bouc Y., Seurin D., Gourmelen M., Cabrol S., Raux-Demay M. C., Girard F., Binoux M. Insulin-like growth factor-I gene analysis in subjects with constitutionally variant stature. Pediatr Res. 1990 May;27(5):488–491. doi: 10.1203/00006450-199005000-00014. [DOI] [PubMed] [Google Scholar]
  24. Schneid H., Seurin D., Noguiez P., Le Bouc Y. Abnormalities of insulin-like growth factor (IGF-I and IGF-II) genes in human tumor tissue. Growth Regul. 1992 Mar;2(1):45–54. [PubMed] [Google Scholar]
  25. Schneid H., Vazquez M. P., Seurin D., le Bouc Y. Loss of heterozygosity in non-tumoral tissue in two children with Beckwith-Wiedemann syndrome. Growth Regul. 1991 Dec;1(4):168–170. [PubMed] [Google Scholar]
  26. Scott J., Cowell J., Robertson M. E., Priestley L. M., Wadey R., Hopkins B., Pritchard J., Bell G. I., Rall L. B., Graham C. F. Insulin-like growth factor-II gene expression in Wilms' tumour and embryonic tissues. Nature. 1985 Sep 19;317(6034):260–262. doi: 10.1038/317260a0. [DOI] [PubMed] [Google Scholar]
  27. Sivasubramanian N., Nayak D. P. Mutational analysis of the signal-anchor domain of influenza virus neuraminidase. Proc Natl Acad Sci U S A. 1987 Jan;84(1):1–5. doi: 10.1073/pnas.84.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Surani M. A., Reik W., Allen N. D. Transgenes as molecular probes for genomic imprinting. Trends Genet. 1988 Mar;4(3):59–62. doi: 10.1016/0168-9525(88)90040-6. [DOI] [PubMed] [Google Scholar]
  29. Tricoli J. V., Rall L. B., Karakousis C. P., Herrera L., Petrelli N. J., Bell G. I., Shows T. B. Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas. Cancer Res. 1986 Dec;46(12 Pt 1):6169–6173. [PubMed] [Google Scholar]
  30. Tricoli J. V., Rall L. B., Scott J., Bell G. I., Shows T. B. Localization of insulin-like growth factor genes to human chromosomes 11 and 12. 1984 Aug 30-Sep 5Nature. 310(5980):784–786. doi: 10.1038/310784a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES