Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome

Abstract

PRADER-WILLI syndrome (PWS) is the most common form of dysmorphic genetic obesity associated with mental retardation1,2. About 60% of cases have a cytological deletion of chromosome 15q11q13 (refs 2, 3). These deletions occur de novo exclusively on the paternal chromosome4,5. By contrast, Angelman syndrome (AS) is a very different clinical disorder and is also associated with deletions of region 15q11q13 (refs 6–8), indistinguishable from those in PWS6,8 except that they occur de novo on the maternal chromosome6. The parental origin of the affected chromosomes 15 in these disorders could, therefore, be a contributory factor in determining their clinical phenotypes. We have now used cloned DNA markers specific for the 15q11q13 subregion5,9,10 to determine the parental origin of chromosome 15 in PWS individuals not having cytogenetic deletions; these individuals account for almost all of the remaining 40% of PWS cases. Probands in two families displayed maternal uniparental disomy for chromosome 15q11q13. This is the first demonstration that maternal heterodisomy—the presence of two different chromosome 15s derived from the mother—can be associated with a human genetic disease. The absence of a paternal contribution of genes in region 15q11q13, as found in PWS deletion cases4,5, rather than a mutation in a specific gene(s) in this region may result in expression of the clinical phenotype. Thus, we conclude that a gene or genes in region 15q11q13 must be inherited from each parent for normal human development.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Cassidy, S. B. Curr. Problems Pediatr. 14, 1–55 (1984).

    CAS  Article  Google Scholar 

  2. 2

    Butler, M. G. Am. J. med. Genet. (in the press).

  3. 3

    Ledbetter, D. H., Greenberg, F., Holm, V. A. & Cassidy, S. B. Am. J. med. Genet. 28, 779–790 (1987).

    Article  Google Scholar 

  4. 4

    Butler, M. G., Meaney, F. J. & Palmer, C. G. Am. J. med. Genet. 23, 793–809 (1986).

    CAS  Article  Google Scholar 

  5. 5

    Nicholls, R. D. et al. Am. J. med. Genet. 33, 66–77 (1989).

    CAS  Article  Google Scholar 

  6. 6

    Knoll, J. H. M. et al. Am. J. med. Genet. 32, 285–290 (1989).

    CAS  Article  Google Scholar 

  7. 7

    Pembrey, M. et al. J. Med. Genet. 26, 73–77 (1989).

    CAS  Article  Google Scholar 

  8. 8

    Donlon, T. A. Hum. Genet. 80, 322–328 (1988).

    CAS  Article  Google Scholar 

  9. 9

    Donlon, T. A., Lalande, M., Wyman, A., Bruns, G. & Latt, S. A. Proc. natn. Acad. Sci. U.S.A. 83, 4408–4412 (1986).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Tantravahi, U. et al. Am. J. med. Genet. 33, 78–87 (1989).

    CAS  Article  Google Scholar 

  11. 11

    Rich, D. C., Witkowski, C. M., Summers, K. M., van Tuinen, P. & Ledbetter, D. H. Nucleic Acids Res. 16, 8740 (1988).

    CAS  Article  Google Scholar 

  12. 12

    Higgs, D. R. et al. Proc. natn. Acad. Sci. U.S.A. 83, 5165–5169 (1986).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Butler, M. G. & Meaney, F. J. Am. J. med. Genet. 26, 445–455 (1987).

    CAS  Article  Google Scholar 

  14. 14

    Butler, M. G. Am. J. hum. Genet. 45, 140–146 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Engel, E. Am. J. med. Genet. 6, 137–143 (1980).

    CAS  Article  Google Scholar 

  16. 16

    Spence, J. E. et al. Am. J. hum. Genet. 42, 217–226 (1988).

    MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Warburton, D. Am. J. hum. Genet. 42, 215–216 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Solter, D. A. Rev. Genet. 22, 127–146 (1988).

    CAS  Article  Google Scholar 

  19. 19

    Sapienza, C. Annls N. Y. Acad. Sci. (in the press).

  20. 20

    Monk, M. Genes Dev. 2, 921–925 (1988).

    CAS  Article  Google Scholar 

  21. 21

    Holliday, R. Sci. Am. 260, 60–73 (1989).

    CAS  Article  Google Scholar 

  22. 22

    Surani, M. A., Reik, W. & Allen, N. D. Trends Genet. 4, 59–62 (1988).

    CAS  Article  Google Scholar 

  23. 23

    Cedar, H. Cell 53, 3–4 (1988).

    CAS  Article  Google Scholar 

  24. 24

    Kajii, T. & Ohama, K. Nature 268, 633–634 (1977).

    ADS  CAS  Article  Google Scholar 

  25. 25

    Reik, W. J. med. Genet. 25, 805–808 (1988).

    CAS  Article  Google Scholar 

  26. 26

    Reik, W. & Surani, M. A. Nature 338, 112–113 (1989).

    ADS  CAS  Article  Google Scholar 

  27. 27

    Scrable, H. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).

  28. 28

    Voss, R. et al. Am. J. hum. Genet. 45, 373–380 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Yunis, J. J. Science 191, 1268–1270 (1976).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Seabright, M. Lancet ii, 971–972 (1971).

    Article  Google Scholar 

  31. 31

    Lalande, M. et al. Cancer Genet. Cytogenet. 13, 283–295 (1984).

    CAS  Article  Google Scholar 

  32. 32

    Fischel-Ghodsian, N., Nicholls, R. D. & Higgs, D. R. Nucleic. Acids Res. 15, 6197–6207 (1987).

    CAS  Article  Google Scholar 

  33. 33

    Lalande, M., Noolandi, J., Turmel, C., Rousseau, J. & Slater, G. W. Proc. natn. Acad. Sci. U.S.A. 84, 8011–8015 (1987).

    ADS  CAS  Article  Google Scholar 

  34. 34

    Schwartz, D. C. & Cantor, C. R. Cell 37, 67–75 (1984).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nicholls, R., Knoll, J., Butler, M. et al. Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome. Nature 342, 281–285 (1989). https://doi.org/10.1038/342281a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing