A human XY female with a frame shift mutation in the candidate testis-determining gene SRY (original) (raw)

Nature volume 348, pages 452–454 (1990)Cite this article

Abstract

THE primary decision about male or female sexual development of the human embryo depends on the presence of the Y chromosome1'2, more specifically on a gene on the Y chromosome encoding a testis-determining factor, TDF. The human sex-determining region has been delimited to a 35-kilobase interval near the Y pseudoautosomal boundary3. In this region there is a candidate gene for TDF, termed SRY, which is conserved and specific to the Y chromosome in all mammals tested3. The corresponding gene from the mouse Y chromosome is deleted in a line of XY female mutant mice, and is expressed at the expected stage during male gonadal development4. We have now identified a mutation in SRY in one out of 12 sex-inversed XY females with gonadal dysgenesis who do not lack large segments of the short arm of the Y chromosome5-8. The four-nucleotide deletion occurs in a sequence of SRY encoding a conserved DNA-binding motif and results in a frame shift presumably leading to a non-functional protein. The mutation occurred de novo, because the father of the sporadic XY female that bears it has the normal sequence at the corresponding position. These results provide strong evidence for SRY being TDF.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Ford, C. E. Miller, O. J., Polani, P. E., de Almeida, J. C. & Briggs, J. H. Lancet i, 711–713 (1959).
    Article Google Scholar
  2. Jacobs, P. A. & Strong, J. A. Nature 183, 302–303 (1959).
    Article CAS ADS PubMed Google Scholar
  3. Sinclair, A. H. et al. Nature 346, 240–244 (1990).
    Article CAS ADS PubMed Google Scholar
  4. Gubbay, J. et al. Nature 346, 245–250 (1990).
    Article CAS ADS PubMed Google Scholar
  5. Disteche, C. M. et al. Proc. natn. Acad. Sci. U.S.A. 83, 7841–7844 (1986).
    Article CAS ADS Google Scholar
  6. Müller, U., Lalande, M., Donlon, T. Latt, S. A. Nucleic Acids Res. 14, 1325–1340 (1986).
    Article PubMed PubMed Central Google Scholar
  7. Affara, N. A. et al. Nucleic Acids Res. 15, 7325–7342 (1987).
    Article CAS PubMed PubMed Central Google Scholar
  8. Levilliers, J., Quack, B., Weissenbach, J. & Petit, C. Proc. natn. Acad. Sci. U.S.A. 86, 2296–2300 (1989).
    Article CAS ADS Google Scholar
  9. Page, D. C. et al. Cell 51, 1091–1104 (1987).
    Article CAS PubMed Google Scholar
  10. Simpson, J. L., Blagowidow, N. & Martin, A. O. Hum. Genet. 58, 91–97 (1981).
    Article CAS PubMed Google Scholar
  11. Jantzen, H.-M., Admon, Admon, A., Bell, S. P. & Tjian, R. Nature 344, 830–836 (1990).
    Article CAS ADS PubMed Google Scholar
  12. Farabough, P. J., Schmeissner, U., Hofer, M. & Miller, J. H. J. molec. Biol. 126, 847–857 (1978).
    Article Google Scholar
  13. Weber, J. L. & May, P. E. Am. J. hum. Genet. 44, 388–396 (1989).
    CAS PubMed PubMed Central Google Scholar
  14. Schäfer, R., Zischler, H., Birsner, U., Becker, A. & Epplen, J. T. Electrophoresis 9, 369–374 (1988).
    Article PubMed Google Scholar
  15. Casanova, J.-L., Pannetier, C., Jaulin, C., Jaulin, C. & Kourilsky, P. Nucleic Acids Res. 18, 4028 (1990).
    Article CAS PubMed PubMed Central Google Scholar

Download references

Author information

Authors and Affiliations

  1. Institute of Human Genetics, University of Freiburg, Breisacherstrasse 33, W-7800, Freiburg i.Br, Germany
    Ralf J. Jäger & Gerd Scherer
  2. Department of Clinical Genetics, Karolinska Hospital, PO Box 60500, S-10401, Stockholm, Sweden
    Maria Anvret
  3. Department of Endocrinology, Karolinska Hospital, PO Box 60500, S-10401, Stockholm, Sweden
    Kerstin Hall

Authors

  1. Ralf J. Jäger
    You can also search for this author inPubMed Google Scholar
  2. Maria Anvret
    You can also search for this author inPubMed Google Scholar
  3. Kerstin Hall
    You can also search for this author inPubMed Google Scholar
  4. Gerd Scherer
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Jäger, R., Anvret, M., Hall, K. et al. A human XY female with a frame shift mutation in the candidate testis-determining gene SRY.Nature 348, 452–454 (1990). https://doi.org/10.1038/348452a0

Download citation

This article is cited by