Skip to main content

Thank you for visiting 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.

  • Letter
  • Published:

Genetic evidence equating SRY and the testis-determining factor


THE testis-determining factor gene (TDF) lies on the Y chromosome and is responsible for initiating male sex determination. SRY is a gene located in the sex-determining region of the human and mouse Y chromosomes and has many of the properties expected for TDFl–3 Sex reversal in XY females results from the failure of the testis determination or differentiation pathways. Some XY females, with gonadal dysgenesis, have lost the sex-determining region from the Y chromosome by terminal exchange between the sex chromosomes4 or by other deletions5. If SRY is TDF, it would be predicted that some sex-reversed XY females, without Y chromosome deletions, will have suffered mutations in SRY. We have tested human XY females and normal XY males for alterations in SRY using the single-strand conformation polymorphism assay6,7 and subsequent DNA sequencing. A de novo mutation was found in the SRY gene of one XY female: this mutation was not present in the patient's normal father and brother. A second variant was found in the SRY gene of another XY female, but in this case the normal father shared the same alteration. The variant in the second case may be fortuitously associated with, or predisposing towards sex reversal; the de novo mutation associated with sex reversal provides compelling evidence that SRY is required for male sex determination.

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

Access options

Buy this article

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

Similar content being viewed by others


  1. Sinclair, A. H. ef al. Nature 346, 240-244 (1990).

    Article  ADS  CAS  Google Scholar 

  2. Gubbay, J. et al. Nature 346, 245-250 (1990).

    Article  ADS  CAS  Google Scholar 

  3. Koopman, P., Munsterberg, A., Capel, B., Vivian, N. & Lovell-Badge, R. Nature 348,350-452 (1990).

    Article  ADS  CAS  Google Scholar 

  4. Levilliers, K., Quack, B., Weissenbach, J. & Petit, C. Proc. natn. Acad. Sci. U.S.A. 86, 2296-2300 (1989).

  5. Page, D. C., Fisher, E. M. C., McGillivary, B. & Brown, L. G. Nature 346, 279-281 (1990).

    Article  ADS  CAS  Google Scholar 

  6. Orita, M., Suzuki, Y., Sekiya, T. & Hayashi, K. Genomics 5, 874-879 (1989).

  7. Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K. & Sekiya, T. Proc. natn. Acad. Sci. U.S.A. 86, 2766-2770 (1989).

  8. Wong, Z., Wilson, V., Patel, I., Povey, S. & Jeffreys, A. J. Ann. hum. Genet. 51, 269-288 (1987).

  9. Wong, Z., Wilson, V., Jeffreys, A. J. & Thein, S. L. Nucleic Acids Res. 14, 4605-4616 (1986).

  10. Palmer, M. S. ef al. Nature 342, 937-939 (1989).

    Article  ADS  CAS  Google Scholar 

  11. Eicher, E. M. & Washburn, L. L. A. Rev. Genet. 20, 327-360 (1986).

  12. Goodfellow, P. J. et al. Ann. hum. Genet. 53, 15-22 (1989).

  13. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463-5467 (1977).

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

Berta, P., Hawkins, J., Sinclair, A. et al. Genetic evidence equating SRY and the testis-determining factor. Nature 348, 448–450 (1990).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


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.


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