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Semin Reprod Med 2002; 20(3): 157-168
DOI: 10.1055/s-2002-35380
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Molecular Genetics of Sex Determination

Corinne Cotinot1 , Eric Pailhoux1 , Francis Jaubert2 , Marc Fellous3
  • 1Unité de Biologie du Développement et Biotechnologies, INRA, Jouy en Josas, France
  • 2Université René Descartes, CHU Necker, Hôpital Necker Enfants-Malades APHP, Service d'AnatomoCytoPathologie, Paris, France
  • 3University of Paris 7, Department of Human Genetics, Institut Pasteur, Paris, France
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Publication History

Publication Date:
12 November 2002 (online)

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ABSTRACT

In humans, the choice between male or female development is genetically determined. Sex determination take place when the bipotential embryonic gonad becomes either testis or ovary. This process is directed by genes that have been discovered by genetic analysis of sex-reversed patients and confirmed by knockout experiments in mice. The testis-determining pathway is better known than the ovary pathway. SRY, a gene located on the Y chromosome, triggers a complex genetic cascade leading to testicular differentiation. In this cascade, two genes play a crucial role in male differentiation, SOX9 and FGF9, which contribute to testicular cord formation. However, only a minority of 46,XY sex-reversed patients can be explained by mutations in known genes such as SRY, SOX9, WTI, and SF1, suggesting that other genes influencing sex determination are yet to be discovered. In females, some rare genes that induce ovarian failure or female-to-male sex reversal have been found through gene-targeted inactivation in mice or positional cloning of mutations in humans and goats. In both sexes, genetic analysis of sex-reversed individuals (XX males, XX and XY hermaphrodites, and XY with complete or partial dysgenesis) remains an approach of choice to isolate new genes involved in sex determination.

KEYWORDS

Sex determination - testis differentiation - ovarian failure - sex reversal

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