Abstract for presentation at 11th International Congress of Human Genetics

In mammals, sex determination orients the development of the undifferentiated and bipotential gonad toward a testicular or ovarian pathway. Sex determination is initiated by the testis-determining factor SRY, localized on the Y chromosome, which triggers a complex network of genes. Disorders of the sex determination pathway result in malformations of the external and/or internal genitalia. They are poorly understood as only a small minority of patients can be explained genetically. Management of these disorders critically depends on a precise diagnosis, which depends in turn on the specific knowledge of their molecular pathophysiology. Identification of novel sex determining genes has traditionally been based on positional cloning strategies in humans. We will analyze the efficiency of animal model approaches, whether by targeting of a specific gene, or by genetic screening. In particular, we will describe a congenic mouse model in which protection from sex reversal is conferred by selection of genomic elements of the 129 mouse strain on B6-YPOS background, normally sensitive to disorders of sex determination. Finally, we will argue that advances in genetics should be reflected in the medical nomenclature describing intersex patients. The current taxonomy is potentially harmful, since it is perceived by patients as derogatory, and since it categorizes the patients in gender categories regardless of their gender identity. We will propose to comprehensively incorporate the most recent genetic findings in the current classification of intersex patients.