The initial events of mammalian sex determination are genetically determined with SRY as the master regulatory switch that triggers the formation of the testes. Errors in the process of sex-determination are common and can result in a range of phenotypes from complete sex-reversal to minor genital anomalies. Although many of the early cellular and morphological events that occur downstream of SRY action have been characterized (Figure 1), the mechanisms involved in mammalian sex determination is poorly understood. The objective of the unit is to understand reproductive processes by analysing the genetic and epigenetic mechanisms associated with the development of both somatic and germ cell lineages of the mammalian gonad.
Understanding the development of somatic cell lineage of gonad is being achieved by the analysis of patients with DSD (Disorder of Sex Development) phenotypes. The startegy involves comparative genomic hybridization (CGH) to screen for rearrangements associated with DSD and the functional characterisation of pathogenic mutations revealed by Sanger and Next Generation sequencing approaches. This is aimed at both identifying new genetic variants associated with urogenital anomalies and to use these mutations to understand the mechanism of gonad formation and the choice of somatic sex.