Genetic basis of human sex determination: An overview

Abstract

Mammalian sex determination normally depends on the presence and appropriate expression of the SRY (Sex Determining Region, Y) gene. Mutations in this gene can cause failure of testicular development resulting in male to female sex reversal. However, there is increasing evidence for the existence of X-linked and autosomal genes necessary for sex determination or differentiation. The Steroidogenic factor 1 (SF-1) and Wilms' tumor 1 (WT-1) genes are clearly involved in early gonadal development whilst mutations in the SRY-related gene SOX9 are associated with campomelic dysplasia and XY sex reversal. Pedigree analysis of human SRY-negative XX males suggests the existence of at least one autosomal testis determining locus (TDFA). In addition, rearrangements of chromosomes 9, 10 and the X have occasionally been associated with 46,XY gonadal dysgenesis leading to female gender assignment.