Identifying genes for male sex determination in humans

The convergence of genetic and molecular technologies has led to the identi fication of a number of genes for male sex determination. The observation o f chromosomal translocations, deletions, and duplications in sex reversed i ndividuals was instrumental for the positional cloning of SRY, SOX9, WT1, a nd DAX1. Cloning by protein-DNA interaction was required for the identifica tion of SF1. The observation of an extended phenotype for the alpha thalass emia-mental retardation syndrome assigned a role for XH2 in the testicular determining process. Over the next several years, new sex determining genes will be identified by linkage analysis in large families with multiple sex reversed members, comparative genomic hybridization of sex reversed indivi duals, and database searches for genes that encode interacting proteins or paralogs of other species. Given the apparent differences in the sex determ ining mechanisms of even closely related species, the roles of all of these genes will require confirmation by demonstrating expression in human gonad al ridge at the critical time, and that mutations result in sex reversal. J . Exp. Zool. 290:567-573, 2001. (C) 2001 Wiley-Liss, Inc.