Genetic studies in familial cases of sex reversal and in human embryos have contributed to the understanding of human sex determination and its disorders. For some heritable disorders of sex reversal, the gonadal phenotype was frequently overlooked until sex reversal was discovered fortuitously by chromosome analysis, often resulting in preventable complications. Within families, the phenotypes are variable and, in some instances, these can be explained by known genetic mechanisms. When a novel molecular marker is shared by family members affected with sex reversal, the level of confidence is higher that this marker may play a role in the development of the phenotype. The identification of pedigrees with sufficient power to generate significant linkage of disorder (lod) scores from genomewide screens can now lead to the identification of novel sex-determining genes. Studies of the gonads of 46,XY human embryos have shown that SOX9 expression follows a pattern similar to that of SRY and, in both instances, stands in contrast to the expression observed in the mouse. Differences between human and mouse embryonic gonads have also been observed for the temporal expression of DAX1, suggesting that the mechanisms of action of SRY, SOX9, and DAX1 may vary between these and other species.
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