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This review discusses the strategies for identifying X and Y genes or mechanisms that cause sexual bias, using mouse models that differ in their sex chromosome complement, including differences in the parental source of the X chromosome.Primary among the sexually unbalanced effects of X and Y genes are those that cause sexual differentiation of the gonads.Here, we review the research strategies to identify the X and Y genes or chromosomal regions that cause direct, sexually differentiating effects on non-gonadal cells.

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These X and Y gene effects are here called “direct” effects of the sex chromosomes, because the sex bias in the X and Y gene expressions acts directly to cause sex differences in non-gonadal tissues instead of indirectly via an action on the gonads to induce sex differences caused by gonadal hormones [].

Historically, it has been much easier to study the effects of gonadal hormones, which can be administered or blocked or withdrawn by simple experimental procedures.

One autosome, the proto-Y chromosome, acquired a dominant male-determining locus, which led to the loss of recombination with the proto-X, and ultimately, to the wholesale loss of gene-encoding DNA from the Y chromosome [].

The X and Y PARs are therefore identical on average between males and females and are not thought to cause sex differences in phenotypes.

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