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Chunk #7 — Sex Effects on Disease Risk through Gene Regulation — Phenotypic consequences of sexually dimorphic gene expression patterns

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Sex-specific genetic architecture of human disease.
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A second interesting observation is that sexually dimorphic gene expression patterns are often tissue-specific25, whereby a gene may be differentially expressed between the sexes in some but not in other tissues. This important observation suggests that a different architecture of regulatory interactions may underlie gene expression patterns in males and females in different tissues. Hence, it is likely that entire regulatory networks may differ between the sexes, interacting with functional genetic variation (such as expression quantitative traits) in a sex-specific manner. Such differences in gene regulation between the sexes may account for genotype–sex interactions that affect other measurable phenotypes as well as disease risk. A clear example of a sex-specific response to an environmental variable was recently provided by Zammaretti et al., who investigated the effects of long-term moderate/high fat diet on mice. They found phenotypic differences between males and females, including differences in gene regulation, following the application of identical diet in the two sexes34.