Saturday, July 07, 2007

Sex-specific genetic networks   posted by p-ter @ 7/07/2007 02:43:00 PM
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It's often assumed that the "wiring systems" of men and women, apart from the obvious differences in reproductive system, are essentially identical. And to a first approximation, that's of course true. But disparities in certain illnesses and quantitative traits suggest subtle differences in male versus female biology, even outside of obvious (i.e. reproduction) or controversial (i.e. neurobiology) areas.

Early last year, for example, a group of researchers took the simple step of dividing their genetic studies on a number of quantitative traits into males and females. Their results were striking: some traits are influenced by different genes in men and women. This is understandable if you consider a trait as being influenced by a network of interacting genes and proteins, along with the environment signals, as opposed to the simple Mendelian one gene-one trait framework. As men and women develop differently, these's no reason to expect that the "key" nodes in the network (with respect to the quantitative trait in question) will be the same in each. And in fact, this study demonstrates that for some traits, they're not.

A new study on liver cancer comes to a similar conclusion from another angle. The certain type of cancer they consider appears much more often in males than in females (in both humans and a mouse model). In their study (in mice, it should be noted) they find the application of the relevant carcinogen leads to increased levels of a certain inflammatory marker in both sexes, but that the increase is much more pronounced in males. Knockouts of the gene for the marker showed no sex differences in cancer rates, suggesting that the difference in response of a single gene in males and females could be responsible for the disparity.

How could such a differential response be mediated? It's hard to say, but I'd guess a subtle difference in transcription network architecture. Small differences in internal networks can lead to large differences in "higher" phenotypes.