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Trends Endocrinol Metab. 2009 Dec;20(10):471-6. doi: 10.1016/j.tem.2009.06.007. Epub 2009 Sep 23.

Systems biology asks new questions about sex differences.

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Department of Physiological Science, University of California, Los Angeles, CA, USA.


Females and males differ in physiology and in the incidence and progression of diseases. The sex-biased proximate factors causing sex differences in phenotype include direct effects of gonadal hormones and of genes represented unequally in the genome because of their X- or Y-linkage. Novel systems approaches have begun to assess the magnitude and character of sex differences in organization of gene networks on a genome-wide scale. These studies identify functionally related modules of genes that are coexpressed differently in males and females, and sites in the genome that regulate gene networks in a sex-specific manner. Measurement of the aggregate behavior of genes uncovers novel sex differences that can be related more effectively to susceptibility to disease.

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