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Sexually dimorphic gene expression in somatic tissues

Sexually dimorphic gene expression in somatic tissues. J. Isensee and P. Ruiz Noppinger. Center for Cardiovascular Research (CCR), Charite, Berlin Center for Gender in Medicine (GIM), Charite, Berlin Max-Planck Institute for Molecular Genetics (MPIMPG), Berlin. Contents.

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Sexually dimorphic gene expression in somatic tissues

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  1. Sexually dimorphic gene expression in somatic tissues J. Isensee and P. Ruiz Noppinger Center for Cardiovascular Research (CCR), Charite, Berlin Center for Gender in Medicine (GIM), Charite, Berlin Max-Planck Institute for Molecular Genetics (MPIMPG), Berlin

  2. Contents • General aspects of sex determination • Basic mechanisms of sexually dimorphic gene expression - Gene dosage compensation for X-linked genes - Direct and indirect effects of sex steroid hormones • Gene expression profiling approaches and recent studies • Function of sexually dimorphic genes - Gene Ontology Annotation - Pathway analysis • Sexual dimorphisms in the heart • Conclusion and outlook

  3. Sex determination

  4. Gene dosage compensation Nguyen DK and Disteche CM, Nat Genet, 2006. 38(1); Straub T and Becker PB, Nat Rev Genet, 2007. 8(1)

  5. The humanY-chromosome Skaletsky H, Nature, 2003. 423(6942)

  6. Sex steroid hormone receptors (SSHRs)

  7. Growth hormone signalling Udy GB, PNAS, 1997. 94(14); Choi HK, Endocrinology, 2000.141(9); Tannenbaum GS, Endocrinology, 2001. 142(11)

  8. Other relevant mechanisms Wiwi CA, Mol Endocrinol, 2004. 18(8); Tullis KM, Endocrinology, 2003. 144(5); Krebs CJ, Genes Dev, 2003. 17(21)

  9. Gene expression profiling

  10. Gene expression profiling studies in rodents

  11. Sexual dimorphisms in the kidney Fold change > 3 P < 0.001 Rinn JL, Dev Cell, 2004. 6(6)

  12. Gene expression profiling studies on rodents

  13. Sexual dimorphisms in different tissues Yang X, Genome Res., 2006. 16(8)

  14. Tissue-specificity of sexual dimorphisms Yang X, Genome Res., 2006. 16(8)

  15. Common sexual dimorphisms

  16. Sexually dimorphic gene families (I)

  17. Sexually dimorphic gene families (II)

  18. Sexually dimorphic gene function

  19. Polyamine biosynthesis in skeletal muscle

  20. Liver Network Ingenuity Pathway Analysis, Fold change > 2, Dataset from Yang et al. (2006)

  21. Adipose tissue network Ingenuity Pathway Analysis, Fold change > 2, Dataset from Yang et al. (2006)

  22. Sexual dimorphisms in the heart

  23. Sexual dimorphisms in the heart

  24. Sexual dimorphisms in the heart

  25. Sexual dimorphisms in the heart

  26. Differential expression of prominent genes

  27. Conclusions • Sex differences in somatic tissues seem to be wide spread, but of minor extent. • Sexually dimorphic gene expression is highly tissue specific, only few common genes were identified. • Y-linked genes encoded on the X-degenerated region, specific X-linked genes (e.g. Xist) and genes involved in steroid biosynthesis and metabolism represent the most prominent genes with sex-biased expression • In the liver GH signalling is a major trigger of sex-biased gene expression.

  28. Outlook • Better understand the mouse as a model for sex-differences in human disease - age - estrous cycle • Hormonal involvement may be studied in ovariectomized, orchidectomized, and hypophysectomized animals. • Analyze sexual dimorphisms in - tissue-specific knock out mice - consomic strains • Need to link differential gene expression patterns with phenotypic sex differences.

  29. A sustainable annotation of sex-biased gene expression represents a key towards the understanding of basic physiological differences between sexes in the healthy as well as diseased condition.

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