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Transcript 
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
• 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
Sex determination
Gene dosage compensation
Nguyen DK and Disteche CM, Nat Genet, 2006. 38(1); Straub T and Becker PB, Nat Rev Genet, 2007. 8(1)
The human Y-chromosome
Skaletsky H, Nature, 2003. 423(6942)
Sex steroid hormone receptors (SSHRs)
Growth hormone signalling
Udy GB, PNAS, 1997. 94(14); Choi HK, Endocrinology, 2000.141(9); Tannenbaum GS, Endocrinology, 2001. 142(11)
Other relevant mechanisms
Wiwi CA, Mol Endocrinol, 2004. 18(8); Tullis KM, Endocrinology, 2003. 144(5); Krebs CJ, Genes Dev, 2003. 17(21)
Gene expression profiling
Gene expression profiling studies in rodents
Sexual dimorphisms in the kidney
Fold change > 3
P < 0.001
Rinn JL, Dev Cell, 2004. 6(6)
Gene expression profiling studies on rodents
Sexual dimorphisms in different tissues
Yang X, Genome Res., 2006. 16(8)
Tissue-specificity of sexual dimorphisms
Yang X, Genome Res., 2006. 16(8)
Common sexual dimorphisms
Sexually dimorphic gene families (I)
Sexually dimorphic gene families (II)
Sexually dimorphic gene function
Polyamine biosynthesis in skeletal muscle
Liver Network
Ingenuity Pathway Analysis, Fold change > 2, Dataset from Yang et al. (2006)
Adipose tissue network
Ingenuity Pathway Analysis, Fold change > 2, Dataset from Yang et al. (2006)
Sexual dimorphisms in the heart
Sexual dimorphisms in the heart
Sexual dimorphisms in the heart
Sexual dimorphisms in the heart
Differential expression of prominent genes
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.
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.
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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