January 20, 2006

Sexual dimorphism in gene expression in human brain

From the paper:
Most notably, in man the brain is sexually dimorphic with respect to asymmetry (the cerebral torque) from right frontal to left occipital across the anteroposterior axis (Barrick et al. 2004). Females are more strongly right-handed than males, acquire words more rapidly (Crow et al. 1998) and have faster brain growth (Kretschmann et al. 1979). By contrast, adult brain size is greater in males than females, cerebral asymmetry is more marked, particularly in the posterior part of the brain (Barrick et al. 2004) and there is a modest male superiority for spatial ability. Although most sexual dimorphisms are caused by male and female gonadal secretions, there is evidence for a direct role of sex chromosomes genes in brain sexual differentiation (Carruth et al. 2002; reviewed in Arnold 2004). In this context, an imbalance of PCDH11X/Y products between sexes might be relevant considering that these genes are expressed from early in development (Blanco et al. 2000).
It's nice to see that some women scientists demonstrate their excellence by writing excellent papers about male-female biological differences rather than engage in knee-jerk reactions to legitimate scientific speculation.

Molecular Biology and Evolution (online first)

Inactivation status of PCDH11X: sexual dimorphisms in gene expression levels in brain

Alexandra M. Lopes et al.

Abstract Genes escaping X-inactivation are predicted to contribute to differences in gene dosage between the sexes and are the prime candidates for being involved in the phenotype observed in individuals with X chromosome aneuploidies. Of particular interest is ProtocadherinX (PCDH11X or PCDHX), a recently described gene expressed in brain. In humans, PCDH11X has a homologue on the Y chromosome and is predicted to escape from X-inactivation. Employing bisulphite sequencing analysis we found absence of CpG island methylation on both the active and the inactive X chromosomes, providing a strong indication that PCDH11X escapes inactivation in humans. Furthermore, a sexual dimorphism in levels of expression in brain tissue was observed by quantitative real-time PCR, with females presenting an up to 2-fold excess in the abundance of PCDH11X transcripts. We relate these findings to sexually dimorphic traits in the human brain. Interestingly, PCDH11X/Y gene pair is unique to Homo sapiens, since the X-linked gene was transposed to the Y chromosome after the human–chimpanzee lineages split. Although no differences in promoter methylation were found between humans and chimpanzees, evidence of an upregulation of PCDH11X in humans deserves further investigation.


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