There are widespread differences in how genes are expressed in men and women's brains, based on post-mortem adult human brain and spinal cord samples from over 100 individuals analyzed by byscientists at the University College London Institute of Neurology who studied the expression of every gene in 12 brain regions.  

Their paper in Nature Communications found that the way that the genes are expressed in the brains of men and women were different in all major brain regions and these differences involved 2.5% of all the genes expressed in the brain. They specifically looked at the gene NRXN3, which has been implicated in autism. The gene is transcribed into two major forms and the study results show that although one form is expressed similarly in both men and women, the other is produced at lower levels in women in the thalamus. This observation could be important in understanding the higher incidence of autism in males. 

Overall, the study suggests that there is a sex-bias in the way that genes are expressed and regulated, leading to different functionality and differences in susceptibility to brain diseases observed by neurologists and psychiatrists.

Variable dosage compensation between X chromosome genes with Y-linked orthologues. (a) Bar chart to show the expression of NLGN4Y in men in all CNS regions. (b) Bar chart to show the expression of NLGN4X in women (red bars) and men (blue bars) in all CNS regions. (c) Bar chart to show the expression of ZFY in men in all CNS regions. (d) Bar chart to show the expression of ZFX in women (red bars) and men (blue bars) in all CNS regions. (e) Quantitative RT–PCR validation of NLGN4X and NLGN4Y expression in women (red bars) and men (blue bars) in the thalamus. The 2−ΔCt values have been plotted to show relative gene expression levels. (f) Quantitative RT–PCR validation of NLGN4X and NLGN4Y expression in white matter (green bars) and thalamus (purple bars) in males. The 2−ΔCt values have been plotted to show relative gene expression levels. (g) Quantitative RT–PCR validation of ZFX and ZFY expression in women (red bars) and men (blue bars) in the thalamus. The 2−ΔCt values have been plotted to show relative gene expression levels. The error bars in all panels represent the s.e.m. (N=34). Credit and link: 
doi:10.1038/ncomms3771


Dr. Mina Ryten, UCL Institute of Neurology and senior author of the paper, said, "There is strong evidence to show that men and women differ in terms of their susceptibility to neurological diseases, but up until now the basis of that difference has been unclear.

"Our study provides the most complete information so far on how the sexes differ in terms of how their genes are expressed in the brain. We have released our data so that others can assess how any gene they are interested in is expressed differently between men and women."



Citation:Daniah Trabzuni, Adaikalavan Ramasamy, Sabaena Imran, Robert Walker, Colin Smith, Michael E. Weale, John Hardy, Mina Ryten, 'Widespread sex differences in gene expression and splicing in the adult human brain', Nature Communications 4, Article number: 2771, 22 November 2013 doi:10.1038/ncomms3771. Source: University College London