Adult multi sex
In order to explore the possibility of sex-biased gene regulatory architectures we also conducted an expression quantitative trait loci (e QTL) analysis with the aim of finding significant interactions between sex and genotype.
To maximize power, we used paired genotyping and gene-level expression data provided jointly by the North American Brain Expression Consortium and UKBEC.
Hypothalamus (boxed) is the only brain region showing significant sex-biased gene expression.
(c) Gene structure of NRXN3 and expression levels (y axis) plotted for each probe set (x axis) covering NRXN3 in males (blue line) and females (red line) in thalamus.
To address these limitations, we analysed data from the UK Brain Expression Consortium (UKBEC).
This data set is particularly valuable because (i) it is large with post-mortem samples originating from 137 neuropathologically confirmed control individuals (Supplementary Data 1 and 2), (ii) up to 12 central nervous system (CNS) regions have been sampled from each individual and (iii) transcriptome profiling was performed using the Affymetrix Human Exon 1.0 ST Array, which features 1.4 million probe sets assaying expression across each individual exon.
Over 5% of regional findings are validated using q RT–PCR or have supporting evidence in the literature (Supplementary Data 5).(a) Bar chart showing the percentage of expressed genes with evidence of sex-biased expression or splicing in each brain region.However, we verified that none of the findings reported in this study could be accounted for by sex differences in any of these factors (Methods).Sex-biased expression and splicing was investigated in each brain region separately and by averaging gene-level signals across all brain regions.In this way this study provides unequivocal evidence that sex-biased gene expression in the adult human brain is widespread in terms of both the number of genes and range of brain regions involved.We also show that in some specific cases, molecular differences are likely to have functional consequences relevant to human disease and finally that sex biases in expression may reflect sex-biased gene regulatory structures.
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In total we analysed 1,182 post-mortem brain samples dissected from frontal cortex, occipital cortex (BA17, primary visual cortex), temporal cortex, intralobular white matter, thalamus, putamen, substantia nigra, hippocampus, hypothalamus, medulla, cerebellar cortex and spinal cord.