Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes

Abstract

Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sexchromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.

Effects of gender on nigral gene expression and parkinson disease

“…Not surprisingly the genes with the largest magnitude difference in expression were X-and Y-chromosome linked, i.e. XIST (423 fold, p ≤10E-11) in the females, and RPS4Y in males (31.6 fold, p ≤2.0E-13), both of which have previously been reported as differentially expressed by gender in the mammalian brain (Eriksson et al, 1999;Vawter et al, 2004), and another Y linked gene DDX3Y which was overexpressed in males (111 fold, p ≤8.8E-15).…”

Transcriptional dysregulation in a transgenic model of Parkinson disease

“…This analysis was prompted by the recent observation that gender has a marked effect on gene expression in human dopaminergic SN neurons, influencing the patterns of gene expression in both normal brain and the response to PD (Cantuti-Castelvetri et al, 2007). Other microarray studies have also revealed gender differences in gene expression in normal human brain (Vawter et al, 2004), but there is little additional data available on the interaction of gender and disease state on neuronal gene expression in either humans or animal models. The importance of gender is emphasized by the fact that the incidence of PD is nearly twice that in men as in women (Baldereschi et al, 2000;Van Den Eeden et al, 2003).…”

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders

“…13,33 Microarray data analysis Cohort composition for microarray analysis-A control group analysis was conducted by splitting the controls into subgroups at a median pH of 6.87 and comparing the gene expression profile with PLMfit. This analysis was used to evaluate gene expression results for agonal-pH sensitive genes.…”

“…13,33 Microarray data analysis Probe level model fit for condensation of affymetrix probe data-A robust probe level model (PLM) fits a linear model to Affymetrix microarray probe data and is freely available at http://www.bioconductor.org. A complete description of the PLM fit algorithm is available at http://www.stat.berkeley.edu/users/bolstad/Dissertation/Bolstad_2004_Dissertation.pdf.…”