Patterns of Sex-Biased Gene Expression in the Human Brain

Schizophrenia is a disease that affects 15.2/100,000 US citizens, with about 0.6-1.9% of the total population being afflicted with some range of severity of the disease. A lot of research has been done on the progression of the disease and its differences between males and females; however, the true underlying cause of the disease remains unknown. In the literature, however, there is a lot of indication that a genetic cause for schizophrenia is the primary origin for the disorder. In order to establish a foundation in differential gene expression and isoform expression between males and females, we utilized the Genotype-Tissue Expression Project data set (which contains samples from healthy individuals at their time of death) for the amygdala, anterior cingulate cortex, and frontal cortex. We performed quality control on the data with Trimmomatic and visualized it with FastQC and MultiQC. We then aligned to a sex-specific reference genome with Hisat2. Finally, we performed a differential expression analysis dthrough the limma/voom package with inputs from featureCounts. An isoform level analysis was run on the anterior cingulate cortex with the IsoformSwitchAnalyzeR package. We were able to identify a few differentially expressed genes in the three tissue sites, which included XIST and other highly conserved, Y-linked genes. As for the isoform level analysis, we were able to identify 13 genes with significant levels of differential isoform usage and expression, two of which have clinical relevance (DAB1 and PACRG). These findings will allow for a comparison to be made by future studies on gene expression in brain tissue samples from patients that had been diagnosed with schizophrenia in their life. By identifying any unique genes in these patients, gene therapies can be developed to target and correct any misexpression that may be occurring.