We next explored sex-biased DEU using a sliding window algorithm and splicing t-test model (FDR<0.01 and splicing index>2; Supplementary Information 6.6). We identified 155 genes (145 autosomal) that displayed sex-biased expression of probe sets encoding one or a subset of exons (Supplementary Table 8) in one or multiple regions/NCX areas. These included several members of the collagen family of genes (COL1A1, COL1A2, COL3A1, COL5A2, and COL6A3), C3, KCNH2 (a gene associated with schizophrenia25), NOTCH3 (a gene mutated in a common form of hereditary stroke disorder26), ELN (a gene located within the Williams syndrome critical region27), and NLGN4X (a X chromosome gene implicated in synapse function and associated with ASD and moderate X-linked intellectual disability11,28). Although comparably expressed in males and females at the population and gene-level (Supplementary Fig. 17), NLGN4X exhibited a significant male-bias in expression of exon 7 and, to a lesser extent, exons 1, 5 and 6 in a developmentally regulated manner (Fig. 3). Together, these findings show that developmentally and spatially regulated differences in gene- and exon-level expression exist between male and female brains.
