3.6. Blood−Brain Comparison
We extracted from exon array analysis the three MHC II mRNA expression levels for HLA-DPA1, CD74, and HLA-DRB1 from 187 different samples that had been run in-house for a variety of experiments. Those samples are broadly categorized as brain (n = 29); whole blood and PBMC (n = 84); and LCLs (n = 74) (Table 12 shows details for each category). These three tissues were summarized for exon array expression (brain, transformed cell lines, and non-transformed cells) and the results are shown in Figure 9 A,B,C. As expected, both transformed and non-transformed cells show almost identical expression levels, and were significantly increased from 4–16 times higher expression compared to brain. To determine that residual blood levels were not affecting the brain levels measured by exon array, a series of three brains were measured by analogous rat exon array, with one brain cleared with saline rinse perfusion via carotid artery. The brain levels of three MHC Class II molecules were not altered by perfusion, thus indicating that brain levels, although lower than blood levels, were not the result of residual amounts of blood within the brain.
The HLA-DPA1 gene is located at the edge of the strong MHC association signal to schizophrenia [18] shown in Figure 10. A highly significant SNP associated with schizophrenia is 15 kB downstream of the eQTL for HLA-DPA1 and D’ is 0.82 between rs112790520, a proxy for rs155327711, and rs9277341. The complete absence of HLA-DPA1 gene expression in cortex from fetal cortical samples, and near absence in infant cortex by RNA-Seq [34], is contrasted to later developmental epochs (child, teen, adult, and elderly) that show high levels of HLA-DPA1 (at FWER < 5%).