Extended Data Figure 4: RNA expression of C4A and C4B in relation to copy number of C4A, C4B, and the C4–HERV (long form of C4), in eight panels of post-mortem brain tissue.

Copy number of C4 structural features was measured by ddPCR; RNA expression levels were measured by RT-ddPCR. a–e, Data for tissues from the Stanley Medical Research Institute (SMRI) Array Consortium consisting of anterior cingulate cortex (a), cerebellum (b), corpus callosum (c), orbital frontal cortex (d), and parietal cortex (e). f, Data for the frontal cortex samples from the NHGRI Genes and Tissues Expression (GTEx) Project. g, h, Data for tissues from the SMRI Neuropathology Consortium (anterior cingulate cortex and cerebellum, respectively). These data were then used to inform (by linear regression) the derivation of a linear model for predicting each individual’s RNA expression of C4A and C4B as a function of the numbers of copies of AL, BL, AS, and BS. The derivation of this model, and the regression coefficients induced, are described in Supplementary Methods. In the rightmost plot of each panel, expression of C4A (per genomic copy) is normalized to expression of C4B (per genomic copy) to more specifically visualize the effect of the C4–HERV by controlling for genomic copy number and for any trans-acting influences shared by C4A and C4B; the inferred regression coefficients (Supplementary Methods) suggest that the observed effect is mostly due to increased expression of C4A.