This is the first study of gene expression profiles in early differentiating neurons derived from patient-specific iPSCs that were generated from SZ and SAD patients with 22q11.2 deletion. Our transcriptomic analysis provides insight into the neuronal functional disruptions of 22q11.2 deletion. We show that 22q11.2 haploinsufficiency at the genetic level is recapitulated in RNA expression of in vitro neurons. At the molecular genetic level, GO and canonical pathway analyses of the differentially expressed genes implicate the potential disruptions of MAPK signaling, cell cycle and apoptosis in 22q11.2 SZ neurons. At the network level, we find that 22q11.2 genes and their co-expressed targets likely play two distinct roles during brain development, with a CDC45 mediated cell cycle pathway involved in embryonic brain development and a PRODH modulated subnetwork contributing to adolescent brain functions. We also uncovered a potential interchromosomal interaction between 22q11.2 and 6p21, suggesting a molecular link between immune deficiency and additional disruption of synaptogenesis in 22q11.2 DS mediated by the non-immune function of HLA proteins on this process.
