There are at least three hypotheses to explain how 22q11.2 haploinsufficency could cause the cognitive and psychiatric phenotypes of SZ: i. unmasking recessive alleles in the deleted region, ii. a major effect of a single dosage-sensitive gene, and iii. under-expression of several dosage-sensitive genes [106]. Existing data from animal models and systematic genetic association studies seem to support the under-expression model [8, 107]. The co-expression networks for our DEGs also support this hypothesis, as a small number of DEGs accounted for the majority of the connections in the networks (Additional file 10) and moreover only a few of the 22q11.2 genes were among the highly connected genes (Table 3). In addition, the most connected genes varied from brain regions and developmental stages. In general, CDC45 had the largest number of connections in the embryonic stage while PRODH was among the five most connected genes in the adolescence brain regions (Table 3). Note that the ranks of DEGs according to their numbers of connections in the co-expression networks exhibited better correlations in brain regions of the same developmental stage (Table 4).
