At the embryonic stage, CDC45, one of the five deleted genes known to modulate the cell cycle (the other four are RANBP1, HTF9C, HIRA and UFD1L, as noted above), showed the greatest connectivity with other DEGs, indicating that it may be the most impacted process. Analysis of such highly connected DEGs and the non-differentially expressed genes with high co-expression with the DEGs uncovered functional clusters involved in cell cycle, cell differentiation and cell growth. These results suggest that genes in these functional clusters may be co-regulated, and reduced dosages of 22q11.2 genes may disrupt the co-regulation relationship, compromising mitotic cell cycle regulation and neurogenesis in early embryonic brain development. Interesting, many of the 22q11.2 genes, including CDC45, are expressed at the highest level during mid to late gestation - the peak timing of neurogenesis - and then decrease substantially thereafter (Additional file 12) [71, 129], in support of their potential importance in early neurodevelopment.
