Investigating the dysregulation of gene expression in 22q11.2 deletion syndrome with human IPS and ES cells and its link to schizophrenia (360G-Wellcome-102428_Z_13_A)

We hypothesise that 22q11.2 deletion syndrome (22q11.2DS) has an increased risk to schizophrenia and Parkinsons disease (PD) due to abnormal dopaminergic(DA) neuronal development and/or function, which is the consequence of a global dysregulation of gene expression triggered by the haploinsufficiency ofDGCR8. We will perform a comprehensive analysis of the phenotypes of DA and MSN neurons derived from 22q11.2DS induced pluripotent stem cells (iPSC), DGCR8 knock-out human embryonic stem cells (ESC), and if time permit, 22q11.2DS iPSCs overexpressing transgenic DGCR8. Moreover, we will seek further support that DGCR8 has a primary role in 22q11.2DS by analysing the dopaminergic neuron system of DGCR8 conditional knockout mice. This will provide us a unique understanding of the abnormalities caused by thedeletion and by cross-referencing our results and previous genomic studies this study will provide valuable insight to how these deficits may confer riskto schizophrenia and PD.