Periodic Reporting for period 1 - 7DUP (Characterization of 7q11.23 reciprocal aneusomy syndromes: from patients to functional pathways (and back))
Reporting period: 2016-04-01 to 2018-03-31
To better understand the pathophysiological mechanisms disrupted in patients carrying 7q11.23 alterations, we proposed a combined experimental and systems biology analytical approach with the following specific aims: (1) Identify and characterize patients with 7q11.23 CNVs; (2) Create reciprocal genetic models of 7q11.23 CNVs by generating induced pluripotent stem cells derived from patients and identify transcriptional alterations in differentiated neural precursors and mature neurons; and (3) Identify key functional pathways commonly and/or symmetrically disturbed across patient-specific neurons of 7q11.23 CNVs.
In the second aim of this project, we have created reciprocal genetic models of 7q11.23 copy number variants by generating patient-derived induced Pluripotent Stem Cells (iPSC) that were differentiated to neural precursors and differentiated neurons. We then studied the changes in the transcriptome of these in vitro models of brain to investigate the genes that are altered by these alterations at 7q11.23.
Finally, we used a Systems Biology approach integrating multiple sources of biological evidence to identify genes deregulated and pathways altered in these disorders. We identified multiple genes differentially expressed in specific types of neurons that warrant further investigation.