Talk title: Minding our P’s and Q’s: Questions in human genetics about a CNV region and brain-based traits

Date: Wednesday, November 10, 2021
Speaker: Lauren Weiss, Ph.D.
Professor, Department of Psychiatry, University of California San Francisco

Host: Dr. Mriganka Sur

Abstract: Deletions and duplications of the multigenic 16p11.2 and 22q11.2 copy number variant (CNV) regions are associated with brain-based disorders including schizophrenia, intellectual disability, obesity, bipolar disorder, and autism spectrum disorder (ASD).  Hypothesizing that DNA copy number exerts most effects via impacts on RNA expression, we attempted a novel in silico fine-mapping approach utilizing non-CNV carriers as well as gene expression, GWAS, and biobank data to begin answering some big genetic Qs.  Positional cloning: which individual genes in the region contribute to CNV-associated phenotypes?  Pleiotropy: is the same CNV gene responsible for association with multiple brain-based traits? Penetrance/Expressivity: are these CNV genes contributing to other unrecognized health implications for carriers?  subtler related phenotypes in non-carriers?  Polygenicity/Epistasis: do multiple genes in a region contribute to the same trait?  Prediction/Prevention/Pharmaceuticals: can insight from these investigations give us more information on both CNV and ‘idiopathic’ trait genetics for future personalized medical approaches?