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Penn Bioinformatics Forum – Kelly Frazer, PhD
March 12 @ 8:00 am - 5:00 pm
Kelly Frazer, PhD
Professor of Pediatrics
Division Chief, Genome Information Sciences
Director, Institute for Genomic Medicine
University of California, San Diego
Using iPS cells and derived cell types to functionally annotate human genetic variants
Over the past six years, Dr. Frazer’s lab has systematically derived and characterized a unique collection of iPSC lines from 222 individuals – referred to as iPSCORE (iPSC Collection for Omic Research). iPSCORE is currently being used to analyze genotype – molecular phenotype associations in both iPSCs and iPSC-derived cardiomyoctyes (iPSC-CMs) from over 135 individuals. We are in the process of analyzing how regulatory variants influence the expression of cardiac molecular phenotypes including RNA expression (RNA-seq assays), chromatin states (ATAC-seq and H3K27ac ChIP-seq assays) and chromatin loop formation. Comparing the iPSC-CM transcriptomes and epigenomes to GTEx and Roadmap showed that they have expression profiles similar to fetal cardiac tissue. We have leveraged these expression data in combination with whole-genome sequences to perform an expression quantitative trait loci (eQTL) study, resulting in the discovery of developmental stage (fetal) specific regulatory variants that are associated with cardiac disease. These results show that analysis of iPSC-CMs identifies cardiac disease regulatory variants that are active in the fetal heart, but not in adult heart tissues, indicating that they play a role in development.