Abstract A19: Exploring genetic interactions in haploid human cells

Abstract

Abstract Gene-associated phenotypes often depend on the activity of other genes resulting in genetic interactions. In model organisms, the large-scale generation of combinations of mutations has resulted in the identification of genetic interactions and provided insights into their contribution to complex phenotypes. Here we use haploid human cells combined with genome-wide mutagenesis to study genetic interactions. We have made a synthetic lethality network using query genes acting in the secretory pathway and observe that human genes frequently engage in genetic interactions. Beyond cell lethality, we search for genes, which upon loss deregulate cellular processes such as signaling pathways. Genetic modifier approaches in those mutants reveals back-up mechanisms or genetic networks contributing to the phenotype of interest. This provides a much-needed window into the robust genetic networks governing human cells. Citation Format: Vincent A. Blomen, Thijn R. Brummelkamp. Exploring genetic interactions in haploid human cells [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr A19.