Unravelling the full spectrum of pathogenic variation using Saturation Genome Editing

Our incomplete understanding of how rare genetic variants contribute to disease phenotypes substantially limits the clinical utility of genomic data. To address this challenge, we developed Saturation Genome Editing (SGE), a CRISPR-based method to assay all possible single nucleotide variants across targeted genomic regions. We’ve used SGE to functionally characterise over 10,000 variants across tumour suppressor genes such as BRCA1 and VHL. The resulting variant effect maps reveal loss-of-function variants acting via diverse mechanisms and predict human disease risk with high accuracy. Ongoing work in the Findlay lab involves scaling SGE and related genomic technologies to more cell types, assays, and genes, towards the ultimate goal of being able to predict the phenotypic consequences of any human variant.

Dr. Greg Findlay is the group leader of the Francis Crick Institute’s Genome Function Laboratory. He received his bachelor’s degree in Biology from Carleton College before completing MD/PhD training at the University of Washington in Seattle. Working with Dr. Jay Shendure, Greg led the development of new genomics techniques, including Saturation Genome Editing, GESTALT, and ScanDel. Greg started his independent group at the Crick in autumn of 2020, where his lab develops and employs high-throughput methods for characterising human genetic variation.