Smith, D. J.

The only comprehensive genetic interaction map of the human genome was constructed using increased gene copy number in radiation hybrid (RH) cells. More recently, interactions restricted to essential genes were identified using loss-of-function alleles made by CRISPRi technology. I compared the two maps to understand their similarities and differences. Both maps overlapped significantly with a database of protein-protein interactions. However, interactions in the RH and CRISPRi datasets had no significant overlap, even though the participating genes overlapped significantly. In addition, the RH map showed highly significant similarity with an interaction map constructed from genome-wide association studies (GWASs), while the CRISPRi map did not. This study reveals that gain- and loss-of-function alleles highlight different aspects of the genetic interaction landscape.