Cacheiro, P. et al. Nat. Commun. 11, 655 (2020)

Data from two projects—one in man and one in mouse—are coming together to help researchers screen for disease-causing genetic variants. The result is a new classification scheme that refines the concept of ‘essentiality’ for a particular gene.

The work, dubbed Full Spectrum of Intolerance to Loss-of-function (FUSIL), combined phenotype results in mouse from the International Mouse Phenotyping Consortium with human genes dubbed by the Broad Institute’s Project Achilles as either essential or non-essential in cell lines.

Based on the cross-species data, the researches define 5 FUSIL categories with different biological properties: cellular lethal, developmental lethal, subviable, viable with phenotype, or viable with no phenotype. The authors suggest that screening against the FUSIL database could help in discovering previously unknown genetic causes of rare diseases.