About one-third of 1,751 genes are essential to life, according to the first comprehensive survey of the mouse genome, which aims to provide tools for studying human diseases.
Mutations of these genes cause death at the embryo stage. Many of them have counterparts in the human genome, so understanding why these genes are so vital could help prioritise human genes for study.
"This is the first comprehensive survey of its kind, and it shows that one-third of the mouse protein-coding genome is essential to life," said Kent Lloyd, professor at University of California, Davis (UC Davis).
"This begins to inform what may be happening in people," said Lloyd, who is the director of the Mouse Biology Programme at UC Davis.
The International Mouse Phenotyping Consortium is generating and characterising "knockout" mutations for all of the protein-coding genes in the mouse genome.
The consortium aims to discover new functions for the roughly 20,000 genes mice share with humans, providing tools for investigating human disease.
The study reports the results of the first 1,751 genes characterised by the consortium, finding that nearly one-third are essential for life.
These include 410 that are fully lethal when mutated, and an additional 198 for which fewer than half of the expected number of mutants were identified, meaning that only a few variations of the gene lead to viable offspring.
Using high-resolution 3D imaging and automated, computational analysis of the images, researchers established for each gene both the time of embryonic death and why the embryos died, shedding light on the function of these genes.
Many of these genes have counterparts in the human genome, and these genes are thus strong candidates for undiagnosed human genetic conditions.
"Where we don't know the cause of disease, they may not have a full knockout, but a variant that doesn't work quite right," Lloyd said.
The mouse data could help prioritise genes to study through the national Precision Medicine Initiative, he said.
The knockout mice generated are available to other researchers who may be investigating particular pathways or disease phenotypes.
The research appears in the journal Nature.
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