In a new article published in Nature, researchers find that roughly a third of all genes in the mammalian genome are essential for life. The finding will impact our understanding of mammalian development and human disease.
The work was led by the International Mouse Phenotyping Consortium, which includes researchers from over 30 institutions worldwide.
Researchers are assessing the morphological and physiological characteristics of knockout mutations for all of the protein-coding genes in the mouse genome. The goal is to create a catalog of mouse genes that shows what each gene does.
The project aims to discover new functions for the roughly 20,000 genes shared with humans, and make all of the mouse strains available to provide a platform for dissecting the mechanisms of human disease.
In the current study, researchers reported the results of the first 1,751 genes characterized by the project. The results showed that nearly one third of the genes are essential for life.
This includes 410 lines that are fully lethal, and an additional 198 for which fewer than half of the expected number of mutants were identified.
Using a new, standardized phenotyping pipeline and mouse strains on a single C57BL/6N genetic background, the researchers established both the time of embryo death and the nature of the lethal features for these lines.
The work discovers many novel characteristics that shed light on the function of these genes.
In addition, the incorporation of high-resolution 3D imaging and automated, computational analysis of the images allowed the team to gather detailed data rapidly.
The team also showed that identification of essential genes in the mouse provides a window on human disease. This includes the discovery of a number of novel cases in which human disease genes overlap with essential genes.
Researchers suggest that the study really focuses on defining the phenotypes associated with genes that are essential to embryonic and post-natal development.
This group of genes is particularly exciting because many of these genes that are essential in mouse are also linked to diseases in humans.
The work of the consortium will contribute significantly to our understanding of the genetic bases for human diseases such as cardiovascular defects.
Citation: Dicknson ME, et al. (2016). High-throughput discovery of novel developmental phenotypes. Nature, 537: 508-514. DOI:10.1038/nature19356.
Figure legend: This Knowridge.com image is credited to National Cancer Institute.