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Developmental Genetics

Global study leads to discovery of genes relevant for development in mice and humans

A third of all genes in the mammalian genome are important for survival, and many of the essential genes found here also play a key role in human diseases. Working with colleagues from the International Mouse Phenotyping Consortium (IMPC) and INFRAFRONTIER, scientists from the Helmholtz Zentrum München (HMGU) describe the large-scale discovery of those genes and how it will impact understanding of mammalian development and human disease. The results were recently published in the Nature magazine.

Prof. Dr. Hrabě de Angelis, Source: HMGU

The characterization of the first 1751 genes analysed by the IMPC led to the discovery of 410 genes whose genetic deactivation in the mouse impaired the development of embryos so strongly that they were not viable. Mutations in a further 198 genes led to fewer offspring. The genetically modified embryos were examined by a new method which included recording 3D images at a number of different times and running a computer analysis of the acquired data. The expressions of new genes were also characterized and new phenotypes were found for lethal genes already known.

The group also showed that identification of essential genes in the mouse provides a window on human disease, including the discovery of a number of novel cases where human disease genes overlap with essential genes. In addition, in collaboration with the ExAC Consortium (Lek et al., Nature 536, 2016), they showed that human orthologs of mouse essential genes are significantly depleted for loss-of-function mutations in humans, and that these genes are thus strong candidates for undiagnosed human genetic conditions.

"Our study broke new ground, and not only in the field of embryology. The findings are also particularly interesting with respect to new treatment strategies. The new knowledge regarding genes essential to life and their signal cascades will be very important in the development of new treatment methods for human diseases where they will help make it possible to exclude undesirable effects already during the planning stage," says the project co-initiator and director of the German Mouse Clinic, Prof. Dr. Martin Hrăbe de Angelis from the Helmholtz Zentrum München and the TU Munich.

For the scientific community, one important contribution is the provision of all acquired data through the IMPC web portal ( This allows scientists from all over the world to use the results of this study for further interesting research projects.

Further information:

Original-Publikaiton: Maja Bućan & Stephen A. Murray et al.: High-throughput discovery of novel developmental phenotypes; Nature, DOI:10.1038/nature19356

Link to publication

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.

The German Mouse Clinic in theInstitute of Experimental Genetics at the Helmholtz Zentrum München is a member of the International Mouse Phenotyping Consortium (with a total of 18 research units; Its objective is to work with its partners to investigate the functions of all protein-coding genes in the mouse genome. The Consortium is particularly interested in studying the 20,000 genes shared by humans and mice in order to provide a platform for research into the mechanisms behind human diseases.

INFRAFRONTIER is the European research infrastructure for the development, phenotyping, archiving and distribution of mammalian models. It gives researchers around the world centralized access to extensive resources that are provided by top European research centers in fifteen European countries. INFRAFRONTIER is consequently laying the foundation for research into the genetic causes of human diseases.