Researchers from the Dept. of Human Genetics, together with colleagues from Leeds, London, Seattle, and about 40 other institutions worldwide, have uncovered the most comprehensive list yet of genes implicated in a group of common inherited diseases, the ciliopathies. The research, published in Nature Cell Biology, means that these disorders can be diagnosed more quickly and could lead to new treatments for patients.
Ciliopathies are caused by defects in cilia, finger-like projections from the cell’s surface that act as microscopic “antenna” for reception of signals outside of the cell, such as light in the retina or fluid flow in the kidneys. Cilia also transmit these signals to the corresponding processes of the cell, allowing a proper and rapid response. Disrupted cilia development or function due to genetic defects can result in a range of disorders called ciliopathies. Around 1 in 1000 people suffer from a ciliopathy. Common complications of ciliopathies are kidney failure, a significant cause of childhood disease and death, hearing loss, blindness, skeletal abnormalities, and even cancer.
Miriam Schmidts, who recently joined the Human Genetics department as a Hypatia tenure track fellow coming from London, and the group of Ronald Roepman, recently appointed professor of ‘Molecular Biology of Ciliopathies’ at Radboud University, were major contributors to the current resource article in Nature Cell Biology. They publish the results of a ‘whole genome siRNA screening approach’ to knock down every gene in the genome and evaluate the involvement in cilium formation. Through this ‘blind’ approach, the researchers were able to detect many new and unexpected processes that ensure the proper functioning of cilia. In principle, each of these processes could be involved in a ciliopathy, which they confirmed for two new genes for Jeune syndrome and Joubert syndrome. Graduate student Minh Nguyen (photo up) from the Roepman group then was able to determine a functional ciiliopathy module in which the defective protein associated with Jeune syndrome, C21orf2, was also active.
The research is important for a better and quicker diagnosis of these mostly very severe disorders, and could lead to new treatments for patients. It was largely funded by the EU FP7 project ‘SYSCILIA’, coordinated by Roepman.
An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. Nature Cell Biol 2015.
On the 30th of November and the 1st of December 2015, the Radboud Institute for Molecular Life Sciences organizes an international meeting on cilia entitled New Frontiers in Cilia Medicine.
Ronald Roepman Miriam Schmidts
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