Linking Genotype to Clinical Phenotypes of Ciliopathy Patients – PHRT


Linking Genotype to Clinical Phenotypes of Ciliopathy Patients

Short Summary

This project aims to better understand how DNA mutations are linked to specific clinical features of patients with so-called “ciliopathy” disorders, caused by dysfunction the cells’ antenna which senses signals from the cellular environment. For this, we will develop computational methods that can predict the impacts of gene mutations at the protein level and combine these with experimental methods where such disease causing mutations can be studied in the lab. In the future, these approaches may lead to improved genetic-based prediction of clinical outcome for patients and potential novel treatment options.


The aim of this project is to improve our predictive ability for ciliopathies by harnessing the wealth of data available through efforts of the scientific community over the past two decades. We will use computational approaches to predict the molecular and cellular consequences of disease-causing mutations as well as the clinical features of the patients carrying such mutations. Results will then be tested in cellular models where specific mutations can be introduced and the impact of these mutations can be tested in the lab.


The computational and experimental methods developed in this proposal may, in the future, improve genetic based diagnosis of patients and facilitate the development of novel patient specific treatment options.


Over the past two decades, the field of Genetics has witnessed a fantastic revolution driven by continuous technological breakthroughs. Since the completion of the human genome project, these technologies have allowed us to “read” any human genome in a short time and at reasonable cost. Nevertheless, we are still facing major challenges in the interpretation of the acquired sequences. As a result, predicting phenotype (the clinical features) based on genotype (the genetic changes) remains a major challenge. This is particularly well illustrated in a group of human disorders called ciliopathies, which are caused by dysfunction of a cellular organelle – the primary cilium – required for sensing signals from the cellular environment. Cilia are present on most cells of our bodies and their dysfunction can therefore cause symptoms in most organs. Typical clinical features seen in ciliopathies are central nervous system malformations or dysfunction, leading to intellectual disability and neurological symptoms, retinal degeneration, fibro-cystic renal or hepatic disease, endocrinological disturbances and skeletal problems. Over 35 ciliopathies have been described, with ~200 associated genes, where dysfunction of most of these genes can cause a wide range of distinct clinical features within the ciliopathy spectrum. Given this prominent variability, we cannot predict to date which of the ciliopathy-associated clinical features will occur in a given individual based on their genetic change. This substantially complicates medical management, for example in a prenatal setting or to determine who requires surveillance measures and early intervention for progressive features such as retinal degeneration or kidney disease.


Prof. Dr. Pedro Beltrao

ETH Zurich


  • Prof. Dr. med. Ruxandra Bachmann-Gagescu, UZH, Institute of Medical Genetics and Department of Molecular Life Sciences


In Progress

Funded by