Genetic Disorders


Medical genetics faces two major challenges. First, we still fail to identify causal mutations for the majority of patients affected by a genetic disorder. Second, even when the causal mutation is identified, we frequently have little or no understanding of the molecular pathways that are affected by the mutation and cause the disease phenotype. ‘Omics profiling of samples from affected patients promises to help on both fronts. It is able to indicate which mutations have physiological effects by assessing whether their corresponding molecular pathways are affected. Moreover, it can help expanding the set of possible targets for molecular intervention by revealing the causal chain of intermediate molecules (RNAs, proteins, metabolites) through which a genetic variant affects a physiological phenotype [Gagneur, PLoS Genetics 2013]. The objective of this work package is to provide the computational methods needed to fulfil this promise. Specifically, we will deliver methods for the identification of most likely causal genetic mutations and affected pathways of mitochondrial disorders. We will put a particular focus on using metabolic and transcriptomic data and their interrelationships, which are so far not well understood.

Participating partners

  • Technische Universität München (Lead Partner)
  • Roswell Park Cancer Comprehensive Center, Buffalo
  • ETH Zurich
  • Instituto de Engenharia Mecânica, Lisbon
  • Technische Universität München, Klinikum Rechts der Isar