PgmNr D82: Modelling Intellectual Disability Disorders in Drosophila - from Genes to Functional Modules and Clinical Applications.

Authors:
Annette Schenck; & laboratory


Institutes
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, the Netherlands.


Abstract:

Intellectual Disability (ID) disorders are, due to their high frequency and lifetime long expenses, the biggest unmet challenge in clinical genetics and among the largest cost factors of health care in Western countries. ID disorders are largely monogenic, and disease gene identification over the past decade has been highly successful. More than 800 causative genes (‘ID genes’) have been reported, providing unique stepping stones into the molecular basis of cognition. However, the role of most ID genes, particularly in the nervous system, is poorly understood. A highly efficient model organism is needed to make use of the available information and advance our knowledge in this field.

I will present a synopsis of our work in humans and Drosophila, which aims to identify novel pathways and mechanisms that are commonly disrupted in ID and clinically & genetically overlapping Autism Spectrum Disorders. Large-scale phenotyping in Drosophila revealed novel roles of ID genes, such as regulation of basal neurotransmission, synapse development and learning. Our data present experimental evidence that ID disorders converge on highly connected, evolutionarily conserved functional modules. Consistent with conserved modularity, Drosophila phenotype groups mirror human disease similarity, establishing Drosophila as a model for human phenomics. I would also like to discuss how Drosophila can contribute to disease gene validation in the era of Next Generation Sequencing, and report on our ongoing effort to establish parallel outcome measures in human patients and Drosophila models to enhance the translational impact of our model.

Our goal is to provide conceptual advance in understanding of higher brain function in health and disease and to significantly contribute to the development of 'Next Generation' diagnostic and therapeutic strategies for ID and related disorders.