Dissection of the AnkyrinG interactome.

While the introduction of next generation sequencing led to a breakthrough in the discovery of novel genes responsible for neurodevelopmental disorders, most notably intellectual disability and autism, our understanding of the underlying disease causing pathology is lagging behind, in part due to the extreme genetic heterogeneity. Despite substantial in silico evidence that many diseases genes responsible for neurodevelopmental disorders cluster in a relatively limited number of protein protein interaction (PPI) networks, no experimental work on the subtle phenotypical effects that disturbances of such a network may cause has been reported to our knowledge. In this application, we therefore zoom in for the first time on the effects of the combined genetic variation present in an entire PPI network, rather than on the effect of mutations in single genes. We selected the AnkyrinG interactome, as it is a well-defined interaction network that is strongly connected with multiple neurodevelopmental disorders. By a detailed characterization of the genetic variation present in the AnkyrinG interactome in a large patient cohort, in combination with transcriptomics, proteomics and validation studies, we want to define the role of this PPI network as a unifying factor in neurodevelopmental disorders.

Keywords:AUTISM

Disciplines:Genetics, Systems biology, Molecular and cell biology