Networks of Genes, Epistasis and a Functionally-Clustered Genome
Caleb Webber
Programme Leader, Neurological Disease Genomics, MRC Functional Genomics Unit, Department of
Physiology, Anatomy & Genetics, Oxford University, UK
Autism is highly genotypically heterogenous disorder, to which variants in a large number of genes likely
to contribute. Identifying the molecular pathways in which these genes act provides not only insight into
the pathoetiology but also translational routes to diagnosis, patient stratification and targeted therapy. By
combining the strengths of many different types of functional genomics data, we create sensitive
functional networks that identify commonly perturbed molecular networks underlying genetic disorders.
For autism, these approaches unify different classes of genetic risk variants, identify multiple distinct
molecular aetiologies, and also identify the contribution of genetic interactions, which is one of the most
significant challenges facing human disease genetics. Finally, these approaches suggest that the
disruption of genomically-clustered functionally-related genes is a significant and common characteristic of
large pathogenic structural variants.