Caleb Webber PhD
|PA||Unit Administrative Officer: Emily Frape|
|Fax (PA)||01865 282690|
|Contact address||MRC Functional Genomics Unit, Department of Physiology Anatomy & Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, United Kingdom|
Dr Caleb Webber
My group is gaining insights in to complex neurodevelopmental and neuropsychiatric disorders using functional and integrative genomics. We exploit recent large-scale genetic data sets to identify significant molecular features that can help identify which genes contribute to these complex disorders.
We focus on rare, dispersed, genetic mutations that each may be observed in only a few individuals. To do this, we must first have a clear understanding of how and where mutations arise in the human genome. In this respect, we have contributed significantly to the understanding of structural variation within the human population (see Webber et al., Nguyen et al. and Mills et al.) identifying distinct regions of the human genome that are prone to particular mutational and selectional biases.
In order to identify genes whose variants contribute to genetic disease, we exploit large genomics datasets that describe the genomes of hundreds, sometimes thousands, of individuals. Through novel methodologies, we discover statistically-significant functional differences that distinguish the mutations observed in the patient cohort from those observed in an appropriate control cohort. The functional characteristics that differentiate case mutations from control mutations yield insights in to the pathogenic mechanisms underlying the disorder and propose novel, experimentally-tractable hypotheses.
In particular, we have applied the phenotypic-associations made by disrupting genes in the mouse (“mouse knockouts”) as a novel large-scale functional genomics resource. In a proof-of-concept publication, we showed how significant biases could be detected among the set of mouse phenotypes associated with those human genes affected by mutations in patients with intellectual disability (Webber et al). We are now extending this approach using integrative genomics to incorporate annotations from gene expression, protein-protein interactions and other resources thereby creating functional linkage networks of relevance to particular disorders.
Although our approaches are applicable generally to human genetic disease, we are particularly interested in neurodevelopmental disorders, such as intellectual disability, developmental delay, autism and ADHD, along with neuropsychiatric disorders such as biopolar disorder and schizophrenia. The group is a major contributor to the FP7-funded GENCODYS (Genetic and Epigenetic Networks in Cognitive Dysfunction) project (http://www.gencodys.eu/). Our research is collaborative by nature and we welcome inquiries.
See the Group Website for profiles of group members.
- Jiannis Ragoussis , Wellcome Trust Centre for Huamn Genetics, Oxford
- GENCODYS consortium
- Joris Veltman , University Medical Center Nijmegen
- Jayne Hehir-Kwa , University Medical Center Nijmegen
- Tamim Shaikh , University of Colorado
- Stephen Scherer , Centre for Applied Genomics, The Hospital for Sick Children, University of Toronto