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• genetics, genomics and molecular biology
• neuroscience and mental health

• Paediatrics

• Neurology
• Psychiatry

The Mitchell lab is interested in the genetics of neural development and of neurodevelopmental disorders. We study these processes using experimental genetic approaches in mice and genetic analyses in humans. We have identified and characterised numerous genes in the mouse that are involved in controlling neuronal cell migration, axonal guidance and synaptic specificity during brain development. Defects in these processes can lead to neurological disturbances, such as seizures, as well as behavioural phenotypes of relevance to psychiatric disorders. We are currently using statistical methods to dissect the genetic architecture of schizophrenia, analysing large-scale genetically characterised samples. Future work will involve genome-sequencing studies of patients with paediatric epilepsies, cortical malformations or unexplained developmental delay. We aim to identify new disorders of cortical development and model them in mice to elucidate pathogenic mechanisms.

The Genetics of Neurodevelopmental Disorders (Edited by Kevin J. Mitchell)
www.wiley.com/buy/9781118524886

Dissecting the genetics of disorders of cortical development

Disorders of cortical development are an important cause of childhood epilepsies, developmental delay, intellectual disability and psychiatric and behavioural problems. Many cases have a genetic etiology but for most the specific genetic cause is unknown. New genome sequencing technologies offer the means to identify pathogenic mutations in many more cases. This project will aim sequence the whole genomes of several hundred pediatric cases of suspected disorders of cortical development, along with their parents. The genome sequences will be surveyed for rare, inherited or de novo mutations in evolutionarily constrained genes with possible roles in neural development. Candidate pathogenic mutations will be surveyed in global databases to assess allelic frequency and identify additional cases of rare disorders. We will follow up discoveries in humans by recapitulating a subset of candidate mutations in mice using CRISPR-Cas9 genome editing and testing for effects on neural development. We aim through this program of research to define new genetic disorders of cortical development and further identify biological processes underpinning development of the human brain.