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

• Child and Adolescent Psychiatry
• Clinical Trials
• Neuropsychiatry
• Psychiatry

The Autism and Related Disorders Research Group (Group Head: Prof. Louise Gallagher) is an interdisciplinary group of research scientists and clinicians with expertise in molecular and statistical genetics, neuroimaging (MRI) and behavioural phenotyping. The group is engaged in research oriented towards better understanding the causes of autistic spectrum disorders (ASD) and other related neurodevelopmental disorders to provide improved diagnostic methods and treatments/ interventions. Key activities of the group include investigation of rare and common genetic variation in autism, the interplay between genetics and the behavioral/ neurocognitive characteristics of autism and related disorders and understanding functional and structural brain connectivity. In house research projects are well integrated with the activities of a range of research collaborations including the Psychiatric Genetics Consortium (PGC) Autism Genome Project (AGP), MSSNG, the UK10K sequencing program, The Autism Brain Imaging Data Exchange (ABIDE). The group is affiliated with the Neuropsychiatric Genetics Research Group and the Trinity College Institute of Neuroscience and has access to wet and dry lab space, 3T MRI scanner and Electrophysiology suite. The group has expertise in molecular genetics analyses, functional and structural neuroimaging analyses and expert behavioural phenotyping and neurocognitive testing.

Neurexins are neuronal adhesion molecules on axon terminals, which bind postsynaptic Neuroligins (encoded by NLGN). They are particularly implicated in excitatory neurotransmission and therefore could underpin excitation/ inhibition imbalance as a mechanism for causing neurodevelopmental disorders. NRXN1? is a rare but significant risk factor for ASD, schizophrenia, mental retardation and bipolar disorder. Copy number variants (CNV) are frequently found in NRXN1 and are thought to be causative, however the phenotypic expression is highly variable, and occasionally NRXN1 deletions are found in unaffected carriers. Pleiotropy, or apparently different effects caused by the same gene may explain variable phenotype expression. However other possible explanations may be a second genetic mutation in the genome or differential post transcriptional regulation of gene expression. My group has previously ascertained a cohort of patients carrying NRXN1 deletions (n=24) and their family members who are unaffected. There are a range of neurodevelopmental outcomes associated with the deletions in these individuals. These have been extensively characterised phenotypically and have undergone MRI and EEG neuroimaging. Additionally induced pluripotent stem cells (iPSCs) have been established in a collaborators lab to derive neuronal cell models for phenotyping and functional studies. Now the aim is to identify if other factors impacting directly or indirectly on gene function might influence the clinical presentation in these patients. This project will focus on whole genome sequencing and RNA sequencing and analysis in NRXN1 carriers to determine if there are other potentially deleterious mutations or differences in gene regulation that may explain the observed phenotypes. The project offers the opportunity to develop skills in handling and annotating sequencing data, developing bioinformatics skills and to analyse sequencing data together with clinical and neurocognitive/ imaging phenotypes. Opportunity also exist for training visits to collaborator labs to acquire skills and further develop collaborations.