Neurodevelopmental and psychiatric disorders (NDDs) are characterized by impairments of personal, social, academic, or occupational functioning. There are no treatments that reverse these impairments, highlighting the need to understand their biological aetiologies. One important discovery is that genetic risk factors are associated with these disorders. Therefore, by studying these genetic factors using model systems, we can better understand how risk genes cause abnormal brain development. In the current grant, we are studying a strong genetic risk factor where individuals are missing a piece of chromosome 15 (a microdeletion) and can have autism, schizophrenia, epilepsy or developmental delay. We have assembled a research team who will use different biological model systems (mouse models, human and mouse brain imaging, cultured human brain cells, genetic sequencing and bioinformatics) to study the chromosome 15 microdeletion. Because each model system has advantages and disadvantages, our combinatorial approach will have synergy and serve as a powerful method to understand how this genetic deletion causes NDDs. Our approach will also shed light on the factors that contribute to the different clinical symptoms associated with this syndrome. This will lead to better disease classification, closer monitoring of patient symptoms depending on their genetic diagnosis, and possibly early invention. Our preliminary results demonstrate the success of using a multidisciplinary approach. We have discovered a novel target gene in this deletion that is responsible for most of the neurodevelopmental brain abnormalities in our mouse model. Our team has the appropriate scientific and clinical experience to generate new information that will help clinicians manage patients with a chromosome 15 microdeletion. Our approach will not only be successful for this microdeletion, but will serve as a model to study other, similar, poorly characterized genetic lesions.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
