ICNC Abstracts, ICNC 2018

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Combining Pathway analysis and animal model behavioral testing for the identification of treatment for neurodevelopmental disorders
Francois Bolduc, Richard He, Kerri Whitlock, Cory Rosenfelt

Last modified: 2018-09-09

Abstract


Our understanding of the genetic basis of neurodevelopmental disorders (NDD), such as intellectual disability (ID) and autism spectrum disorder (ASD), has exploded with the advent of chromosomal microarray and next-generation sequencing. Combined efforts have identified over 1500 genes associated with NDD. Nonetheless, this complexity and the view of NDD as fixed in development has increased the gap between diagnosis and treatment. Using a genome wide pathway analysis approach, we aimed to define networks of genes involved in NDD with conserved function. Interestingly, we identified 10 major pathways with high concentrations of NDD genes. Importantly, we observed that some networks were linked with well-established genes involved in cognition and memory formation such as CREB and BDNF. We also observed that other genes formed networks more involved in cellular development functions. Next, we took advantage of memory and social interaction models in Drosophilato gain a better understanding of the role of those genes in sensory processing, memory, and behavior response to stress. We identified several genes with prominent sensory processing and memory defects. In addition, we found that despite the lack of acute post-natal role of genes, pharmacological intervention could still improve behavioral defects, an important paradigm change. Together, our results underscore the need for bioinformatics gene pathway analysis in developing rational targeted candidate drug testing based on networks. This mechanistic therapeutic approach will maximize the impact of treatment by enhancing screening in pre-clinical models and making translation to human patients more successful.

Keywords


neurodevelopment; genomics; pathway analysis

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