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Genetics of Down Syndrome

Large-scale genetic investigation of
Down syndrome neural deficits.

Down syndrome (DS) is the most prevalent genetic cause of intellectual disability, yet many of the genes implicated in DS are poorly understood or even unstudied. Genetically tractable and easily observable larval zebrafish provide an ideal platform for studying the large number of genes associated with DS and finding possible treatments. There are over 150 protein-coding genes on the trisomic Hsa21, and it is unclear which genes contribute to the neurodevelopmental changes observed in DS. We are overexpressing these genes to determine their impact with our highly sensitive brain activity mapping approach. The genetic tractability of zebrafish will also allow us to co-express pairs of genes to unravel complex genetic interactions. Ultimately, we will define targets and phenotypes for therapeutic screening strategies.