Project Summary/Abstract Dyslexia (DYS) is a common developmental disorder with a strong genetic component which can have a significant impact on academic and vocational success as well as emotional well-being. Children with this disorder have reading scores that are at least 1 standard deviation below their age- and grade- matched peers. In spite of these diagnostic criterion, there is a great deal of heterogeneity within this label, both with regard to the severity of the core deficit(s) as well as in the genetic basis of the disorder. This heterogeneity, combined with a lack of a strong understanding of these mechanisms, leads to a one-size-fits all approach to intervention and a significant portion of individuals do not respond to the intervention option offered. Association studies in humans suggest that the dyslexia- susceptibility gene DCDC2 is associated with anatomical deficits in the brain as well as deficits on tasks that require speed. The current studies will evaluate whether this gene is causally related to these deficits by utilizing a novel knockout rat model recently developed by the PI. If it is confirmed that this gene does impact anatomy and rapid auditory processing, it would suggest that individuals with dyslexia that carry a variant in this gene may respond more effectively to interventions targeting these specific skills.

Project Narrative It is likely that individual dyslexia-susceptibility genes contribute to different deficits in dyslexia, which limits our ability to determine which children with dyslexia are best-suited for specific interventions and which children will not respond to intervention. In humans, causal studies of gene-brain-behavior relationships are not possible due to genetic heterogeneity combined with the ethical issues of manipulating gene expression. The proposed studies aim to use a novel rat model with knockout of Dcdc2 to evaluate the role of this gene on anatomical and functional deficits in dyslexia.