Description:

Santhosh Girirajan
T. Ming Chu Professor of Biochemistry and Molecular Biology
Department of Biochemistry and Molecular Biology
Pennsylvania State University

Recent studies have suggested that genetic variants of different classes, frequency, and effect sizes individually or collectively contribute to neurodevelopmental disorders such as autism, intellectual disability, and schizophrenia. Several themes have emerged from these studies that present challenges rendering our understanding of these disorders incomplete. First, most gene discoveries for complex disorders rely on identifying individual genes with de novo (i.e., not inherited from parents) mutations. Second, the same variant or gene has been associated with nosologically distinct or comorbid clinical outcomes. Third, incomplete penetrance and variable expressivity have complicated disease prediction based on genetics and associated genetic counseling. My laboratory uses a combination of human genetics, model systems, and computational approaches to dissect the genetic architecture of complex disorders. I will present examples of our work using whole genome sequencing and quantitative phenotyping of affected families, animal models, and computational methods to provide evidence for how genetic interactions can explain the missing heritability of neurodevelopmental disorder