Understanding the genetic basis of complex neurodevelopment disorders
A fundamental aim of human genetics is to understand the genetic factors that underlie disease risk. While as a field we have been extremely successful in identifying the genetic basis for roughly half of all Mendelian disorders, more common and genetically complex diseases are proving much more challenging. It is likely that low frequency, rare, and de novo variants explain at least part of the so-called missing heritability of common diseases.In only the past several years, technology used to selectively sequence the protein-coding portion of the genome (i.e., the “exome”) has had a transformative effect on our ability to discover rare, nonsynonymous variation in human genomes. However, there are still numerous challenges to interpreting this data in the context of both rare and common diseases: specifically, 1) Locus heterogeneity, 2) Discovery of cryptic genetic variation, and 3) Interpreting the functional consequences of individual mutations.
Highlights of my past research successes include: developing a chromosomal outlier approach to identify candidate genes for Tourette’s syndrome and autism, pioneering trio-based exome sequencing in simplex autism, and developing new technologies for rapid and economical targeted resequencing. I plan to build on this experience by forming a strong and diverse research group focused on developing and implementing cutting-edge methods and technologies for discovery and replication, molecular diagnosis, functional dissection of pathways, and targeted therapeutics for neurodevelopmental and related disorders. This work has the potential to dramatically improve the lives of individuals affected with these currently untreatable disorders through early intervention and biologically based personal therapies.