Łukasz J. Sznajder (Biochemistry) was awarded an NIH R16 grant ($0.75M) through the National Institute of General Medical Sciences for a project titled, "Identifying tandem repeat expansion-mediated mechanisms of autism-risk genes."
Autism spectrum disorder (ASD) is a set of neurodevelopmental conditions that affect communication and social interactions with restricted interests and repetitive behaviors.
Although ASD has one of the highest heritability rates of all complex disorders, and hundreds of genes are known to confer a risk for this condition, most ASD cases remain idiopathic. A critical barrier to progress in the field is to identify additional ASD-risk genes.
Since most of the known ASD variants are biased toward coding regions, an unmet need is to evaluate the contribution of noncoding sequences in ASD etiology, including tandem repeats (TR) that account for ~5% of the human genome.
Recently two independent large-scale genome studies uncovered previously undetected and predominantly noncoding TR mutations that have been suggested to account for ~4% of idiopathic ASD cases.
Although these studies opened uncharted territory by revealing numerous TR mutations in ASD, they were underpowered to adopt the required statistical rigor to select gene candidates for further mechanistic studies.
To overcome this critical barrier to progress in the field, we designed a framework to investigate the contribution of noncoding TR mutations in ASD etiology.
The goal of this project is to identify high-confident TR mutations in ASD. We will elucidate the molecular mechanisms induced by these mutations and demonstrate the adverse effects on their host genes. This project will profoundly impact our understanding of ASD and will inform future biomarker and therapeutic strategy development.
