Autism (ASD) Genetics to Mechanism
We have brought together genome wide associate data sets (GWAS) and ClinVar analysis of genes tied to autism development highlighting lack of mechanistic knowledge of the system and an overwhelming number of Variants of Uncertain Significance (VUS).
Using Computational tools to identifying functional regions on ASD associated genes
Using our computer strategies we have take multiple genes involved in autism and developed deep codon usage evolutionary information for each.
Detailing ASD VUS
Then we take a deep dive into all known ClinVar variants for the gene, identifying VUS that are likely functional and developing a working hypothesis for variant mechanism that can be tested.
Neural Organoids and mixed neural cultures
To test the role of genes we use neural progenitor cells (NPCs) and iPSCs that we can manipulate with CRISPR/Cas9 technology followed by differentiation to brain organoids or mixed neural cultures.
Studying the transcriptional control of male elevated ASD risk
Finally, we study the complex synergistic regulation of the male specific gene, SRY, and the Androgen Receptor, AR, that regulate male specific transcriptional regulation.