UC San Diego

Our improved understanding of cellular biology, and, in a larger sense, human variability, relies on the accurate identification and analysis of disease-causing variants. Through the study of natural and artificial genetic damage, we’ve helped identify gene function, compile protein interaction networks and, reclassify human diseases by their underlying biology. Such discoveries have allowed the repurposing of treatments based on improved understanding of underlying mechanism and increased the adoption of genetic screening, both of which have made great headway in decreasing the human suffering caused by genetic disease.

Despite working in the simplest constructs of genetic disease, with established expectations of inheritance and complete penetrance, the identification of causal mutations remains challenging. This is due in no small part due to incomplete assessment of human genetic diversity. The human genome has been found to have a high background burden of predicted damaging variation and a propensity for rare variation to remain population specific. Here we demonstrate multiple contributions to the field. We built a series of pipelines tasked with the through analysis of exome data for purpose of identification of disease variants, analyzed the genetic structure of the Greater Middle East to aid in future genetic-studies in these regions, and approach open genetics questions including the role of genetic purging in the background distribution of disease-causing variants.