Understanding complex genetics – how do our genes affect our behavior and development?

Most human diseases and biological traits, such as autism and lifespan, have a strong genetic, or heritable, component.  However, current techniques have failed to identify the majority of the genes responsible for heritability. The genetic architecture controlling most biological traits is incredibly complex – hundreds of interacting genes and variants combine in unknown ways to create phenotype. The McGrath lab is interested in developing approaches to understand in greater detail how complex biological traits are controlled by our genes. This work should improve our ability to identify genetic risk factors in humans and understand their complex interactions to predict disease risk or a biological trait. We are taking two approaches to address this question, using neural circuits in the small nematode C. elegans as a model. We are harnessing directed evolution experiments to understand how genetic changes affect development, reproduction, and lifespan. Due to the evolved strains low level of genetic diversity, we can rapidly identify the genetic changes responsible for changes to these traits. We are also mechanistically studying how these genetic changes modify the neurons and cells that control biological traits. We believe this work will lead to insights into evolution, multigenic disease, and systems biology.