An exploration of how we have come to understand the relationships between genes and traits, with a focus on traits of biomedical importance. We explore how physiological systems biology can be used to understand the causal pathways by which genes affect traits. Examples will be taken largely from the biomedical literature with a focus on genetic diseases and the roles of genetic background and environment in determining how (and why) genes affect traits. Readings and class participation, short papers and oral presentations on research projects. Recommended prerequisite: Biology 203L or 201L and 202L and Mathematics 112L.