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Abstract

The past decade of genetics research has been defined by the discovery of the profound effects non-coding genetic variation can have on the phenotypes that distinguish humans from each other and from our close evolutionary relatives. The full implications of this new understanding are largely unexplored, however, as modern ethics restricts experimentation in humans and most primates, rendering data from dynamic processes almost non-existent. The study of regulatory molecular dynamics has been changed entirely by the availability of protocols to generate iPSCs and differentiate them into adult cell types. The molecular basis of disease mechanisms, drug response, and developmental processes can now be studied in the relevant tissue, presenting an overwhelming spectrum of possible applications. Of particular interest to comparative biologists, long-standing questions about the relative conservation of early developmental states can now, for the first time, be ethically explored in closely related primates. In this dissertation, we first discuss evidence that iPSCs can faithfully model genetic variation, even when sourced from highly dysregulated cells. We then use an iPSC-based model to study the temporal profile of conservation between humans and chimpanzees during early endoderm development and identify patterns of divergence over developmental stages.

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