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.
|Commitee:||Clark, Marcus, Dolan, Eileen, Perera, Minoli, Stephens, Matthew|
|School:||The University of Chicago|
|Department:||Interdisciplinary Scientist Training Program: Human Genetics|
|School Location:||United States -- Illinois|
|Source:||DAI-B 78/05(E), Dissertation Abstracts International|
|Keywords:||Chimpanzee, Induced pluripotent stem cells|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be