Date of Defense


Date of Graduation




First Advisor

John Spitsbergen

Second Advisor

Erik Larson

Third Advisor

Agata Parsons-Aubone


Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by a decrease or loss of the PKD1 gene product, polycystin 1. The regulators of PKD1 expression and genetic stability are undefined. We have discovered that the human, but not mouse, PKD1 gene encodes widespread G-quadruplex (G4) DNA structures: four-stranded conformations that are known to influence gene expression and mutagenesis in the genome. G4 DNA formation was investigated to determine its impact on the expression of PKD1 using a G4-stabilizing ligand in human (HEK293T) and mouse (IMCD3) cells. High resolution melt curves were generated for treated HEK cells and compared with standards to determine the degree of methylation. Between treatment (Phen-DC3, a G4-stabilizing ligand) and control (DMSO) groups, no noticeable difference in methylation status was observed. Real-time quantitative PCR was used to quantify mRNA for PKD1 for both treatment and control groups in HEK and IMDC3 cells. Beta-actin was used as a housekeeping gene to normalize the expression. Incubation of HEK and IMCD3 cells with Phen-DC3 resulted in a decrease in human PKD1 mRNA compared to loci that do not form G4 structures. PKD1 in IMCD3 did not show a significant decrease when treated with the same ligand, consistent with a lack of G4 structures in the mouse ortholog. As a result, the apparent formation of G4 DNA structures in human PKD1 has a direct impact on expression, resulting in decreased mRNA over time. Consequently, these structures may bring about a decrease in the PKD1 gene product and thus contribute to the onset of ADPKD.

Access Setting

Honors Thesis-Restricted

Restricted to Campus until


Available for download on Wednesday, December 18, 2024