Defense Date


Document Type


Degree Name

Master of Science


Human Genetics

First Advisor

Rita Shiang


Treacher Collins Syndrome (TCS) is a rare autosomal dominant disorder characterized by severe craniofacial defects. The syndrome is associated with mutations in the TCOF1 gene, which encodes a nucleolar phosphoprotein called treacle. Model organisms have been generated to model the disease and have revealed knowledge about the etiology and pathogenesis of the disorder. The craniofacial abnormality observed in TCS patients is found to be caused by an increased level of apoptosis in the neuroepithelium and from this it has been suggested that treacle is important for proper formation and proliferation of neural crest cells that will ultimately contribute to the face. The best attempt to rescue the phenotype of TCS was made by inhibiting the expression of p53 in both zebrafish and mouse models. Although both rescues were successful, it resulted in tumor formation in mice which limits the potential of using this type of rescue in humans. Therefore, it is very important to identify p53-downstream genes that were not 5 related to cancer and use them to interrupt the apoptosis pathway and hence rescuing the phenotype.


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VCU Theses and Dissertations

Date of Submission

July 2009