Date of Award
Master of Science (MS)
Physics and Astronomy
Dr. Emil Alexov
Dr. Hugo Sanabria
Dr. Feng Ding
As genetic technology and information become continuously more sophisticated and applied to the prevention and treatment of diseases, the need to understand the effects of genetic variants becomes an important task with regards to assessing disease risk. In the specific case of intellectual disabilities, prenatal screenings is an important diagnostic tool that prepares families and health professionals for the arrival of a child who may need immediate, specialized care. Cell Free DNA screenings are routine for determining sex and provide the opportunity to discover genetic anomalies. However, this has little value unless mutations can be recognized as pathogenic and are correlated to the appropriate condition. In an attempt to provide such information and develop an appropriate protocol for predicting the pathogenicity of missense mutations, we present research conducted on mutations occurring within the Spermine Synthase (SpmSyn) and Spermidine Synthase (SpdSyn) proteins.
Mutations located in these proteins have been linked to severe intellectual disabilities such as Smith-Magenis Syndrome and Snyder-Robinson Syndrome as well as conditions of macrocephaly. While the pathogenicity of mutations located close to the active site of the proteins are easily predicted, those located elsewhere have pathogenicity determined mostly through association studies. By taking a physics based approach, we expect to overcome such a deficiency and to predict pathogenicity of mutations far away from the active site. This is done by modeling the effects of mutations on the homo-dimerization of the above proteins, since it is known that they function as homodimers.
Bonomi, Shannon, "Prediction of Pathogenic Mutations in Spermine/Spermidine Synthases" (2022). All Theses. 3747.