Honors Capstone Project
Date of Submission
Stephen Glatt, Ph.D Assistant Professor Upstate Medical University
John Belote, Ph.D Professor Syracuse University
Arts and Science
Capstone Prize Winner
Won Capstone Funding
Sciences and Engineering
Biological Psychology | Biology | Psychology
Schizophrenia is a disorder that affects 1% of the population and causes enormous deficits in functioning. The development of this disorder is through unclear mechanisms, yet studies suggest that genetics and dopamine processes play a major role in the manifestation of schizophrenia. This study considers the gene that encodes dopamine receptor D2 (DRD2) and how single nucleotide polymorphisms (SNPs) affect alternative splicing of the gene and the balance between the two different protein isoforms, Long (D2L) and Short (D2S). Four mutations (rs12363125 and rs2511521 from intron 5 and rs6275 and rs6277 from exon 7) were studied. Constructs were derived from extracted DNA from postmortem brain tissue of Brodmann’s Area 10 of deceased patients with schizophrenia and non-psychiatric comparison subjects. Enzyme digests and ligations of patient DNA were used to create constructs that have a spectrum of mutation combinations. Quantitative polymerase chain reaction (qPCR) analysis was used to measure the proportional expression of the different isoforms. A linear regression model with an r2of 0.255 showed that more than 25% of the variance in D2L to D2S expression ratios (L/S Ratios) were attributable to SNPs, and rs6275 and rs6277 were found to independently and significantly affect L/S Ratios expressed by cells, with p
Paish, Lauren, "DRD2 Polymorphisms Imparting Risk for Schizophrenia" (2012). Syracuse University Honors Program Capstone Projects. 148.
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