Uniform TitleCandidate gene and microRNA expression studies of schizophrenia
NameBruse, Shannon E. (author), Rongo, Christopher (chair), Brzustowicz, Linda (internal member), Firestein, Bonnie (internal member), Buyske, Steve (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectMicrobiology and Molecular Genetics,
DescriptionSchizophrenia is a debilitating psychiatric disorder affecting 0.5-1% of the world's population. Schizophrenia has a significant genetic component, but the early search for specific genes has been slowed by a number of factors, including a lack of inexpensive genotyping methods suitable for targeted genetic studies. This work describes the development of an inexpensive multiplexed genotyping assay ideal for candidate gene studies. Furthermore, we describe application of this technology to the study of three schizophrenia candidate genes - SNAP-25, ZDHHC8, and DGCR8. Both SNAP-25 and ZDHHC8 are involved in glutamate signaling at the NMDA receptor, and dysfunction in glutamate signaling at the NMDA receptor is one of the leading theories of the etiology of schizophrenia. DGCR8 is an RNA-binding protein necessary for the processing of microRNAs, a class of small RNAs important in the development and maintenance of the mammalian central nervous system. Though we failed to find evidence of genetic association with ZDHHC8, we did identify a genetic association between schizophrenia and variants within both the SNAP-25 and DGCR8 genes. Our results with DGCR8 provide the first genetic link between the microRNA biogenesis pathway and a major neuropsychiatric disorder. Additionally, we performed quantitative microRNA expression profiling in post-mortem brain samples from patients with schizophrenia, bipolar disorder, and psychiatrically normal controls. We began with a pilot study comparing the expression of 158 microRNAs in the dorsolateral prefrontal cortex (BA9) of post-mortem brain tissue. Based on initial results, we assessed the expression of a number of specific microRNAs in a large, well characterized sample set from patients with schizophrenia (n=35), bipolar disorder (n=35), and psychiatrically normal controls (n=35). In the larger sample set, we observed overexpression of one microRNA, hsa-mir-372. This overexpression was observed in two separate brain regions from patients with both schizophrenia and bipolar disorder, though no differential expression of any microRNA tested was deemed statistically significant.
NoteIncludes bibliographical references (p. 102-110).
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.