Defense Date

2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Bioinformatics

First Advisor

Vladimir Vladimirov

Abstract

The last decade has seen considerable research focusing on understanding the factors underlying schizophrenia and bipolar disorder. A major challenge encountered in studying these disorders, however, has been the contribution of genetic, or etiological, heterogeneity to the so-called “missing heritability” [1-6]. Further, recent successes of large-scale genome-wide association studies (GWAS) have nonetheless seen only limited advancements in the delineation of the specific roles of implicated genes in disease pathophysiology. The study of microRNAs (miRNAs), given their ability to alter the transcription of hundreds of targeted genes, has the potential to expand our understanding of how certain genes relate to schizophrenia and bipolar disorder. Indeed, the strongest finding of one recent mega-analysis by the Psychiatric GWAS consortium (PGC) was for a miRNA, though little can be said presently about its particular role in the etiologies of schizophrenia and bipolar disorder [52]. Next generation sequencing (NGS) is a versatile technology that can be used to directly sequence either DNA or RNA, thus providing valuable information on variation in the genome and in the transcriptome. A variation of NGS, MicroSeq, focuses on small RNAs and can be used to detect novel, as well as known, miRNAs [26,125, 126]. The following thesis describes the role of miRNAs in schizophrenia and bipolar disorder in various experimental settings. As an index of the interaction between multiple genes and between the genome and the environment, miRNAs are great potential biomarkers for complex disorders such as schizophrenia and bipolar disorder.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

October 2012

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