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Title page for ETD etd-06202005-085733


Type of Document Dissertation
Author Fentress, Hugh Montrell
Author's Email Address hugh.fentress@vanderbilt.edu
URN etd-06202005-085733
Title Human 5-HT2C receptor variants: functional properties and genetic associations in major depressive disorder
Degree PhD
Department Neuroscience
Advisory Committee
Advisor Name Title
Randy Blakely Committee Chair
Alfred George Committee Member
Elaine Sanders-Bush Committee Member
Rich Breyer Committee Member
Ronald Emeson Committee Member
Keywords
  • GPCR
  • RNA editing
  • 5-HT2C receptor
  • serotonin
  • depression
  • SNP
Date of Defense 2005-05-27
Availability unrestricted
Abstract
This dissertation describes pharmacological studies of the functional consequences of the Cys23Ser single nucleotide polymorphism (SNP) in two different edited versions of the human 5-HT2C receptor as well as evaluation of this SNP in a population of well characterized depressed patients. I discovered that the Cys23Ser SNP has no functional consequences when expressed in a variety of cells in culture, although there were positive associations with endophenotypes of major depressive disorder (MDD). Upon examining other SNPs that could be in linkage disequilibrium with the Cys23Ser SNP, I found that a functional SNP in the 5-HT2C promoter (-697G/C) is closely linked to the Cys23Ser SNP. Therefore, these results suggest the non-functional Cys23Ser SNP associates with disease states because it is closely linked to the functional -697G/C promoter polymorphism in the 5-HT2C receptor.
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