Document Type

Thesis

Date of Degree

2012

Degree Name

MS (Master of Science)

Degree In

Chemical and Biochemical Engineering

First Advisor

Robert A. Philibert

Second Advisor

Mani Subramanian

Abstract

The serotonin transporter (SLC6A4) has been a prominent choice in studying multiple neuropsychiatric illnesses. However, underlying molecular mechanisms of the regulatory control of this gene leading to these illnesses remain incomplete. Since this locus is the target of virtually every antidepressant, understanding the molecular mechanisms would benefit the development of effective therapeutic agents.

In an attempt to better understand the regulatory control of the human serotonin transporter, a series of investigations were conducted on the 5HTTLPR genotype, DNA methylation and SLC6A4 mRNA expression with respect to childhood sexual abuse and depression. Moreover, since vast majority of studies have only concentrated on the Long (L) and Short (S) polymorphisms, the characteristics of the Extra-Long (XL) allele with respect to transcriptional efficiency was investigated. Finally, due to the increase in gene expression studies, the normalization of gene expression with respect to multiple housekeeping genes was explored.

Through this study, we demonstrate significant gene-environmental interaction effects at this locus. The extra-long variant was associated with increased gene transcriptional efficiency. Also, although the best gene expression normalization was achieved with one housekeeping gene, we present a strong explanation on the importance of utilizing more than one housekeeping gene. These results could certainly aid in understanding and treating disorders related to the human serotonin transporter.

Keywords

childhood sexual abuse, depression, epigenetics, gene expression, methylation, serotonin transporter

Pages

vii, 54 pages

Bibliography

Includes bibliographical references (pages 48-54).

Copyright

Copyright 2012 Meeshanthini Vijayendran

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