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DNA METHYLATION AS A BIOMARKER IN HUMAN REPRODUCTIVE HEALTH
AND DISEASE
by
Sahar Houshdaran
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(BIOCHEMISTRY & MOLECULAR BIOLOGY)
August 2009
Copyright 2009 Sahar Houshdaran
Object Description
| Title | DNA methylation as a biomarker in human reproductive health and disease |
| Author | Houshdaran, Sahar |
| Author email | houshdar@usc.edu; sahar.hooshdaran@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2009-03-25 |
| Date submitted | 2009 |
| Restricted until | Restricted until 10 Aug. 2011. |
| Date published | 2011-08-10 |
| Advisor (committee chair) | Laird, Peter W. |
| Advisor (committee member) |
Laird-Offringa, Ite A. Shibata, Darryl K. |
| Abstract | Epigenetics refers to the changes in gene expression that are not accounted for by the changes in DNA sequence. DNA methylation is one of the main epigenetic mechanisms in mammals. It contributes to various biological processes such as cellular differentiation, gametogenesis, and cancer. We investigated DNA methylation abnormalities in the male and female reproductive tract. During gametogenesis germ cells undergo epigenetic reprogramming, defects of which may lead to compromised spermatogenesis. Using MethyLight and Illumina GoldenGate assays we found a broad abnormal epigenetic defect associated with abnormal semen parameters. We propose that the underlying mechanism may be improper erasure of DNA methylation during germline reprogramming.; Ovarian cancer has the highest mortality rate of all gynecologic malignancies. Survival is strongly stage-dependent but there are no effective screening methods available. Ovarian cancer is also very heterogeneous. While each subtype presents with different clinical, pathological, and therapeutic characteristics, all ovarian cancer patients are treated uniformly. We used DNA methylation assays to investigate epigenetic differences between the subtypes and to find potential blood-based early detection biomarkers. We observed subtype-specific DNA methylation profiles suggesting that each subtype might be a distinct disease. Stepwise marker screening resulted in a panel of four markers that could distinguish pooled sera of patients from controls, but should be further investigated on multiple independent serum samples. |
| Keyword | DNA methylation; epigenetics; ovarian cancer; ovarian carcinoma; male infertility; sperm epigenetics |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m2560 |
| Contributing entity | University of Southern California |
| Rights | Houshdaran, Sahar |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-Houshdaran-2835 |
| Archival file | uscthesesreloadpub_Volume48/etd-Houshdaran-2835.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | DNA METHYLATION AS A BIOMARKER IN HUMAN REPRODUCTIVE HEALTH AND DISEASE by Sahar Houshdaran A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (BIOCHEMISTRY & MOLECULAR BIOLOGY) August 2009 Copyright 2009 Sahar Houshdaran |
