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FUNCTIONAL CHARACTERIZATION OF COLORECTAL CANCER GWAS
LOCI
by
Gustavo Alfonso Mendoza-Fandiño
_____________________________________________________________
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
May 2013
Copyright 2013 Gustavo Alfonso Mendoza-Fandiño
Object Description
| Title | Functional characterization of colorectal cancer GWAS loci |
| Author | Mendoza-Fandiño, Gustavo Alfonso |
| Author email | gustavom@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biochemistry and Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2013-01-11 |
| Date submitted | 2013-02-18 |
| Date approved | 2013-02-19 |
| Restricted until | 2013-02-19 |
| Date published | 2013-02-19 |
| Advisor (committee chair) |
Stallcup, Michael Casey, Graham Tokes, Zoltan |
| Advisor (committee member) |
Coetzee, Gerhard Allayee, Hooman |
| Abstract | Genome-wide association studies (GWAS) have provided a powerful approach to identify CRC common disease variants. As of June 2012, 18 CRC loci have been identified in European populations. The predicted CRC risk associated with each variant is modest, opening the question how the remaining heritability could be explained. Identification of the true causal variant(s) within each locus is expected to explain part of the missing heritability of this disease and will help in the understanding of CRC genetic etiology. Their identification should also lead to an improvement in surveillance for this disease. Important regulatory elements are located in non-coding parts of the genome. We tested the hypothesis that functional enhancer elements within CRC associated loci contain gene regulatory activity and that a common variant within such regions could lead to the modulation of gene expression of a relevant gene(s). I characterized the enhancer regulatory landscape within the 19q13.1, 15q13.3, and 20q13.33 CRC risk loci using ChIP-seq of H3K4me1 and DNase1 HS data, and identified within chromosome 19q13.1 an enhancer regulatory element where the common variant rs7246814 was implicated as a functional variant. Furthermore, I showed a borderline correlation between rs7246814 and GPATCH1 gene expression level in normal colon epithelial tissues. In this study we provided suggestive evidence for the GPATCH1 gene as a candidate for CRC risk. |
| Keyword | GWAS; common variant; functional variant; enhancer elements |
| 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-m |
| Contributing entity | University of Southern California |
| Rights | Mendoza-Fandiño, Gustavo Alfonso |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume7/etd-MendozaFan-1441.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Full text | FUNCTIONAL CHARACTERIZATION OF COLORECTAL CANCER GWAS LOCI by Gustavo Alfonso Mendoza-Fandiño _____________________________________________________________ A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (BIOCHEMISTRY AND MOLECULAR BIOLOGY) May 2013 Copyright 2013 Gustavo Alfonso Mendoza-Fandiño |
