Advisor Casey, Graham (committee chair), Stallcup, Michael R. (committee chair), Tokes, Zoltan A. (committee chair), Allayee, Hooman (committee member), Coetzee, Gerhard (Gerry) A. (committee member)

Creator Email gustavom@usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c3-220618

Unique identifier UC11293528

Identifier usctheses-c3-220618 (legacy record id)

Legacy Identifier etd-MendozaFan-1441.pdf

Dmrecord 220618

Document Type Dissertation

Rights Mendoza-Fandiño, Gustavo Alfonso

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

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 a...

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA

Abstract (if available)

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.