Page 1 |
Save page Remove page | Previous | 1 of 188 | Next |
|
small (250x250 max)
medium (500x500 max)
large ( > 500x500)
Full Resolution
All (PDF)
|
This page
All
Subset |
AN INTEGRATIVE APPROACH FOR DETERMINING AGE RELATED
MACULAR DEGENERATION RISK FACORS IN LATINOS
by
Corina Julia Shtir
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
(BIOSTATISTICS)
May 2009
Copyright 2009 Corina Julia Shtir
Object Description
| Title | An integrative approach for determining age related macular degeneration risk facors in Latinos |
| Author | Shtir, Corina Julia |
| Author email | stir@usc.edu; corina@shtir.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biostatistics |
| School | Keck School of Medicine |
| Date defended/completed | 2008-12-17 |
| Date submitted | 2009 |
| Restricted until | Unrestricted |
| Date published | 2009-04-07 |
| Advisor (committee chair) | Azen, Stanley |
| Advisor (committee member) |
Marjoram, Paul Gauderman, Jim Varma, Rohit Humayun, Mark |
| Abstract | Age-related macular degeneration (AMD) is the leading cause of blindness among elderly individuals worldwide. Previous studies confirmed different frequencies between ethnic groups for a series of risk alleles and a pressing need to determine unidentified genetic factors characterizing the pathogenesis of AMD. This study seeks to identify new genes associated with risk for developing early AMD among Latinos, through the use of a genome wide association study (GWAS) and through a copy number variation (CNV) analysis that is based on a series of proposed CNV association tests. In addition, we performed a population admixture study based on 233 ancestry informative markers.; GWAS was conducted using single allele and haplotype trend regression tests. Our overall results include a series of variants involved in oxidative stress and inflammatory mechanisms that interact with the complement system. In contrast to Caucasian based AMD pathways we identified a neurodevelopment and brain injury repair mechanism that may constitute an essential and novel role in the biogenesis of AMD among Latinos. Also, we proposed a series of segment- and gene-based CNV association tests. In order to compare CNV estimates of different algorithms we apply the GADA and CNAM programs, and further report how the normalizing techniques, mean segment estimates, and copy number association tests differ. We found wide discrepancies between SNP hybridization normalization techniques, which in turn affect all downstream CNV analyses.; Given the strong effect of population admixture on genetic association studies, we estimated the ancestral load of LALES Latinos by comparing it to its founder populations. We detected strong evidence for recent population admixture in LALES Latinos, with overall estimates of 45.5% Native American, 40.1% European, 9.8% Asian, and 4.5% African-American ancestry. Gradients of increasing Native American background (37.3% to 51.7%) and of correspondingly decreasing European ancestry (45.3% to 29.6%) were observed as a function of birth origin from North to South. The strongest excess of homozygosity, a reflection of recent population admixture, was observed in non-US born Latinos that recently populated the US. In conclusion we summarize the lessons we have learned from integrating GWAS, CNV, and Population Admixture studies. |
| Keyword | population admixture; age related macular degeneration; Latinos; GRAS; CNV |
| 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-m2057 |
| Rights | Shtir, Corina Julia |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Shtir-2764 |
| Archival file | uscthesesreloadpub_Volume40/etd-Shtir-2764.pdf |
Description
| Title | Page 1 |
| Full text | AN INTEGRATIVE APPROACH FOR DETERMINING AGE RELATED MACULAR DEGENERATION RISK FACORS IN LATINOS by Corina Julia Shtir 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 (BIOSTATISTICS) May 2009 Copyright 2009 Corina Julia Shtir |
Comments
Post a Comment for Page 1
