Recent advances in single nucleotide polymorphism (SNP) genotyping techniques, public databases, and genomic knowledge via the Human Genome Project and the Haplotype Mapping project (HapMap) allow for true genome-wide association (GWA) analysis for common complex diseases such as heart disease, diabetes, and Alzheimers. A major obstacle in genome-wide association analysis is the prohibitively high cost of projects that require genotyping hundreds, even thousands, of individuals in order to achieve appropriate statistical significance. One potential solution to the prohibitive cost is to combine or pool the DNA of case and control individuals and to use pooled genotyping or allelotyping for association analysis by determining the genotype allele frequency differences between case and control populations. While pooling can dramatically increase efficiencies by lowering cost and time, it also introduces additional sources of error and noise.
In this study, we comparatively examine DNA pooled genotyping versus individual genotyping for genome-wide association analysis of complex disease. Our work has created a system and process that allows for the direct evaluation and comparison of pooled genotyping versus individual genotyping by using and modifying existing bioinformatics tools. Our results show that pooled GWA studies are limited to resolving complex disease with medium to high relative risks ratios. Pooling errors have a very large effect on the overall statistical significance of a pooled GWA. Genotyping errors have a modest effect on pooled and individual GWA which is much less in magnitude to pooling errors.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07202007-124602 |
| Date | 24 July 2007 |
| Creators | Pratap, Siddharth |
| Contributors | Shawn Levy, Daniel Masys, Jay Snoddy, Scott M. Williams |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07202007-124602/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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