Quantitative trait loci (QTL) mapping in outbred populations faces some challenges unique to the divergent genetic background and complex pedigree relationships. Motivated by a dairy cattle half-sib data set from a grand daughter design, we present in this dissertation a series of endeavors to address various challenges along the analysis flow of QTL mapping. A first step is to infer the haplotypes in sires based on the observed genotypes in sires and his offspring. Our method was shown to outperform peer methods with greater robustness and accuracy yet with fast speed performance. Then in light of adapting the multiple interval mapping method to within-family QTL analysis, we extended the modeling framework by allowing for heteroscedastic residual variances and upgraded the Windows QTL Cartographer accordingly. The advantageous post-analysis result parsing from Windows QTL Cartographer and more importantly, the improved analysis outputs due to more powerful maximum likelihood-based mixture modeling than the least squares regression manifest our efforts in delivering better methodology via practically user friendly software. We further developed a mixed model approach for the purpose of QTL mapping across multiple families that was aimed at modeling QTL effects as both the fixed effect across families and the random effect within families. Our mixed model was shown to encompass similar or higher statistical testing performance on QTL variation than the widely used variance component modeling approach, yet still allowing permutations for obtaining chromosome-wide or genome-wide significance threshold. What's more, the flexibility of our mixed model in constructing alternative hypotheses testing on either fixed or random QTL effects or both was shown to offer interesting insight into the varying sources of signal that would not be unveiled by least squares regression or variance component methods. In concluding our comprehensive approach to QTL linkage mapping in dairy cattle populations, we continue to explore methods of fine mapping by combining both the linkage disequilibrium and linkage information and prospective method improvements are being sought.
| Identifer | oai:union.ndltd.org:NCSU/oai:NCSU:etd-05042009-160015 |
| Date | 20 May 2009 |
| Creators | Gong, Xiaohua |
| Contributors | Zhao-Bang Zeng, Melissa Ashwell, Wenbin Lu, Steffen Heber |
| Publisher | NCSU |
| Source Sets | North Carolina State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://www.lib.ncsu.edu/theses/available/etd-05042009-160015/ |
| 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, dis sertation, 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 NC State 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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