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ndltd-OhioLink-oai-etd.ohiolink.edu-case12948728712021-08-03T05:33:51Z Dissecting Genetic Basis of Complex Traits by Haplotype-based Association Studies and Integrated Information from Multiple Data Sources Chen, Yixuan <p>Characterization of genetic variation and dissection of genetic architectures of complex diseases is critical in understanding their intrinsic mechanisms. Haplotype methods have shown improved power and more consistent results comparing to single-locus based approaches. We propose a new haplotype-based association method for family data. Our approach (termed F_HapMiner) first infers diplotype pairs of each individual in each pedigree assuming no recombination within a family. A phenotype score is then defined for each founder haplotype. Finally, F_HapMiner applies a clustering algorithm on founder haplotypes based on their similarities and identifies haplotype clusters that show significant associations with diseases/traits. Comparisons with single-locus and haplotype-based Transmission Disequilibrium Test (TDT) methods demonstrate that our approach consistently outperforms the TDT-based approaches regardless of disease models, local Linkage Disequilibrium (LD) structures or allele/haplotype frequencies.</p><p>Traditional linkage analysis and association study may result in hundreds of candidate genes. We propose an expandable framework for gene prioritization that can integrate multiple heterogenous data sources by taking advantage of a unified graphic representation. Gene-gene relationships and gene-disease relationships are then defined based on the overall topology of each network using the diffusion kernel measure. These relationship measures are in turn normalized to derive an overall measure across all networks, which is utilized to rank all candidate genes. Based on the informativeness of available data sources with respect to each specific disease, we also propose an adaptive threshold score to select a small subset of candidate genes for further validation studies. We performed large scale cross-validation analysis using three data sources based on protein interactions, gene expressions and pathway information. Results have shown that our approach consistently outperforms other two state-of-the-art programs. A web tool has been implemented to assist scientists in their genetic studies.</p><p>Researchers commonly rely on simulated data to evaluate their approaches for detecting high-order interactions in disease gene mapping. A publicly available simulation program is of great interests. We have developed a computer program gs to quickly generate a large number of samples based on real data. Two approaches have been implemented to generate dense SNP haplotype/genotype data that share similar local LD patterns as those in human populations. The first approach takes haplotype pairs from samples as inputs, and the second approach takes patterns of haplotype block structures as inputs. The improved version of gs provides great functionalities and flexibilities to simulate various interaction models. Data generated can serve as a common ground to compare different approaches in detecting interactions.</p> 2010 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1294872871 http://rave.ohiolink.edu/etdc/view?acc_num=case1294872871 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
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NDLTD
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English
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NDLTD
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| author |
Chen, Yixuan
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Chen, Yixuan
Dissecting Genetic Basis of Complex Traits by Haplotype-based Association Studies and Integrated Information from Multiple Data Sources
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Chen, Yixuan
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Chen, Yixuan
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| title |
Dissecting Genetic Basis of Complex Traits by Haplotype-based Association Studies and Integrated Information from Multiple Data Sources
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| title_short |
Dissecting Genetic Basis of Complex Traits by Haplotype-based Association Studies and Integrated Information from Multiple Data Sources
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| title_full |
Dissecting Genetic Basis of Complex Traits by Haplotype-based Association Studies and Integrated Information from Multiple Data Sources
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| title_fullStr |
Dissecting Genetic Basis of Complex Traits by Haplotype-based Association Studies and Integrated Information from Multiple Data Sources
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| title_full_unstemmed |
Dissecting Genetic Basis of Complex Traits by Haplotype-based Association Studies and Integrated Information from Multiple Data Sources
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| title_sort |
dissecting genetic basis of complex traits by haplotype-based association studies and integrated information from multiple data sources
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| publisher |
Case Western Reserve University School of Graduate Studies / OhioLINK
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| publishDate |
2010
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| url |
http://rave.ohiolink.edu/etdc/view?acc_num=case1294872871
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| work_keys_str_mv |
AT chenyixuan dissectinggeneticbasisofcomplextraitsbyhaplotypebasedassociationstudiesandintegratedinformationfrommultipledatasources
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1719421805341442048
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