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Modelling genetic and genomic interactions underlying gene expression and complex traits

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Langley-SR-2013-PhD-Thesis.pdf7.4 MBAdobe PDFView/Open
Langley-SR-2013-PhD-Thesis-Appendix-A-FigureA1 Distribution of Phenotypes.pdf297.56 kBAdobe PDFView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-FigureB1 Genome wide QTL scans.pdf2.06 MBAdobe PDFView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-FigureB2 Convergence of eQTLs.pdf17.88 MBAdobe PDFView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB1 List of all eQTLs.xlsx2.12 MBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB2 List of trans clusters.xlsx5.91 MBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB3 Trans cluster master regulators.xlsx34.05 kBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB4 Functional enrichment for trans clusters.xlsx42.5 kBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB5 QTT by Tissue.xlsx42.88 kBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB6 QTT results for all tissues.xlsx21.43 MBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB7 KEGG enrichment of eQTLs.xlsx32.15 kBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB8 KEGG enrichment of NGC.xlsx31.36 kBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB9 3C Genes.xlsx54.85 kBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB10 Human GWAS genes.xlsx107.57 kBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB11 Human Rat Orthologs.xlsx361.85 kBMicrosoft ExcelView/Open
Langley-SR-2013-PhD-Thesis-Appendix-B-TableB12 Rat-Human Candidate Genes.xlsx328.61 kBMicrosoft ExcelView/Open
Title: Modelling genetic and genomic interactions underlying gene expression and complex traits
Authors: Langley, Sarah Raye
Item Type: Thesis or dissertation
Abstract: This study focuses on integrating and applying computational techniques for modelling quantitative traits and complex diseases, such as hypertension and diabetes, using the rat model system and translating the findings to humans. Complex disease traits are heritable, highly polygenic, and influenced by environmental factors. Human studies, like Genome Wide Association Studies (GWAS), have identified many genetic determinants underlying these traits but have provided little information about the functional effects of these variants and mechanisms regulating the disease. This study takes a systems-level approach for looking at the genetic regulation of complex traits in the rat by analysing multiple phenotypes, genomewide genetic variation and gene expression data in multiple tissues. I integrated these multi-modality datasets in the BXH/HXB rat Recombinant Inbred (RI) lines, an established model of the human metabolic syndrome, to identify candidate genes, pathways and networks associated with complex disease phenotypes. I evaluated methods for Expression Quantitative Trait Locus (eQTL) analysis and used sparse Bayesian regression approaches to map eQTLs in the RI lines, delineating a new, large eQTL data resource for the rat genetic community. I have also developed and applied signal processing and time series analysis methods to physiological traits to extract more detailed indices of blood pressure, and integrated these with genetic, expression and eQTL data to inform on the regulation of these traits. Then, using publicly available data, I used comparative genomics approaches to elucidate a set of genes and pathways that can play a role in human diseases. This study has provided a valuable resource for future work in the rat, by means of new eQTLs in multiple tissues, and physiological time series phenotypes and approaches. This has enabled an integrative analysis of these data to give new insights into the regulation of complex traits in rats and humans.
Issue Date: Dec-2012
Date Awarded: Jan-2013
URI: http://hdl.handle.net/10044/1/10925
DOI: https://doi.org/10.25560/10925
Supervisor: Aitman, Tim
Petretto, Enrico
Richardson, Sylvia
Sponsor/Funder: Wellcome Trust (London, England) ; Medical Research Council (Great Britain)
Department: Institute of Clinical Science
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Department of Clinical Sciences PhD Theses

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