| Complex quantitative traits are measurable characteristics of living organisms resulting from the interaction between multiple genes and environmental factors. Genetic loci associated with complex trait are called "quantitative trait loci" (QTL). Recently, considering the expression levels of thousands of genes as quantitative traits, it has become possible to detect "expression QTLs" (eQTL). These eQTL are considered intermediate phenotypes and are used to better understand the biological architecture of complex traits. However the majority of studies still try to identify a causal mutation in a single gene. This approach can only meet success in situations where the gene incriminate as a major effect on the complex trait, and therefore can not elucidate the situations where complex traits result from interactions between various genes.;This thesis proposes a more comprehensive approach to: 1) take into account the possible interactions between multiple genes for the detection of eQTLs and 2) consider how polymorphisms affecting the expression of several genes in a module of co-expression may contribute to quantitative complex traits. Our contributions are as follows:;* We have developed a tool using multivariate analysis techniques to detect eQTLs, and have shown that this tool increases the sensitivity of detection of a particular class of eQTLs.;* Based on the data analysis of gene expression in recombinant inbred strains mice tissues, we have shown that some polymorphisms may affect the expression of several genes in domain of co-expression.;* Combining eQTLs detection studies with network of co-expression genes analysis in recombinant inbred strains mice, we showed that a genetic locus could be linked to both the expression of multiple genes at a domain of gene co-expression and a specific complex trait (i.e. left ventricular mass).;Our studies have detected several mechanisms by which genetic polymorphisms may be associated with the expression of several genes, and may themselves be linked to quantitative complex traits. |
