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High resolution mapping of genetic loci underlying variation in gene expression using a heterogeneous stock of mice (HS GENOMICS)
Start date: 01 Aug 2007, End date: 31 Jul 2009 PROJECT  FINISHED 

Many traits of biomedical interest can be modelled in the mouse and are known to arise from a complex interaction of quantitative trait loci (QTL) and environment. Yet, despite intense efforts, in the majority of cases the identity of the relevant genes remains obscure. Genetical genomics, the mapping of genetic factors contributing to variation in mRNA transcript abundance, is emerging as a powerful new tool for the molecular dissection of complex traits. Here I propose a project using the outbred, genetically heterogeneous stock (HS) of mice together with Prof. Flint in Oxford. By analyzing expression levels in 500 liver samples I will be able to map loci to intervals of approximately 250 kilobases, sufficient to identify the responsible genes. Importantly, by combining the information from gene expression, genetics and phenotypes it will be possible to determine the likely pathway from gene to phenotype. This work will give new insights into gene regulation and provide important implications for our understanding of the genetic basis of complex traits. I have an excellent training in molecular biology, genetics and immunology and need to improve my skills in statistical and bioinformatical analysis and to broaden my understanding of other complex traits. For this purpose the group of Prof. Flint would provide an excellent opportunity for me to achieve my goals. The proposed project combines my experience in microarray with the expertice of Prof. Flint on genetic analysis in outbred mice. The training will complement my skills in mouse genetics and I will be able to control the whole process, from breeding set-up to statistical analysis in both inbred and outbred mice. Altogether, this will promote my independence and reinforce my professional maturity, and the fellowship would help me reach my goal to become an independent researcher with a long lasting scientific career.
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