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Title: Genetic mapping and microarray analyses to identify factors associated with a mouse obesity QTL region
Author: Stylianou, Ioannis Mastroufis
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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Previously, the discovery of four body fat quantitative trait loci (QTL) had been reported in an F2 cross between the long-term divergently selected fat (F) and lean (L) – lines of mice, differing five-fold in total body fat. A congenic line for the Fob3 QTL region on mouse chromosome 15 (mChr15) was generated by backcrossing the L-line QTL region to the F-line using marker assisted selection. This thesis reports the use of this line in a more detailed QTL mapping analysis revealing that the Fob3 QTL is a constituent of at least two smaller QTL (Fob3a and Fob3b) with effects at different developmental stages. The analysis demonstrates the genetic complexity involved in polygenic traits such as obesity where even small effects on a trait can be affected by multiple loci. Additionally, a microarray approach has been used to compare gene expression differences in liver and brown adipose tissue between the F-line and a Fob3b-containing congenic line. Using 15,000 cDNAs, this microarray analysis identified several unknown and known mChr15 differentially expressed transcripts. Differential expression of genes on non-mChr15 chromosomes highlights the Fob3b has an effect on the cholesterol biosynthesis pathway, and possibly also the glycolysis pathway. Northern analysis was used to confirm the microarray results for the most promising candidates and to perform a detailed developmental and tissue distribution analysis on the unknown mChr15 differentially expressed transcripts, whilst q-PCR has been used to confirm the candidates involved in the cholesterol biosynthesis pathway. The analysis demonstrates the use of microarrays as a powerful tool to identify perturbed metabolic pathways that could help in future functional characterisation of causal genes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available