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Congenic mice reveal effect of SNP, genomic rearrangements and expression variation on genome wide gene expression

Noyes, H.A.; Agaba, M.; Ogugo, M.; Brass, A.; Anderson, S.; Archibald, A.; Fisher, P.; Hulme, H.; Rennie, K. and Kemp, S.J. (2007) Congenic mice reveal effect of SNP, genomic rearrangements and expression variation on genome wide gene expression. In: Genomics of Common Diseases Conference, 7-10 July 2007, Wellcome Conference Centre, Hinxton, UK. (Unpublished)

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Abstract

There is still no well-defined strategy for discovering the Quantitive Trait Genes (QTG) amongst the hundreds of candidates underlying Quantitive Trait Loci (QTL). We have created three congenic mouse lines that have C57BL/6 regions covering QTL for response to infection with Trypanosoma congolense introgressed into an A/J background. Data is presented here from the two parental strains and one of the congenic lines that carries a 16Mb region of C57BL/6 DNA spanning the murine MHC on chromosme 17. We have undertaken a systematic analysis of the effect of SNP, gene expression and genomic rearrangements within the congenic regions on genome wide gene expression. Gene expression data was collected using Affymetrix 430_2 mouse expression arrays and SNP data was from the Perlegen 8m SNP set http://mouse.perlegen.com/mouse/download.htm. This data has been used to identify the genes and pathways regulated by the congenic region and at the same time to identify genetic polymorphisms within the region that could plausibly regulate the differences in genome wide gene expression that we have observed. All classes of polymorphism within the QTL had detectable effects on both cis and trans gene expression. A genomic duplication within the QTL was associated with altered expression of Glo1 within the duplicated region. A Taverna workflow was used to identify pathways that had altered gene expression and that also contained genes within the QTL, the workflow identified Daxx as a candidate for regulating apoptosis pathways and resequencing identified an amino acid indel in the p53 interacting domain of Daxx. A GeneGo network analysis showed that the p53 pathway was the one that differed most between congenic mice and controls in the spleen and is regulated by Daxx.

Item Type:Conference or Workshop Item (Other)
Uncontrolled Keywords:Polymorphism; Congolense; Trypanosoma
Subjects:Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Faculty of Science > Department of Biological Sciences
Refereed:Yes
Status:Unpublished
ID Code:249
Deposited On:20 Apr 2010 14:25
Last Modified:05 Mar 2012 11:26

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