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Genomics approaches to trypanosomiasis resistance - some surprises

Kemp, Stephen Genomics approaches to trypanosomiasis resistance - some surprises. In: International Symposium on Animal Genomics for Animal Health., 23-25 October 2007, OIE HQ, World Organisation for Animal Health, Paris France. (Unpublished)

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Abstract

An international multidisciplinary consortium is conducting a programme of research into the host response to trypanosome infection. This builds upon QTL mapping which identified genome regions influencing susceptibility to pathology following T. congolense infection in both cattle and mouse. The approach uses expression analysis to examine the response of both susceptible and resistant strains and a series of novel informatics tools to identify pathways which are activated as a result of challenge, and those which are differentially used by resistant and susceptible strains. Of particular interest is those pathways which are significantly differentially activated and which contains genes within QTL regions. However, it is important to stress that we do require those genes to be differentially expressed themselves. Comparison of murine and bovine systems has proved highly informative. In particular, the use of congenic mouse lines in which fragments of resistant genome surrounding the QTL have been placed on a susceptible background has proved to be a powerful means of studying the action of QTL – and several trypanotolerance QTL co-localise to QTL involved in a range of other traits. We see a number of cases in which genes of susceptible origin show an altered pattern of expression as a result of a the presence of a distant gene of resistant origin. For example, a structural polymorphism within Notch4 within the QTL was correlated with altered expression of Dll4 a ligand of Notch4 on a different chromosome. In all cases, we find a gene network rather than a gene-by-gene approach to be highly informative and we see strong indications that survival or death is a result of differential use of number of very generic pathways. This is perhaps surprising and is turning out to have implications beyond trypanosomiasis into areas such as human survival following sepsis and under many other stresses.

Item Type:Conference or Workshop Item (Other)
Uncontrolled Keywords:Animal; Resistance; Trypanosomiasis; Response; Trypanosome; trypanosome infection; Infection; Pathology; Congolense; Congolense infection; Cattle; Mouse; analysis; Strains; Strain; Pathways; Pathway; GENE; Murine; bovine; trypanotolerance; TRAITS; Number; polymorphism; Survival; Human.
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:No
Status:Unpublished
ID Code:318
Deposited On:20 Apr 2010 15:00
Last Modified:20 May 2011 17:19

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