1. Genome responses of trypanosome infected cattle The encounter between cattle and trypanosomes elicits changes in the activities of both genomes - that of the host and that of the parasite. These changes determine the fate of the host and parasite and the outcome of the encounter. Although the outcome in most cattle is a slow death following progressive anaemia and loss of body condition, in other cattle the outcome is more favourable; these cattle regain the initiative, suppress parasite growth, recover from the initial clinical signs, gain weight, and reproduce normally. Cattle exhibiting this latter outcome are said to be trypanotolerant. Below is a synopsis of the genome responses that set apart the trypanotolerant cattle from the susceptible cattle during experimental trypanosome infection MetaCore GeneGo was used to identify networks amongst the genes that were differentially expressed. The figure (right) shows the largest network of connected genes that were differently expressed by trypanosome infected resistant (N’Dama) and susceptible (Boran) cattle. STAT3 and c-Fos have the most connectivity. STAT3 is a transcription factor which is activated in response to the IL-6 family of cytokines and is involved in the acute phase response in the liver Interestingly, STAT3 is modulated by RAC1 which is in turn controlled by VAV1 and ARHGAP15 which are both located in the QTLs controlling trypanotolerance.  Trypanosome infection induces profound changes in the genome function manifested by changes in the steady state level of many genes.  The differences in the genome responses of resistant and susceptible cattle correspond to some of the phenotypic attributes that correlate with susceptibility. In this study, twenty N’Dama (tolerant) cattle and 20 Boran (susceptible) cattle were experimentally infected with a lethal dose of T. congolense IL1180. Liver biopsy samples were taken from each individual in specified days prior to and post infection such that at each time point there were samples from at least 5 Boran and 5 N’Dama (A). The mRNA profiles in the biopsy material were assayed using the Affymetrix system (B). The gene data were fed into an analysis workflow (C) that integrates the expression measures, gene ontology, QTL information, and gene pathways data. BC A The Affy chips contained 24K probe sets. Of these between 600 and 750 probes were differently expressed between infected and uninfected cattle. Principle component analysis of the expression data clearly shows genome-wide differences between the transcriptomes of tolerant (  ) and susceptible ( ) cattle (Top Right, PCA component 3) and some of these differences are associated with the presence and progression of trypanosome infection (Top left, PCA component 1). Agaba M 1 Hulme H 2 Rennie C 3 Mwakaya J 1 Ogugo M 1 Brass A 2 Kemp SJ 1,3 Addresses 1 International Livestock Research Institute, Box 30709 - 00100, Nairobi Kenya 2 The University of Manchester LF8 Kilburn Bldg, Oxford Rd Manchester M13 9PL UK 3 School of Biological Sciences, University of Liverpool, Liverpool, L69 7ZB, UK Acknowledgements: We thank all the staff at the ILRI large animal facility and all colleagues in the Welcome Trust Consortium This work was supported by the Wellcome Trust. Data from an experiment showing the expression of thousands of genes on a single GeneChip® probe array. Image courtesy of Affymetrix.