Congenic mice infected with Trypanosoma congolense Harry Noyes University of Liverpool

Participants ILRI, Nairobi Morris Agaba John Gibson Olivier Hanotte Steve Kemp Hassan Musa Joel Mwakya Daniel Mwanga Jan Naessens Joseph Nganga Moises Ogugu John Wambugu University of Manchester Andy Brass Helen Hulme Leo Zeef Leanne Wardlesworth University of Liverpool Anthea Broadhead Derek Daly Harry Noyes Katie Rennie Luke Thomas Roslin Institute Alan Archibald Susan Anderson Laurence Hall

Mouse models of trypanotolerance. Survival of F6 and parental populations

Trypanosoma infection response (Tir) loci C57/BL6 x AJ and C57/BL6 x BALB/C Iraqi et al Mammalian Genome : Kemp et al. Nature Genetics :

Microarray design for each condition Resistant C57BL/6Susceptible AJ

High throughput tissue collection

Correlation of expression and SNP in parental inbred lines Number of differentially expressed probes per 50 probe bin Number of SNP in 1kb upstream of genes in each bin r 2 = 0.1

Relative Risk of Differential Expression Only genes with tightly regulated expression (p<0.005) were associated with SNP

Effect of copy number variation Poster 30

Effect of copy number variation on Glyoxalase1 expression

C57BL/6 regions carried by congenics C57BL/6 regions in Tir 1 congenics Tir 2 congenics Tir 3 congenics

Survival of congenic mice

p53 Networks in Congenic Spleen

QTL workflow Given a species, chromosome, Affymetrix Array Name, Start and Stop position, Get back the EnsEMBL Gene ids Get EnsEMBL Gene ids Retrieve a list of Information about each EnsEMBL Gene id Extract the SwissProt ids from this Gene information list Send gene ids and uniprot accesion numbers off to KEGG and retrieve a KEGG id Remove any null values Send swissprot ids to NCBI and get gene ids Send kegg gene ids off to KEGG and retrieve a pathways Merge pathways into a single text file Merge pathways ids with gene ids Fisher et al. NAR 2007

Polymorphism in Daxx in hyperacidic region C57BL/6ETDDDDDDDDDDDDEDNEESEEEEEEEEEE 129/J D BALB/c A/J

Cholesterol metabolism

Total Cholesterol levels

Survival of C57BL/6ByJ C57BL/6ByJ spontaneous mutant with low cholesterol and low risk of atherosclerosis

Paul Dark Infection, Injury and Inflammation Research Group Hope Hospital Intensive Care Unit The University of Manchester, UK

Total cholesterol responses in Intensive care n = % dead within 28 days

Results Analysis of early non-HDL cholesterol responses

NATURE MEDICINE VOLUME 9 NUMBER 2 FEBRUARY 2003 LXR agonists lower cholesterol and inhibit NFkB mediated inflammatory signals

RXRb protein by Western Blot

Conclusions Glo1 gene duplication may be associated with differences in oxidative stress Daxx aspartate polymorphism may regulate apoptosis RXRb expression differences may be associated with regulation of cholesterol and inflammation