Congenic mice infected with Trypanosoma congolense

1. Congenic mice infected with Trypanosoma congolense Harry Noyes University of Liverpool

2. 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 Participants • Roslin Institute • Alan Archibald • Susan Anderson • Laurence Hall

3. Mouse models of trypanotolerance . Survival of F6 and parental populations

4. Trypanosoma infection response (Tir) loci C57/BL6 x AJ and C57/BL6 x BALB/C Iraqi et al Mammalian Genome 2000 11:645-648 Kemp et al. Nature Genetics 1997 16:194-196

5. Microarray design for each condition Susceptible AJ Resistant C57BL/6

6. High throughput tissue collection

8. Correlation of expression and SNP in parental inbred lines Number of differentially expressed probes per 50 probe bin r2 = 0.1 Number of SNP in 1kb upstream of genes in each bin

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

10. Effect of copy number variation Poster 30

11. Effect of copy number variation on Glyoxalase1 expression

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

13. Survival of congenic mice

15. p53 Networks in Congenic Spleen

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

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

19. Cholesterol metabolism

20. Total Cholesterol levels

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

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

23. Total cholesterol responses in Intensive care n = 607 33% dead within 28 days

24. Results Analysis of early non-HDL cholesterol responses

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

26. RXRb protein by Western Blot

27. 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