Valid XHTML 1.0 Strict

Functional Genomics of Trypanosomiasis

Most recent publications

2013

PDF OF PAPER

Whole-Genome Sequencing of Trypanosoma brucei Reveals Introgression between Subspecies That Is Associated with Virulence Ian Goodhead, Paul Capewell, J. Wendi Bailey, Tanja Beament, Michael Chance, Suzanne Kay, Sarah Forrester, Annette MacLeod, Mark Taylor, Harry Noyes, Neil Hall. mBio (2013) 4(4)e00197-13. doi:10.1128/mBio.00197-13

2012

PDF OF PAPER

Novel SNP Discovery in African Buffalo, Syncerus caffer, Using High-Throughput Sequencing le Roex N, Noyes H, Brass A, Bradley DG, Kemp SJ, et al. (2012) PLoS ONE 7(11): e48792. doi:10.1371/journal.pone.0048792

A complete list of Publications

Objectives of the project

This Wellcome Trust funded project is being undertaken by a consortium of five centres, the Universities of Liverpool, Manchester and Edinburgh, the Roslin Institute in Midlothian and the International Livestock Research Institute (ILRI) in Nairobi.

This multi-disciplinary, multi-centre project is a collaboration between molecular biologists, genetic scientists, bioinformaticians and parasitologistsis to identify the genes which control resistance to Trypanosoma congolense in both mice and cattle. Five regions of the mouse genome and ten regions of the cattle genome known as Quantative Trait Loci (QTL) have been found to be associated with resistance.

There are thousands of genes in these QTL regions and identifying the ones that cause the difference in response to infection is a major challenge. We are using microarrays that measure how much of each gene in a sample is being used to discover the gene networks that respond to infection and especially those that respond differently. We are developing new methods to analyse these data so that we can identify genes in the QTL that are involved in the pathways that we see responding to infection Fisher et al 2009. Once the pathways that control the response to infection have been identified, it will be possible to develop better strategies for control of the disease and breed cattle that are innately resistant.

Anaemia is one of the most important features of trypanosomiasis and anaemia rather than parasitaemia is usually used as the indicator of when to treat infected animals. We have used our microarray data from mice that develop different levels of anaemia after infection to explore the mechanisms regulating these differences (Noyes et al 2009).

Trypanosomes are blood stream parasites and consequently the symptoms of the infection are not specifically associated with any organ or cell type. This makes it much harder to identify the genes controlling response to infection because we do not know where to look. We have bred new lines of mice that contain just small regions of the genome of mice that are relatively resistant to infection whilst most of their genome comes from mice that are relatively susceptible to infection. These mice can tell us if the resistance genes are in the regions of the genome from the resistant mice. We have collected a large amount of clinical chemistry data on these mice in collaboration with The German Mouse Clinic to get a better idea of the responses that differentiate susceptible and resistant mice (Rathkolb et al. 2009).

Purpose of this website:

This website has been devised with three principal aims:

References

pdf image and link

Localisation of genes controlling resistance to trypanosomiasis in mice Kemp SJ, Iraqi F, Darvasi A, Soller M & Teale AJ. (1997) Nature Genetics 16:194–197.

pdf image and link Mapping of quantitative trait loci controlling trypanotolerance in a cross of tolerant West African N'Dama and susceptible East African Boran cattle. Hanotte O, Ronin Y, Agaba M, Nilsson P, Gelhaus A, Horstmann R, Sugimoto Y, Kemp S, Gibson J, Korol A, Soller M & Teale A (2003). Proceedings of the National Academy of Sciences 100, 3; 7443–7448.

PDF OF PAPER

A Systematic Strategy for the Discovery of Candidate Genes Responsible for Phenotypic Variation Paul Fisher, Harry Noyes, Stephen Kemp, Robert Stevens & Andrew Brass. Methods in Molecular Biology: Vol 573 Cardiovascular Genomics 2009: 329–345

PDF OF PAPER

Clinical chemistry of mice congenic for QTL for response to Trypanosoma congolense infection. Rathkolb B, Noyes HA, Brass A, Dark P, Fuchs H, Gailus-Durner V, Gibson J, Hrabé de Angelis M, Ogugo M, Iraqi F, Kemp SJ, Naessens J, Pope ME, Wolf E & Agaba M. Infection and Immunity 2009 77:3948–3957

PDF OF PAPER

Mechanisms controlling anaemia in Trypanosoma congolense infected mice. Noyes H., Alimohammadian M., Agaba M., Brass A., Fuchs H., Gailus-Durner V., Hulme H., Iraqi F., Kemp S., Rathkolb B., Wolf E., de Angelis M., Roshandel D., Naessens J. PLoS One. 2009 44:e5170