A major genetic locus in Trypanosoma brucei is a determinant of host pathology

Morrison, L.J., Tait, A., McLellan, S., Sweeney, L., Turner, C.M.R. and MacLeod, A. (2009) A major genetic locus in Trypanosoma brucei is a determinant of host pathology. PLoS Neglected Tropical Diseases, 3(12), e557. (doi:10.1371/journal.pntd.0000557)

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Abstract

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named <i>TbOrg1</i>). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (<i>TbOrg2</i>). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLeod, Professor Annette and Tait, Professor Andy and Sweeney, Mrs Lindsay and McLellan, Ms Sarah and Morrison, Dr Liam and Turner, Professor Charles
Authors: Morrison, L.J., Tait, A., McLellan, S., Sweeney, L., Turner, C.M.R., and MacLeod, A.
College/School:College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Published Online:01 December 2009
Copyright Holders:Copyright © 2009 The Authors
First Published:First published in PLoS Neglected Tropical Diseases 3(12):e557
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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