title: A major genetic locus in Trypanosoma brucei is a determinant of host pathology.
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 TbOrg1). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (TbOrg2). 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.
authors: Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, Glasgow, United Kingdom. lm78y@udcf.gla.ac.uk
authors: Liam J
authors: LJ
authors: Morrison
authors: Andy
authors: A
authors: Tait
authors: Sarah
authors: S
authors: McLellan
authors: Lindsay
authors: L
authors: Sweeney
authors: C Michael R
authors: CM
authors: Turner
authors: Annette
authors: A
authors: MacLeod
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006790:Host-Parasite Interactions; D006801:Humans; D008099:Liver / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D015800:Protozoan Proteins / Q000235:genetics; D040641:Quantitative Trait Loci; D013154:Spleen / Q000473:pathology; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000472:pathogenicity*; D014353:Trypanosomiasis, African / Q000469:parasitology / Q000473:pathology*; D014774:Virulence
chemical_list: D015800:Protozoan Proteins