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Background  Trypanosomosis is the most economically important disease constraint to livestock productivity in Africa. A number of trypanotolerant cattle breeds are found in West Africa, and identification of the genes conferring trypanotolerance could lead to effective means of genetic selection for trypanotolerance. In this context, high resolution mapping in mouse models are a promising approach to identifying the genes associated with trypanotolerance. In previous studies, using F2 C57BL/6J × A/J and C57BL/6J × BALB/cJ mouse resource populations, trypanotolerance QTL were mapped within a large genomic intervals of 20-40 cM to chromosomes MMU17, 5 and 1, and denoted  Tir 1,  Tir 2 and  Tir 3 respectively. Subsequently, using F6 C57BL/6J × A/J and C57BL/6J × BALB/cJ F6 advanced intercross lines (AIL),  Tir 1 was fine mapped to a confidence interval (CI) of less than 1 cM, while  Tir 2 and  Tir 3, were mapped within 5-12 cM.  Tir 1 represents the major trypanotolerance QTL.    Results  In order to improve map resolutions of  Tir 2 and  Tir 3, an F12 C57BL/6J × A/J AIL population fixed for the susceptible alleles at  Tir 1 QTL was generated. An F12 C57BL/6J × A/J AIL population, fixed for the resistant alleles at  Tir 1 QTL was also generated to provide an additional estimate of the gene effect of  Tir 1. The AIL populations homozygous for the resistant and susceptible  Tir 1 alleles and the parental controls were challenged with  T. congolense  and followed for survival times over 180 days. Mice from the two survival extremes of the F12 AIL population fixed for the susceptible alleles at  Tir 1 were genotyped with a dense panel of microsatellite markers spanning the  Tir 2 and  Tir 3 genomic regions and QTL mapping was performed.  Tir 2 was fine mapped to less than 1 cM CI while  Tir 3 was mapped to three intervals named  Tir 3a,  Tir 3b and  Tir 3c with 95% confidence intervals (CI) of 6, 7.2 and 2.2 cM, respectively.    Conclusions  The mapped QTL regions encompass genes that are vital to innate immune response and can be potential candidate genes for the underlying QTL.

bmc genomics

High resolution mapping of trypanosomosis resistance loci Tir 2 and Tir 3 using F12 advanced intercross lines with major locus Tir 1 fixed for the susceptible allele