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

Abstract

Abstract 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.