Experiment
Previously identified QTLs for trypanosome resistance (Tir1, Tir2, Tir3) were further analyzed using congenic line analysis. Donor DNA segments derived from C57BL/6OlaHsd were introgressed onto an A/JOlaHsd genetic background for 5 generations using marker-assisted congenic selection. Parental strain C57BL/6OlaHsd is resistant to infection with Trypanosome congolense whereas parental strain A/JOlaHsd is susceptible. Congenic animals were infected with T. congolense at 9-19 weeks of age and resistance wasmeasured by survival time. It was observed that ortality of infected animals was has two separate phases- and early phase (death before 20 days post-infection) and late phase (death after 20 days post-infection). Unlike in prior studies, a sex effectwas not observed for these Tir1, Tir2 and Tir3.
6.4.2015 Curators Note: Because Tir1, Tir2, and Tir3 were originally mapped in 1996 in J:98907 using a (BALB/cOlaHsd x C57BL/6JOlaHsd)F2 cross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named these QTL Tir4, Tir5, and Tir6 repectively.
Tir4 (trypanosome infection response 4) is located at 18.2 cM on mouse Chromosome 17. The C57BL/6OlaHsd-derived congenic region includes D17Mit29 (15.1 cM), D17Mit16 (17.4 cM) and D17Mit11 (22.8 cM). The trypanosome-resistant phenotype was replicated in this congenic line. The C57BL/6OlaHsd-derived Tir4 locus appears to confer increased survival time (averaging 23.3 days longer survival) with a recessive mode of inheritance in the early phase and a dominant mode of inheritance in the late phase. Tir4 explains 24.3% of the phenotypic variance.
Tir5 (trypanosome infection response 5) is located at 44 cM on mouse Chromosome 5. The C57BL/6OlaHsd-derived congenic region includes D5Mit200 (36 cM), D5Mit113 (42cM) and D5Mit10 (54 cM). The Tir5 locus influences late phase mortality with C57BL/6OlaHsd-derived alleles conferring increased survival time (averaging 26.2 days longer survival) in the late phase with a possibledominant or additive effect. Tir5 explains 21.5% of the phenotypic variance.
Tir6 (trypanosome infection response 6) is located at 81.6 cM on mouse Chromosome 1. The Tir6 congenic line carries C57BL/6OlaHsd-derived DNA encompassing D1Mit87 (62 cM), D1Mit217 (64.1 cM) and D1Mit60 (58.7 cM). This locus confers dominantly-inherited resistance to trypanosome infection in the late phase. Animals infected with T. congolense and homozygous for C57BL/6OlaHsd-derived alleles at Tir6 live an average of 23.8 days longer compared to A/JOlaHsd homozygotes. Tir6 explains 17.6% of the phenotypic variance.
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