Experiment
This study analyzed the genetic control of T.b.brucei resistance using the recombinant congenic (RC) strains of the BALB/c-c-STS/Dem (CcS/Dem) series. The series comprises 20 homozygous strains derived from the inbred strain BALB/c, the background strain, and the inbred STS/A strain, the donor strain. Each CcS/Dem strain contains a different random subset of approximately 12.5% genes of the donor strain, STS/A and approximately 87.5%
genes of the background strain BALB/c. The CcS/Dem strain was in 38 generations of inbreeding when used for this experiment.
Although the BALB/c and STS/A strains were similarly susceptible to T.b.brucei infection, the recombinant congenic strain CcS11 was more susceptible than either. 169 (CcS11 x BALB/c)F2 hybrids, comprised of 85 females and 84 males, were tested simultaneously as a single experimental group. The differential STS-derived segments of the CcS11 mice were genotyped in the F2 hybrid mice; statistical analysis of linkage revealed four loci, Tbbr1-4, that influence survival time after T.b.brucei infection.
Tbbr1, Trypanosoma brucei brucei response 1, was identified linked to D3Mit45 on Chr 3, CcS11/Dem. Tbbr1 was a significant, main effects, locus in female mice, corrected p=0.049. Female mice homozygous with the STS/A allele (SS) at Tbbr1 survived 4 days longer than those homozygous with the BALB/c (CC) allele at this locus. [Table 1]
Tbbr1 was localized to the distal portion of Chr 3. Potential candidate genes were Ptgfr and Ptger3, as prostaglandins play a suppressive role in infection with African trypanosomes.
A suggestive locus, also linked with survival, was observed at D8Mit85, corrected p=0.054 for females; corrected p=0.0995 in both sexes. Heterozygotes had the shorter survival times. [Table 1.]
Tbbr2, Trypanosoma brucei brucei response 2, was identified linked with D12Mit37 on Chr 12, CcS11/Dem. Tbbr2 was also a main effects QTL, significant in female mice, corrected p=0.022. Female mice homozygous with the STS/A allele (SS) at Tbbr2 survived about 3 days shorter than those homozygous for the BALB/c (CC) allele. [Table 1.]
Tbrr2 was fine mapped to 2.15 Mb segment containing 26 genes [Table 3] however, there was no obvious candidate gene.
Tbbr3, linked with marker D7Mit282, influences survival in interaction with Tbbr4 linked with D19Mit51, corrected p=0.033 in females, corrected p=0.043 in both sexes.
F2 mice with homozygous BALB/c (CC) alleles at Tbbr3 and STS/A (SS) alleles at Tbbr4 or
homozygous STS/S (SS) alleles at Tbbr3 and homozygous BALB/c (CC) alleles at Tbbr4 have a shorter survival time after infection in comparison with other possible allelic combinations at these 2 loci. [Table 2.]
Tbbr3 on Chr 7 and Tbbr4 on Chr 19 map near genes Cd19 and Cd5 respectively. These genes code markers of B lymphocytes.
A suggestive locus was also identified in females in interaction between D8Mit85 and D19Mit60, corrected p=0.055. Shorter survival time was observed in heterozygotes at both markers.
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