Tir4^{C57BL/6JOlaHsd}
QTL Variant Detail

Summary

• QTL variant: Tir4^{C57BL/6JOlaHsd}
• Name: trypanosome infection response 4; C57BL/6JOlaHsd
• MGI ID: MGI:2445530
• QTL: Tir4 Location: unknown Genetic Position: Chr17, Syntenic

Variant origin

• Strain of Specimen: C57BL/6JOlaHsd

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers resistance to infection by Trypanosome congolense compared to A/JOlaHsd and BALB/cOlaHsd. This allele confers increased survival tim after infection with T. congolense compared to A/JOlaHsd. (J:135428)
• Inheritance: Other (see notes)

Notes

This allele exhibits additive inheritance in the (BALB/cOlaHsd x C57BL/6JOlaHsd)F2 cross and recessive inheritance in the (A/JOlaHsd x C57BL/6JOlaHsd)F2 cross from J:40771. This allele displays recessive inheritance during the early phase of infection and dominant inheritance during the late phase of infection (J:135428).

Mapping and Phenotype information for this QTL, its variants and associated markers

J:40771

A significant variation in the susceptibility of tryponosomiasis in inbred strains of mice enabled the quantitative analysis (QTL) of the trait in genetic crosses. The C57BL/6 strain is relatively resistant compared to the more susceptible strains BALB/cand A/J.

Linkage analysis was performed on F2 mice from both a (BALB/cOlaHsd x C57BL/6JOlaHsd)F2 cross and an (A/JOlaHsd x C57BL/6JOlaHsd)F2 cross. Genotyping was performed on mice with long and those with short survival times selecting for informative microsatellite markers providing coverage of all 19 autosomes and the X chromosome.

Analysis of the (BALB/cOlaHsd x C57BL/6JOlaHsd)F2 cross revealed 3 regions with significant LOD scores.

QTL Tir1 mapped to a region of Chromosome 17 between flanking markers D17Mit135 and D17Mit7 with a LOD score of 11.0 [Fig.1]. Tir1 had an additive effect on survival time and accounted for 14.6% of the variation. D17Mit36 mapped nearest the peak LOD score.

QTL Tir2 mapped to a region of Chromosome 5 between flankingmarkers D5Mit233 and D5Mit10 with a LOD score of 4.6 [Fig.1]. Tir2 also had a significant association with survival time with the resistance allele found to be fully dominant, accounting for 6.7% of the variation. D5Mit58 mapped nearest the peak LOD score.

QTL Tir3 mapped to a region of Chromosome 1 between flanking markers D1Nds2 and D1Mit17 with a LOD score of 5.7 [Fig.1]. This QTL had a additive effect and accounted for 8.9% of the variation. D1Mit425 mapped nearest the peak LOD score.

Analysis of the(A/JOlaHsd x C57BL/6JOlaHsd)F2 cross revealed 2 regions with significant LOD scores on both Chromosome 17 and Chromosome 5. The positions of both QTL appeared to be close to those mapped in (BALB/cOlaHsd x C57BL/6JOlaHsd)F2 cross.

5.27.2015 - Curators Note. Because the second cross here differs from the first we regard the second cross as a separate mapping experiment have have assigned the QTL identified on Chromosomes 17 and 5 with unique identifiers.

In the (A/JOlaHsd x C57BL/6JOlaHsd)F2 cross QTL Tir4 mapped to a region of Chromosome 17 flanked by markers D17Mit28 and D17Mit68 with a LOD score of 9.3 [Fig.1]. Tir4 accounted for 9% of the total variance. D17Mit52 mapped nearest the peak LOD score. The resistance allele was recessive.

In the same cross QTL Tir5 mapped to a region of Chromosme 5 between flanking markers D5Mit255 and D5Mit24 with a LOD score of 3.6 [Fig.1]. Tir5 accounted for 3.9% of the variance and the resistance allele was recessive.

A QTL on Chromosome 1 in the (A/JOlaHsd x C57BL/6JOlaHsd)F2 cross did not acheive significance.

J:63779

A further refined mapping for loci responsible for trypanosomiasis resistance in mice was achieved using advanced intercross lines. Advanced intercross lines were constructed by breeding the progeny from resistant C57BL/6JOlaHsd mice with susceptible mice from both the A/JOlaHsd and the BALBc/OlaHsd strains respectively. Phenotyping, genotyping, and linkage analysis was performed on the G6 progeny designated (B/B6)G6 and (A/B6)G6.

Table 1:

Chromosome 17

In the BALBc/OlaHsd x C57BL/6JOlaHsd G6, (B/B6)G6, population of 892 mice a previoulsy indentified QTL, Tir1 [J:40771], mapped to mouse Chromosome 17 at 18.2 cM nearest marker D17Mit16 (LOD 20.08). The 95% confidence interval was refined to 2.8 cM.

In the A/JOlaHsd x C57BL/6JOlaHsd G6, (A/B6)G6, population of 1986 mice a previoulsy identified QTL, Tir4 [J:40771] mapped to 17.9 cM nearest marker D17Mit175, (LOD 19.35). The 95% confidence interval was refined to 1.3 cM.

Analysis of the combined G6 populations provided an association nearest marker D17Mit16 (LOD 37.56). The 95% confidence interval in the combined data was refined further to 0.9 cM.

Chromosome 5

On mouse Chromosome 5 in the A/JOlaHsd x C57BL/6JOlaHsd G6 population a previously identified QTL, Tir5 [J:40771], mappped to 42.0 cM nearest marker D5Mit113 (LOD 4.63). The 95% confidence interval spanned 16 cM.

In the BALBc/OlaHsd x C57BL/6JOlaHsd G6 population, the previously identified Tir2 QTL identified on Chromosome 5 using the same strains [J:40771] did not acheive significance.

When the data from both Chromosome 5 G6 poulations was combined a peak was detected near D5Mit114 with a LOD score of 5.46 and a 95% confidence interval spanning 12 cM.

Chromosome 1

The Tir3 QTL previoulsy identified in J:98907 using an F2 cross, of the same strains used here, was resolved into 3 distinct QTL in the BALBc/OlaHsd x C57BL/6JOlaHsd G6 population.

Tir3a mapped to 60.0 cM nearest marker D1Mit87 with a LOD score of 4.15 and a 95% confidence interval spanning 9cM.

Tir3b mapped to 74.0 cM nearest markers D1Mit286 and D1Mit268 with a LOD score of 5.88 and a 95% confidence interval spanning 11 cM.

Tir3c mapped to 92.0 cM nearest marker D1Mit113 with a LOD score of 3.78 and a 95% confidence interval spanning 9.0 cM.

5.28.2015 Curators Note - The 3distinct QTL mapped on Chromosome 1 using the A/JOlaHsd x C57BL/6JOlaHsd G6 population represent 3 unique QTL not previously mapped using these strains. We consider this a separate mapping experiment and have named the larger QTL region Tir6 spanning a region for 62.5-96.0 cM encompassing Tir6a, Tir6b and Tir6c [Table 1.].

Tir6a mapped to 62.5 cM nearest marker D1Nds2 with a LOD score of 8.07 and a 95% confidence interval of 0.7 cM.

Tir6b mapped to 70.0 cM nearest markers D1Mit286 and D1Mit102 with a LODscore of 6.8 and a 95% confidence interval spanning 16 cM.

Tir6c mapped to 96.0cM nearest D1Mit16 with a LOD score of 5.49 and a 95% confidence interval spanning 18 cM.

Combining the data from the differing G6 populations for Tir3a and Tir6a resulted in a LOD score of 9.94 nearest D1Nds2 with a 95% confidence interval of 1.8 cM.

Combining the data from the differing G6 populations for Tir3b and Tir6b resulted in a LODscore of 11.3 nearest markers D1Mit286 and D1Mit102 with a 95% confidence interval spanning 10 cM.

Combining the data from the differing G6 populations for Tir3c and Tir6c resulted in a LOD score of 7.62 nearest D1Mit113 with a 95% confidence interval of 8 cM.

References

• Original: J:40771 Kemp SJ, et al., Localization of genes controlling resistance to trypanosomiasis in mice. Nat Genet. 1997 Jun;16(2):194-6
• All: 7 reference(s)