Tir2^{C57BL/6JOlaHsd}
QTL Variant Detail

Summary

• QTL variant: Tir2^{C57BL/6JOlaHsd}
• Name: trypanosome infection response 2; C57BL/6JOlaHsd
• MGI ID: MGI:3042256
• QTL: Tir2 Location: unknown Genetic Position: Chr5, cM position of peak correlated region/allele: 42.62 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6JOlaHsd

Variant description

• Allele Type: QTL
• Inheritance: Other (see notes)

Notes

This allele exhibits dominant 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 may have a dominant or additive mode of inheritance during the late phase of infection in congenic animals (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:98907

Linkage analysis was performed on 400 (BALB/cOlaHsd x C57BL/6JOlaHsd)F2 animals to identify QTL associated with resistance/susceptibility to trypanosomiasis. F2 animals were innoculated with T.congolense at 10-12 weeks of age. Parental strain BALB/cOlaHsdis susceptible to infection by T.congolense whereas parental strain C57BL/6JOlaHsd is resistant. 90 polymorphic markers were initially screened in a subset of F2 animals in the extreme 5% phenotype range. Subsequently the screen was expanded to F2 animals in the extreme 16% phenotype range using 120 polymorphic markers. The 3 loci that were identified together account for 32% of the variance.

Significant linkage to survival time mapped to a broad region of mouse Chromosome 17 (LOD=11). This locus is named Tir1 (trypanosome infection response 1). A two locus model yields a higher LOD score (LOD=15.1). Tir1 exhibits additive inheritance and explains 18% of the variance. The H2 locus maps to this region.

Significant linkage to survival time mapped to mouse Chromosome 5 with LOD=4. This locus is named Tir2 (trypanosome infection response 2). Tir2 explains 6.1% of the variance. No known candidate genes have been identified for this QTL.

Significant linkage to survival time mapped to mouse Chromosome 1 withLOD=5. This locus is named Tir3 (trypanosome infection response 3). Resistance to T.congolense shows dominant inheritance at Tir3. This QTL explains 10% of the variance. No known candidate genes have been identified for this QTL.

J:66474

Four backcross populations [(C57BL/6JOlaHsd x BALB/cOlaHsd)F1 x BALB/cOlaHsd, BALB/cOlaHsd x (C57BL/6JOlaHsd x BALB/cOlaHsd)F1, (BALB/cOlaHsd x C57BL/6JolaHsd)F1 x BALB/cOlaHsd, and BALB/cOlaHsd x (C57BL/6JOlaHsd x BALB/cOlaHsd)F1] were used to assess the effect of imprinting at loci involved in trypanosomiasis survival (Tir1, Tir2, and Tir3).

Tir1 showed significant linkage for trypanosomiasis survival time with parent of origin at D17Mit16 (LOD = 5.9). Animals from BALB/cOlaHsd fathers and (C57BL/6JOlaHsd x BALB/cOlaHsd)F1 or (C57BL/6JOlaHsd x BALB/cOlaHsd)F1 mothers exhibited higher survival rates than animals from (C57BL/6JOlaHsd x BALB/cOlaHsd)F1 or (C57BL/6JOlaHsd x BALB/cOlaHsd)F1 fathers and BALB/cOlaHsd mothers. Authors speculate that genomic imprinting may play a role in trypanosomiasis survival at Tir1.

Tir3 showed suggestive linkage for trypanosomiasis survival time and parent of origin at D1Mit102 (LOD = 2.2-2.8), and Tir2 was not detected for linkage to survival time and parent of origin.

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: 2 reference(s)