Tisms1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Tisms1^C57BL/6J
• Name: tissue mass spleen 1; C57BL/6J
• MGI ID: MGI:5767228
• QTL: Tisms1 Location: unknown Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL

Notes

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

J:153546

Linkage analysis was performed on a mapping population of 384 Glnd:HVWR3 Myh4^minimsc x (Glnd:HVWR3 Myh4^minimsc x C57BL/6)F1 backcross mice to identify genomic loci related to voluntary exercise in mice. Mice were genotyped at 154 informative SNP markers (genome build not given).

The authors previously created a backcross (BC) between mice selectively bred for high levels of voluntary wheel running (VWR) and fixed for "mini muscle" (MM), a recessive mutation causing ~50% reduction in triceps surae mass. They previously showed that BC mice having the MM trait ran faster and further than mice without MM and that MM maps to chromosome 11.

In the present study the authors genotyped the BC with genome-wide SNPs to identify

QTL controlling voluntary exercise and tissue and body mass traits. They also sought to determine whether the identified QTL interact with the MM locus or with sex.

First the authors mapped MM as a binary variable based on nonoverlapping masses of triceps surae muscles. A genome-wide scan for the MM locus produced a single peak centered at 43.37 cM on Chromosome 11 with a peak LOD score of 93.56 at 53.39 cM and a 95% CI between 41.37 and 46.37 cM. This QTL is represented in the MGI database as the protein coding gene Myh4 (myosin, heavy polypeptide 4, skeletal muscle).

To identify QTL controlling VWR and tissue mass traits, the authors initially performed single, additive QTL model genomewide scans with and without MM in the QTL model. Without MM in the model, a QTL peak was detected at the MM locus on Chromosome 11 for all traits except running time, strongly demonstrating the effect of the MM mutation on VWR and tissue mass traits. When MM was included in the model, all Chromosome 11 QTL disappeared as expected. To account for the strong effect of the MM locus, all subsequent QTL scans included MM in the QTL model.

Using the single, additive QTL model, the authors detected 3 significant VWR QTL and 4 significant tissue mass QTL in the BC population:

QTL Vwr1 (voluntary wheel running 1) maps to 42.75 - 60.75 cM on Chromosome 7 with a peak LOD score of 5.9 at 53.39 cM.

QTL Vwr2 (voluntary wheel running 2) maps to 39.72 - 73.0 cM on Chromosome 6 with a peak LOD score of 3.43 at 65.0 cM.

QTL Vwr3 (voluntary wheel running 3) maps to 35.74 - 60.74 cM on Chromosome 7 with a peak LOD score of 4.96 at 53.39 cM.

QTL Tismt (tissue mass triceps) maps to 15.88 - 34.88 cM on Chromosome 17 with a peak LOD score of 2.87 at 21.88 cM.

QTL Tismv (tissue mass ventricle) maps to 63.11 - 93.16 cM on Chromosome 3 with a peak LOD score of 5.98 at 90.11 cM.

QTL Tisms1 (tissue mass spleen 1) maps to 53.0 - 89.0 cM on Chromosome 6 with a peak LOD score of 3.85 at 60.0 cM.

QTL Tisms2 (tissue mass spleen 2) maps to 29.87 - 67.16 cM on Chromosome 13 with a peak LOD score of 4.08 at 55.87 cM.

The authors next sought to identify significant and suggestive interactions between VWR or tissue mass QTL and MM locus or sex. Only the ventricle mass QTL on Chromosome 3 (Tismv) was found to interact significantly with the Myh4 QTL on Chromosome 11 (LOD^Full = 8.97, ^deltaLOD = 2.99), because it significantly affected the ventricle mass trait among MM mice, but had little effect on non-MM mice. The QTL x sex interaction analysis revealed that Myh4 may be influenced by sex, as a highly significant QTL x sex interaction for triceps surae mass was observed on Chromosome 11 within the 95% CI for Myh4.

References

• Original: J:153546 Nehrenberg DL, et al., QTL underlying voluntary exercise in mice: interactions with the "mini muscle" locus and sex. J Hered. 2010 Jan-Feb;101(1):42-53
• All: 1 reference(s)