Tcq10^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Tcq10^CAST/EiJ
• Name: total cholesterol QTL 10, after dietary treatment; CAST/EiJ
• MGI ID: MGI:5766380
• QTL: Tcq10 Location: unknown Genetic Position: Chr9, Syntenic

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:229082

QTL Reference Notes

The Diversity Outbred heterogeneous stock (J:DO) is a developing mouse population derived from progenitor lines of the Collaborative Cross (CC). The CC is a panel of recombinant inbred (RI) mouse strains that combines the genomes of eight genetically diverse founder strains - A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ - to capture nearly 90% of the known variation present in laboratory mice (Churchill et al. 2004). Animals from 160 incipient CC lines at early stages of inbreeding were used to establish the DO population, which is maintained by a randomized outbreeding strategy that avoids brother-sister matings. The DO and CC populations thus capture the same set of natural allelic variants derived from a common set of eight founder strains, with DO mice being outbred and the CC population being inbred. Each CC inbred strain represents a fixed and reproducible genotype; each DO animal is a unique, non-reproducible individual with an effectively limitless combination of segregating alleles. CTC (2004), Churchill, G. A., et al.. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet. 36, 1133-7.

The authors used a DO mouse population fed an HFCA diet to identify an A/J-specific isoform of Apobec1 that contributes to atherosclerosis. Linkage analysis was performed on a mapping population of 292 female J:DO mice (G11) to identify loci related atherosclerosis. SNP genotyping was performed utilizing the Mega Mouse Universal Genotyping Array (MegaMUGA), an Illumina Infinium Platform array with 77,800 SNP markers. All coordinates are relative to GRCm38.

Experimental design:

Mice obtained from the Jackson Laboratory were fed a chow diet of variable composition before arriving at the University of North Carolina Mouse Facilities at 4 wk of age. Mice were transferred to a controlled synthetic diet from 4 to 6 wk of age (AIN-76A). At 6 wk of age, clinical markers of cardiovascular disease were measured, and baseline QTL mapping was performed. The mice were then transferred to one of two diet groups such that one sibling of each sib pair was randomly assigned to either the high-fat, cholic acid diet group designed to induce atherosclerosis or the high-protein diet group, expected to be nonatherogenic. QTL mapping was then performed in 24-wk-old mice after diet exposure. Quantification of atherosclerotic lesions was performed in the mice at 24 wk of age.

QTL Tglq7 is significant for the trait "baseline triglyceride level." It maps to 50.2 - 51.6 Mb on Chromosome 9 with a peak LOD score of 11.3 at 51.4 Mb. DO mice carrying the CAST/EiJ allele at the Tglq7 QTL have greater triglyceride levels than those that do not. Tglq7 intersects the previously identified triglyceride level QTL Trigq1 harboring candidate gene ApoA5.

QTL Tcq10 is significant for the trait "after-diet total plasma cholesterol." It maps to 47.84 - 70.04 Mb on Chromosome 9 with a peak LOD score of 7.54 at 48.3 Mb. The CAST/EiJ founder haplotype was associated with high levels of cholesterol. Tcq10 intersects the previously identified cholesterol QTL Cq4 harboring candidate gene ApoA4.

QTL Athsq4 is significant for the trait "atherosclerosis susceptibility." It maps to 122.6 - 122.7 Mb on Chromosome 6 with a peak LOD score of 10.7 at SNP marker UNC11996440. The authors found that DO mice containing the A/J allele at the Athsq4 locus had larger aortic lesions. Apobec1 is reported as the candidate gene. A/J specifically expresses a long isoform of Apobec1, which is induced in response to a HFCA diet. Athsq4 intersects the previously reported atherosclerosis QTL Ath37.

References

• Original: J:229082 Smallwood TL, et al., High-resolution genetic mapping in the diversity outbred mouse population identifies Apobec1 as a candidate gene for atherosclerosis. G3 (Bethesda). 2014 Dec;4(12):2353-63
• All: 1 reference(s)