Ccc4^CC011/Unc
QTL Variant Detail

Summary

• QTL variant: Ccc4^CC011/Unc
• Name: colitis susceptibility in the Collaborative Cross 4; CC011/Unc
• MGI ID: MGI:5749410
• QTL: Ccc4 Location: Chr8:65174237-78002730 bp Genetic Position: Chr8, Syntenic

Variant origin

• Strain of Specimen: CC011/Unc

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:216860

QTL Reference Notes

The Collaborative Cross (CC) is a large (~1,000 line) panel of recombinant inbred (RI) mouse strains being developed through a community effort (Churchill et al. 2004). The CC 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. CC strains are derived using a unique funnel breeding scheme. Once inbred, the RI CC lines can be used to generate thousands of potential 'outbred' but completely reproducible genomes through the generation of recombinant inbred crosses (RIX). The designation 'PreCC' is used to describe a mapping population of CC mice that is still at incipient stages of inbreeding. 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.

Linkage analysis was performed on 257 ((CC011/Unc x C57BL/6J) x CC011/Unc) N2 mice using 1059 SNP markers to identify QTL associated with colitis.

QTL Ccc1 maps to 94.8 - 112.3 Mb on Chromosome 12 (Build 37), with the peak LOD score (not given) located at 110.8 Mb. Homozygosity for the CC011/Unc allele at Ccc1 is associated with higher colitis scores, while heterozygosity is associated with lower colitis scores. At the Ccc1 locus, the CC011/Unc inbred line has a recombinant haplotype with a PWK/PhJ haplotype proximally and a NOD/ShiLtJ haplotype distally.

QTL Ccc2 maps to 60.3 - 94.3 Mb on Chromosome 14 (Build 37), with the peak LOD score (not given) located at 64.5 Mb. Homozygosity for the CC011/Unc allele is associated with higher colitis scores, while heterozygosity is associated with lower colitis scores. Ccc2 is driven by the 129S1/SvImJ haplotype of the CC011/Unc allele.

QTL Ccc3 maps to 3.6 - 197.2 Mb on Chromosome 1 (Build 37), with the peak LOD score (not given) located at 162.5 Mb. Ccc3 is driven by the WSB/EiJ haplotype of the CC011/Unc allele.

The authors tested whether inheritance of either one of the two haplotypes segregating at each of the four regions of residual heterozygosity in the M001 male (on chromosomes 8, 14, 17 and 18, see Fig. 2 of manuscript) is associated with colitis. The analysis identified a fourth locus on chromosome 8, Ccc4, associated with colitis in CC011/Unc.

QTL Ccc4 maps to 67.2 - 79.8 Mb on Chromosome 8 (Build 37), with the peak LOD score (not given) located at 70.5 Mb. Heterozygosity for the CAST/EiJ and 129S1/SvImJ alleles at Ccc4 is associated with higher colitis scores, while neither allele has a detectable effect in homozygosity.

Ccc1 and Ccc2 are additive and were identified using a single-locus scan.

Ccc3 was identified using a two-locus scan. Ccc3 and Ccc2 appear to act epistatically with Ccc1.

At Ccc1, Ccc2, and Ccc3, there was a significant association of the CC011/Unc allele in homozygosity with higher colitis scores.

References

• Original: J:216860 Rogala AR, et al., The Collaborative Cross as a resource for modeling human disease: CC011/Unc, a new mouse model for spontaneous colitis. Mamm Genome. 2014 Apr;25(3-4):95-108
• All: 1 reference(s)