Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  4
• Reference
  J:169740 Aylor DL, et al., Genetic analysis of complex traits in the emerging Collaborative Cross. Genome Res. 2011 Aug;21(8):1213-22
• ID
  MGI:4943746

Genes

Gene
Bwq21
Asph

Notes

• Reference
  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.
  
  
• Experiment
  Linkage analysis was performed on a mapping population of 184 male PreCC#/Unc mice (220 CC lines from G2:F5 to G2:F12) for the traits white head-spotting, baseline body weight, and liver mRNA expression profile. Each mouse in the experiment was genotyped using a high-density SNP array. Most of the genotyping was completed using "test" arrays. These arrays were developed as an intermediate step in the process of developing the Mouse Diversity array. There are two versions of the test array: A-array and B-array. The A-array includes 294,878 SNP assays, and the B-array contains 287,687 additional SNP assays. The authors determined that 181,752 (A-array) and 180,976 (B-array) SNP assays performed well and targeted loci that are polymorphic among the eight founder strains. There is no overlap between the two arrays, but the genome coverage is complete and uniformly distributed in both. In some cases, animals from the same phenotyping arm were genotyped with different arrays. Integration was achieved by merging the two sets and using an HMM to impute haplotypes at loci with missing genotypes. All coordinates are relative to NCBI GRCm37 (mm9).
  
  QTL Whq is significant for the trait "white head-spotting" and maps to 88.6 - 101.3 Mb on Chromosome 10. Association mapping with a marker-based model gives a peak LOD score of 15.78 at 89.9 Mb; using an 8-allele model gives a peak LOD score of 17.36 at 92 Mb. The white head-spotting trait is present in WSB/EiJ in CC founders, suggesting that WSB/EiJ contributes the allele for white head-spotting in the PreCC#/Unc mapping population. The protein coding gene Kitl is a strong candidate gene for the Whq locus.
  
  QTL Bwq21 is significant for the trait "baseline body weight" and maps to 3.03 - 10.34 Mb on Chromosome 4. Association mapping with an 8-allele model gives a peak LOD score of 7.9. The high body weight allele underlying Bwq21 is shared by the NZO/HlLtJ and C57BL/6J strains, the two CC founder strains with the highest body weights. Opposite alleles (for low body weight) are A/J and NOD/LtJ. Asph is reported as the most likely candidate gene.
  
  Curator note: Bwq21 was originially named Bwq14 by the authors. Bwq14 currently references a body weight QTL described in another paper (J:172295). Although Bwq14 and Bwq21 possibly refer to the same locus, our curatorial procedure defines QTL by strain and phenotype measured. Both studies used PreCC#/Unc mice to identify loci significant for body weight; however they used different numbers of CC lines and reported different alleles. We therefore separated these two QTL, leaving one as Bwq14 and renaming the other as Bwq21.