Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  2
• Reference
  J:85813 Lyons MA, et al., Lith6: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains. J Lipid Res. 2003 Sep;44(9):1763-71
• ID
  MGI:2682399

Genes

Gene	Assay Type
Lith24	resistance/susceptibility
D2Mit94	PCR amplified length variant

Notes

• Experiment
  Linkage analysis was performed on a population of (CAST/Ei x DBA/2J)F2 animals to identify QTLs associated with cholesterol gallstones. Parental strain CAST/Ei is susceptible to gallstone formation whereas parental strain DBA/2 is resistant. Interestingly, (CAST/Ei x DBA/2J)F1 females are completely resistant to gallstone formation whereas F2 males exhibit 100% incidence of cholesterol gallstones. Animals were placed on a lithogenic diet for 8 weeks to promote the gallstone phenotype. CAST/Ei parentals also exhibit increased hepatic bile cholesterol concentration compared to parental strain DBA/2J.
  
  A significant QTL on chromosome 2 was identified that colocalized with the previoulsy identified Lith1 QTL. [Curator note: Because Lith1 was originally mapped using a (AKR/J x C57L/J)F1 x AKR/J backcross (J:66646), we consider the current study a separate mapping experiment and have named the QTL Lith24.] Lith24 mapped to mouse Chromosome 2 at D2Mit94. Lith24 reached significant linkage to gallstone presenceat 52 cM with LOD=3.8 and reached suggestive linkage to aggregated cholesterol monohydrate crystals at 46 cM with LOD=2.8. The QTL range of Lith24 extends from 40 cM - 60 cM on mouse Chromosome 2. DBA/2J-derived alleles confer dominantly inherited susceptibility to cholesterol gallstone formation at Lith24.
  
  A novel QTL named Lith6 was identified in association with aggregated cholesterol monohydrate crystals at 54 cM on mouse Chromosome 6 with LOD=3.8 at D6Mit62. The QTL range of Lith6 extends from 40 cM - 70 cM. CAST/Ei-derived alleles confer dominantly inherited susceptibility to cholesterol gallstone formation at Lith6. Slco1a1 and Pparg are candidate genes for Lith6 and both show differential expression between CAST/Ei and DBA/2J.
  
  Another novel QTL on proximal mouse Chromosome 6 near D6Mit86, Lith10, is linked to gallstone number reaching peak significanceat 4 cM with LOD=3.6. Lith10 is also suggestively linked to gallstone presence at 0 cM with LOD=2.8. The QTL range of Lith10 extends from approximately 0 cM - 10 cM. DBA/2J-derived alleles confer recessively inherited susceptibility to gallstone formationat Lith10.
  
  Lith11 mapped to 58 cM on mouse Chromosome 8 in association with gallstone number. Lith11 reached peak significance at D8Mit88 with LOD=3.3. The QTL range of Lith11 extends from 48 cM - 60 cM. DBA/2J-derived alleles confer recessively inherited susceptibility to gallstone formation at Lith11.