Flal1^PWK/PhJ
QTL Variant Detail

Summary

• QTL variant: Flal1^PWK/PhJ
• Name: fatty liver accumulation QTL 1, females only; PWK/PhJ
• MGI ID: MGI:6209538
• QTL: Flal1 Location: Chr17:8218832-11218887 bp Genetic Position: Chr17, Syntenic

Variant origin

• Strain of Specimen: PWK/PhJ

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:237788

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.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the western world, with spectrum from simple steatosis to non-alcoholic steatohepatitis, which can progress to cirrhosis. NAFLD developments are known to be affected by host genetic background. This study emphasizes the power of Collaborative Cross (CC) mice for dissecting this complex trait and revealing QTL controlling hepatic fat accumulation in mice.

168 female and 338 male mice (18-20 weeks old) from 24 and 37 PreCC#/Tau lines, respectively, were maintained on standard rodent diet since weaning. Hepatic fat content was assessed using dual DEXA scan in the liver.

High molecular genomic DNA of the CC lines were initially genotyped with the mouse diversity array (MDA), which consists of 620,000 SNPs (Yang et al. 2009). After about two 4-generation intervals of inbreeding, all the CC lines were re-genotyped by mouse universal genotype array (MUGA-7500 markers) and finally with MegaMuga (77,800 markers) SNP arrays to confirm their genotype status (Iraqi et al. 2012). Founder genome haplotypes were reconstructed using hidden Markov Model (HMM) HAPPY software (Mott et al. 2000) and QTL mapping was performed using percentage liver fat accumulation as the trait.

QTL mapping results revealed two significant and one suggestive fatty liver accumulation QTL that were specifically mapped in females. No QTL were identified in males.

Significant QTL Flal1 (fatty liver accumulation QTL 1, females only) maps to Chr17:8-11 Mbp with a peak LOD score of 5.618 at SNP JAX00431012.

Significant QTL Flal2 (fatty liver accumulation QTL 2, females only) maps to Chr18:64-66 Mbp with a peak LOD score of 5.58 at SNP JAX00462266.

Suggestive QTL Flal3 (fatty liver accumulation QTL 3, females only) maps to Chr4:35-37 Mbp with a peak LOD score of 5.41 at SNP JAX00548268.

Flal1 and Flal2 showed complex pattern of haplotype effects of the founders, with the wild-derived strains (mainly PWK/PhJ) playing a role, although other strains also contributed to the overall QTL effect.

References

• Original: J:237788 Atamni HJ, et al., Mapping liver fat female-dependent quantitative trait loci in collaborative cross mice. Mamm Genome. 2016 Dec;27(11-12):565-573
• All: 1 reference(s)