Albq18^A/J
QTL Variant Detail

Summary

• QTL variant: Albq18^A/J
• Name: albuminuria QTL 18; A/J
• MGI ID: MGI:5755804
• QTL: Albq18 Location: unknown Genetic Position: Chr10, Syntenic

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:188618

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 insipient 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 a mapping population of 190 PreCC#/Unc mice. Multiple generations of mice from G2:F5F8 were included in the phenotype population, but only the G2:F7 generation was genotyped using 13,000 SNPs that differentiate the eight founder haplotypes at >1,200 loci. Therefore, genotypes for mice in the G2:F5, G2:F6, and G2:F8 generations were inferred from G2:F7 parents or siblings that were genotyped directly; because the population is 80% inbred, it is possible to determine haplotype of origin with certainty at most locations for most mice using this approach.

The study identified a single novel locus, Albq18, associated with increased susceptibility to albuminuria. Albq18 maps to 8.7 Mb - 13.5 Mb on Chromosome 10, with a peak LOD score of 9.0 at 4.7 cM. All coordinates are relative to mouse genome Build 37.

PreCC#/Unc mice carrying haplotypes from WSB/EiJ and A/J at the Albq18 locus displayed significantly higher albuminuria than mice carrying haplotypes from the other PreCC#/Unc founder strains.

Albq18 contains the mouse ortholog of human SASH1, which is significantly associated with diabetic nephropathy in humans. Murine Sash1 is thus considered a likely candidate gene for the Albq18 QTL.

References

• Original: J:188618 Thaisz J, et al., Genetic analysis of albuminuria in collaborative cross and multiple mouse intercross populations. Am J Physiol Renal Physiol. 2012 Oct;303(7):F972-81
• All: 1 reference(s)