Gripgtt2^PWK/PhJ
QTL Variant Detail

Summary

• QTL variant: Gripgtt2^PWK/PhJ
• Name: glucose response to intraperitoneal glucose tolerance test 2, females only; PWK/PhJ
• MGI ID: MGI:6202017
• QTL: Gripgtt2 Location: Chr8:32510028-34987154 bp Genetic Position: Chr8, 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:250368

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.

Type-2 diabetes (T2D) is a complex metabolic disease characterized by impaired glucose tolerance. Despite environmental high risk factors, host genetic background is a strong component of T2D development. Herein, novel highly genetically diverse strains of Collaborative Cross (CC) lines from mice were assessed to map QTL associated with variations of glucose-tolerance response.

In total, 501 mice of 58 CC#/Tau lines were maintained on a high-fat (42% fat) diet for 12 weeks. An intraperitoneal glucose tolerance test (IPGTT) was performed for 180 min.; the values of area under curve for glucose level at zero and 180 min (AUC[0-180]) were measured and used for QTL mapping.

Heritability and coefficient of genetic variance (CVg) were 0.49 and 0.31 for females, while for males, these values 0.34 and 0.22, respectively.

All CC#/Tau lines were genotyped with high-density SNP markers, as previously described (Yang et al. 2009; Iraqi et al. 2012; Vered et al. 2014; Levy et al. 2015; Abu Toamih-Atamni et al. 2016b). The R/HAPPY package was used to identify QTL.

One QTL was identified, significant for female mice only:

QTL Gripgtt2 (glucose response to intraperitoneal glucose tolerance test 2, females only) maps to Chr8:32.02-34.52 Mbp with a maximum LOD score of 5.65.

Gripgtt2 showed a complex pattern of haplotype effects of the founders, with the wild-derived strains (mainly PWK/PhJ) playing a major role on increased AUC values, while NZO/HlLtJ genotype reduces this trait, although other strains also contributed (positive or negative) to the overall QTL effect.

References

• Original: J:250368 Abu-Toamih Atamni HJ, et al., Glucose tolerance female-specific QTL mapped in collaborative cross mice. Mamm Genome. 2017 Feb;28(1-2):20-30
• All: 1 reference(s)