Nociq4^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Nociq4^CAST/EiJ
• Name: nociceptive sensitivity QTL 4; CAST/EiJ
• MGI ID: MGI:6446212
• QTL: Nociq4 Location: Chr1:12025069-15142285 bp Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:291141

QTL Reference Notes

The Diversity Outbred heterogeneous stock (J:DO) is a developing mouse population derived from progenitor lines of the Collaborative Cross (CC). The CC is a panel of recombinant inbred (RI) mouse strains that 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 (Churchill et al. 2004). Animals from 160 incipient CC lines at early stages of inbreeding were used to establish the DO population, which is maintained by a randomized outbreeding strategy that avoids brother-sister matings. The DO and CC populations thus capture the same set of natural allelic variants derived from a common set of eight founder strains, with DO mice being outbred and the CC population being inbred. 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.

Chronic pain is a maladaptive condition in which the sensation of pain persists in the absence of ongoing tissue damage. Identification of genetic variants that influence susceptibility to pain is key to identifying molecular mechanisms and targets for effective and safe therapeutic alternatives to opioids. To identify genes and variants associated with persistent pain, the authors measured late-phase response to formalin injection in 275 male and female Diversity Outbred (DO) mice.

Male and female DO mice (n = 300; J:DO, JAX stock number 009376) from generation 8 (G8) of outcrossing were obtained from The Jackson Laboratory at age 11 weeks and tested at age 13 to 17 weeks. A total of 288, 13- to 17-week-old DO mice (147 female and 141 male) were phenotyped using the formalin assay of nociception. Twelve of the original 300 mice were excluded from analysis because of bite wounds or congenital abnormalities, including hind leg splay and cranial malformation.

Genotyping was performed on all 288 DO samples using the MegaMUGA genotyping array. Built on the Illumina Infinium platform (San Diego, CA), the MegaMUGA contains 77.8 K SNP markers distributed throughout the mouse genome with an average spacing of 33 Kb.

QTL mapping was performed in 275 DO mice (147 female and 128 male). Of the 288 phenotyped animals, 3 mice were excluded because of missing genotype calls, and 10 were excluded because of video recording error. Mapping was performed as described by Gatti et al. (2014) using genome coordinates from GRCm38.

One QTL reached genome-wide significance for latephase response to formalin injection:

Nociq4 (nociceptive sensitivity QTL 4) maps to Chr 1: 11.95 - 15.07 Mb (rs246258668 - rs580950795) with a peak LOD score of 5.71 at 14.29 Mb. CAST/EiJ alleles contribute to decreased late phase response to formalin injection at Nociq4.

Trpa1 is given as the most likely candidate genes in the Nociq4 interval.

References

• Original: J:291141 Recla JM, et al., Genetic mapping in Diversity Outbred mice identifies a Trpa1 variant influencing late-phase formalin response. Pain. 2019 Aug;160(8):1740-1753
• All: 1 reference(s)