Bcdr1^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Bcdr1^CAST/EiJ
• Name: benzene-induced chromosome damage in reticulocytes; CAST/EiJ
• MGI ID: MGI:5755729
• QTL: Bcdr1 Location: unknown Genetic Position: Chr10, 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:228640

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 600 male J:DO mice between 5 and 8 weeks of age, obtained from The Jackson Laboratory, Bar Harbor, ME. The mice were received in two cohorts of 300 mice each from the 7th and 8th generation of outbreeding, respectively, which were delivered 4 months apart. The study identified a single novel locus, named Bcdr1, significant for the trait "benzene-induced chromosomal damage in reticulocytes."

The authors exposed two independent cohorts of 300 male J:DO mice to benzene at 0, 1, 10, or 100 ppm and measured micronucleated reticulocytes and erythrocytes, markers of chromosomal damage in red blood cells. Micronucleus (MN) frequency in reticulocytes (RET) and mature erythrocytes (ERC) was used as a quantitative measure of chromosomal damage.

The authors estimated exposure thresholds using benchmark concentration modeling for each cohort separately and for the combined data. They then performed linkage mapping to discover genomic loci that are associated with benzene-induced chromosomal damage in reticulocytes using DO mice in the combined 100-ppm exposure groups.

The authors genotyped each mouse at 7,854 markers (Mouse Universal Genotyping Array, MUGA) and performed linkage mapping on postexposure MNRET in blood and bone marrow using 144 animals with complete data in the combined 100-ppm exposure groups.

Bcdr1 maps to 31.87 - 34.2 Mb on Chromosome 10, with a peak LOD score of 20.7. CAST/EiJ alleles are associated with lower levels of MNRET and act in a dominant fashion. The authors report that mice carrying at least one copy of the CAST/EiJ allele on Chr 10 are more resistant to benzene-induced chromosomal damage.

References

• Original: J:228640 French JE, et al., Diversity Outbred Mice Identify Population-Based Exposure Thresholds and Genetic Factors that Influence Benzene-Induced Genotoxicity. Environ Health Perspect. 2015 Mar;123(3):237-45
• All: 1 reference(s)