Elijah Edmondson elijah.edmondson@gmail.com
This package contains R code optimized for mapping and plotting genome wide association studies in heterogenous stock mice for binary phenotypes, such as neoplasia, and time-to-event data, such as tumor latency, to reveal genomic loci that confer susceptibility or resistance to radiation-associated phenotypes. Significane for each QTL experiment can be calculated utilizing permutation test functions within this package. In addition, this package includes functions that utilize heatmaps generated from multiple QTL to perform hierarchical clustering which seek to reveal potentially conincident loci between different phenotypes within the same radiation exposure groups.
Space travel exposes astronauts to a unique, densely ionizing radiation—HZE ions— however the differential carcinogenicity for this radiation quality is poorly characterized in genetically diverse populations. To date, most radiation carcinogenesis studies have used inbred strains of mice and rats, or stocks with limited genetic heterogeneity. These studies have provided valuable information on the relative biological efficiencies of various radiation qualities, however, the advent of advanced heterogeneous mouse stocks, inexpensive high-throughput single nucleotide polymorphism (SNP) genotyping, and new bioinformatic approaches allows the study of radiation carcinogenesis in genetically diverse populations. These tools allow for fine mapping resolution to determine differential genomic susceptibility loci following exposure to HZE or γ-ray irradiation. Mice were exposed to 240 MeV/n 28Si ions (308 mice) or 600 MeV/n 56Fe ions (314 mice) and results are compared to unirradiated controls (613 mice) and gamma (615 mice) irradiated animals. The accompanying dataset includes informatin from an 800 day carcinogenesis study with 1,850 HS/npt mice of both sexes genotyped for 77,808 SNPs (MegaMUGA, 2013-2014 -- NASA grant NNX12AB54G). Mice were phenotyped for neurobehavioural outcomes, cataractogenesis, and neoplasia. Thorough necropsies were performed on each mouse and all organ systems were evaluated including the central nervouse system, both harderian glands, the skeletal system, and all other organ systems. Histopathology was performed for all abnormalities in all mice by a board certified veterinary pathologist (dACVP). For the attached data, time to event data includes cataractogenesis, tumor latencies, and lifespan. Mice were irradiated or sham irradiated at the NASA Space Radiation Laboratory at Brookhaven National labs. Exposures are as follows:
- HZE ions (622 mice)
- γ-rays (615 mice)
- or unirradiated (613 mice)