Abstract
Behavioral and cognitive traits have a genetic component even though contributions from individual genes and genomic loci are in many cases modest. Changes in the environment can alter genotype–phenotype relationships. Space travel, which includes exposure to ionizing radiation, constitutes environmental challenges and is expected to induce not only dramatic behavioral and cognitive changes but also has the potential to induce physical DNA damage. In this study, we utilized a genetically heterogeneous mouse model, dense genotype data, and shifting environmental challenges, including ionizing radiation exposure, to explore and quantify the size and stability of the genetic component of fear learning and memory-related measures. Exposure to ionizing radiation and other external stressors altered the genotype–phenotype correlations, although different behavioral and cognitive measures were affected to different extents. Utilizing an integrative genomic approach, we identified pathways and functional ontology categories associated with these behavioral and cognitive measures.
Highlights
A unique feature of the space radiation environment is the presence of galactic cosmic rays (GCRs) and solar particle events (SPEs)
We leveraged the presence of two distinct cohorts and exposure to different types of radiation to detect significant QTL groups, but more importantly to evaluate their reproducibility across cohorts and radiation types
Our work contributes to the understanding of causes of the varying levels of reproducibility affecting QTL studies
Summary
A unique feature of the space radiation environment is the presence of galactic cosmic rays (GCRs) and solar particle events (SPEs). GCR involves protons and fully ionized atomic nuclei such as 56Fe, while SPE includes predominantly low-to-medium energy protons with a small heavy ion component. These exposures pose a significant hazard to space flight crews during the mission and at later times after the mission when slow-developing adverse effects could become apparent. In people exposed to irradiation, the nature and extent of behavioral and cognitive changes is variable and cannot be predicted on the basis of radiation dose and type. This suggests the involvement of genetic factors. Radiation studies typically involved inbred strains of mice and rats, crosses of inbred mice to generate F1 mice, stocks with
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