This low dose radiation research project addresses the response to
radiation as a complex trait through the use of a systems genetics
framework. This approach is made possible by the integration of
genetic reference populations, genome sequence, and analytical tools
that have emerged in recent years. Systems genetics is a discovery-based,
forward genetics paradigm that provides the potential for a new set
of discoveries about low dose effects that are not readily attainable
through other strategies. Specifically, it allows for simultaneous
relation of radiation-response phenotypes to the underlying molecular
networks while highlighting regions of the genome that confer altered
sensitivity to radiation exposure. Because the approach is executed
in the context of a population-based model, it provides a robust
picture of radiation effects that occur in the context of natural
genetic variation. We use two powerful genetic reference populations
of mice for these studies: (1) BXD (C57BL/6J X DBA/2J) RI strain panel,
and (2) the Collaborative Cross, an emerging population of mice that
contains a level of genetic and phenotypic diversity on par with the
human population. Our proposed tasks integrate biological emphasis
on the immunological effects of low dose radiation with development
and enhancement of computational and bioinformatic tools that will
accelerate low dose discoveries from multiple data types including
large scale ‘omics datasets. We include a pilot study to begin new
exploration into neurobiological impacts of low dose exposure.
Moreover, we will create a tissue bank that can be mined by other
investigators in the low dose community, which will enable us to
realize the full, integrative power of systems genetics.
Collectively, this project will advance the field of low dose
radiobiology by uncovering multilevel networks that link genetic
variants to radiation response outcomes in a population-based model
system.
