A System Genetics Approach to Low-Dose Radiation Research

Co-Principal Investigator:
Michael A. Langston, Department of Electrical Engineering and Computer Science, University of Tennessee
Abstract:
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.
Research Partners:
The PI for this project is Brynn H. Voy, formerly at Oak Ridge National Laboratory.
The other Co-PI is Elissa J. Chesler at The Jackson Laboratory.
Relevant Site of Interest:
Low Dose Radiation Research