Exposure to ionising radiation can cause genetic damage and, depending upon the dose of radiation, can increase the risk of various diseases. Recent studies have highlighted changes in genes and pathways related to brain function secondary to radiation exposure.
Consequently, individuals exposed through medical therapy, nuclear disasters and occupation might be subject to such risk. Veterans of the British nuclear testing programme may have been exposed to ionising radiation through their participation at nuclear test sites.
The ongoing GCFT study seeks to examine for evidence of radiation exposure in veterans and, any genetic effect in their offspring.
As part of this GCFT study, Moorhouse et al, carried out whole genome sequence (WGS) analysis on nuclear test family trios (veteran father, child and child’s mother) and compared with a military veteran control family trio group. The results of this work are described in Moorhouse et al (reference below with associated lay summary).
In the study described here, the veteran’s whole genome sequence dataset is utilised for the purpose of examining for genetic variation between the nuclear test and control veteran groups. The focus in this particular study aims to look for any relationship with identified genetic variations and functional impact on the brain.
Specifically, by analysing publicly available WGS (DNA sequence) data of nuclear test and control military veterans as described in Moorhouse et al, our objectives are to:
- examine the WGS data to identify genetic variations
- examine for any relationship between identified genetic variations and previously published gene expression data after radiation exposure
- explore possible links between the genes identified and pathways related to normal and abnormal human brain function
To achieve these objectives, we have developed a WGS data analysis process, termed as a pipeline, which utilises human genome reference data and established genome analysis toolkits to identify common and rare variations in the veteran’s DNA sequence. Overall, we are analysing DNA sequences from 60 samples (30 control and 30 nuclear test veterans), the results from which will form the basis of a future research publication.
The potential outcomes of this research could lead to a better understanding of the potential health risks associated with participation at nuclear test sites. In particular, the identification of new biological pathways associated with identified genes could lead to new research opportunities and a better understanding of the underlying mechanisms of possible radiation-induced health effects.
References
Betlazar, C., Middleton, R.J., Banati, R.B. and Liu, G.-J. (2016). The impact of high and low dose ionising radiation on the central nervous system. Redox Biology, 9, pp.144–156. doi: https://doi.org/10.1016/j.redox.2016.08.002
Lopes, J., Baudin, C., Leuraud, K. et al. Ionizing radiation exposure during adulthood and risk of developing central nervous system tumors: systematic review and meta-analysis. Sci Rep 12, 16209 (2022). https://doi.org/10.1038/s41598-022-20462-7
Moorhouse AJ, Scholze M, Sylvius N, Gillham C, Rake C, Peto J, Anderson R, Dubrova YE. No evidence of increased mutations in the germline of a group of British nuclear test veterans. Sci Rep. 2022 Jul 5;12(1):10830. doi: 10.1038/s41598-022-14999-w. PMID: 35790751; PMCID: PMC9256629.
This work is being undertaken by PhD student Justin Dankwa supervised by Dr Cristina Sisu and Dr Rhona Anderson.
