Dubrova and Co-Workers Explained:
Nuclear Weapons Tests and Human Germline Mutation Rate.
Reference: Dubrova, Y.E., Bersimbaev, R.I., Djansugurova, L.B., Tankimanova, M.K., Mamyrbaeva, Z. Zh., Mustonen, R., Lindholm, C., Hulten, M. and Salomaa, S. (2002) Nuclear Weapons Tests and Human Germline Mutation Rate, Science, 295(5557), p. 1037
What was the research question?
Between 1949 and 1989, the former Soviet Union conducted 470 nuclear tests (surface, atmospheric and underground) at the Semipalatinsk test site in Kazakhstan. The local population was exposed to radioactive fallout, with ~85% of the collective dose being attributed to four surface tests which took place in 1949, 1951, 1953 and 1956. By the time this study was conducted (2002), the dose received by local people from the site was known to be low.
The research team wanted to investigate the genetic risk to local people due to contamination from these nuclear tests; i.e. whether any changes had occurred to the germline (inheritable) DNA of local Kazakhstani people.
How was the scientific problem approached?
The authors chose to focus their study on parts of the human genome called minisatellites; these are small sequences of DNA that are repeated multiple times in DNA. Minisatellites do not code for proteins and whether any health effects are associated with their mutation is a subject of ongoing research.
It is known that minisatellites are more prone to mutation compared to the rest of the human genome and the researchers analysed them for this reason. The authors sought to establish whether there was a higher rate of mutation among the local population compared to a control group.
What did the research involve?
The researchers collected blood samples from 40 three-generation families (grandparents, parents and children) who lived in areas close to Semipalatinsk where doses greater than 1 Sv were known to have been received. They also collected blood samples from a control group made up of 28 non-exposed families, who were matched with respect to ethnicity, year of birth, parental age, occupation and smoking habits. The generations of grandparents, parents and children are referred to as P0, F1 and F2.
The research team analysed the minisatellite regions of DNA in lymphocyte cells (white blood cells) isolated from human blood using 8 different probes; sequences of DNA linked to reporter signals to enable detection. The authors determined the frequency of minisatellite mutations, as a population, for each generation of exposed and control families.
What did they find?
The number of spontaneous mutations in the control group P0 and F1 generations was found to be similar. The number of minisatellite mutations in the exposed P0 group was on average 80% higher than the controls and, the exposed F1 group was on average 50% higher than the controls.
There was much greater variation in the level of mutations in the exposed F1 generation than for the exposed P0 generation. The most important predictor for the relative number of excess minisatellite mutations among the F1 generation is the years that their parents were born in. For both generations, the authors observed that parents exposed during times when contamination was highest showed increased levels of excess minisatellite mutations in their children, as a population.
How did the researchers interpret their results?
The authors considered their findings to be evidence that exposure of a given generation of people to ionising radiation increased the level of excess minisatellite mutations in their children.
Who did this research?
This work was performed by a team of researchers from the University of Leicester, the Kazakh State National University, the Kazakhstan Institute of General Genetics and Cytology, the Finish STUK Radiation and Nuclear Safety Authority and the University of Warwick.
Elevated levels of minisatellite mutations were detected in two generations of family groups living near the Semipalatinsk nuclear test site compared to the control group generations.
The excess levels of minisatellite mutations in each generation correlate with the increased contamination levels of radiation in the locale resided in by their parents.
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