Yeager M, et al., (2021) Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident. Science 372 (6543), 725-729.
Here we present a lay summary of a recently published study by Yeager and co-authors. The summary outlines the key research questions, how the researchers went about addressing those questions and, the key findings of the work. You can access more lay summaries and find supporting information on our website Knowledge Hub – Centre for Health Effects of Radiological and Chemical Agents (chrc4veterans.uk).
What were the research questions?
The researchers were interested in a unique form of inherited DNA variation, which arises due to random DNA mutations in the sperm (father) or oocytes (mother) cells. The detection of these newly arising, or de novo, mutations (DNM) has only recently become possible by whole genome sequence techniques. It is thought that between 50 and 100 de novo mutations arise in each person between each generation. The age of the father at the time of conception is known to increase this number and, although damaging agents such as ionising radiation will increase the mutation rate in all exposed cells, increased levels of newly arising DNMs in the children of exposed parents has yet to be observed in studies carried out to date.
The research team wanted to find out if the children of parents exposed to ionising radiation from the 1986 Chernobyl accident had increased levels of DNMs which could be associated with the radiation dose received by their parents. The authors also sought to identify different patterns, or types, of DNM previously identified as being associated with radiation exposure.
How was the scientific problem approached?
The scientists took blood samples from parents who were known to have been exposed either in their role as clean-up workers or, as residents within a defined zone of the Chernobyl site. Estimates of the dose received was available for all those recruited into the study. Newly arising mutations in the children were identified by comparing their DNA with that of their parents.
What did the research involve?
The group being studied was composed of 130 adult children from 105 mother-father pairs, where at least one parent was exposed to radiation as a result of the accident. No control group was included in this study; however, the authors did compare their observations to control populations which have been published elsewhere.
DNA from the blood of each participant was analysed using a technique called Illumina paired-end whole genome sequencing. This technique enables the amount of newly arising mutations and, the type of mutations, to be detected at a high resolution.
Additional techniques were also carried out including measuring the length of telomeres in blood cells (special structures on the ends of chromosomes) of adult children. Telomere length is known to decrease as people get older. Telomere length is also thought to be a useful measure of general health.
What did they find?
The authors found no evidence for any increase in newly arising mutations (or DNM) in the children of Chernobyl exposed parents. Specifically, they report no evidence of a relationship between the total number of DNMs and the dose of radiation estimated to have been received by either, or both, of their parents. They also found no evidence that any individual type of DNMs was associated with parental radiation dose and instead show that the amount and type of DNM was comparable to that reported in the general population. They make an estimate that, at most, less than one newly arising mutation may arise per 100 mGy (0.1 Gy) of paternal or maternal exposure. They did however observe, as expected, an increase in DNMs with increasing age of the parents at the time of conception.
The results for the telomere length measurements found that older (adult) children had shorter telomere lengths, as expected and, that a possible association did exist between radiation exposure in the mother and reduced telomere length in their adult child, although this was not seen in children whose fathers were exposed.
How did the researchers interpret their results?
The main message from the authors is that their study does not provide support for any transgenerational effect of ionizing radiation on germline DNA in humans. They make the point that this is reassuring to families, however, highlight that further work is necessary to understand if higher doses delivered in a single exposure closer to the time of conception, rather than chronic, lower doses over time as received by those in this study, similarly show no increase in DNMs.
They also highlight that the technique used enables high levels of detection of DNA mutations, meaning that if such effects on the human germline DNA do occur, they are either uncommon or, occur at levels which are not detectable.
Who did this research?
This work was done by an international team of researchers from Institutions in the USA; National Cancer Institute, Frederick National Laboratory for Cancer Research, SymbioSeq, American Museum of Natural History, Broad Institute of Harvard and Massachusetts Institute of Technology, Massachusetts General Hospital and Harvard Medical School., Taiwan; Academia Sinica., Brazil; University of Sao Paulo., Ukraine; National Research Centre for Radiation Medicine., Japan; Radiation Effects Research Foundation., Russia; Burnasyan Federal Medical and Biophysical Centre.
• No evidence for any increase in the amount, or type, of newly arising DNA mutations in the children of Chernobyl exposed parents
• The amount and type of DNM is comparable to those reported in the general population
• The study does not provide support for any transgenerational effect of ionizing radiation on germline DNA in humans.
Yeager M, Machiela MJ, Kothiyal P, Dean M, Bodelon C, Suman S, Wang M, Mirabello L, Nelson CW, Zhou W, Palmer C, Ballew B, Colli L, Freedman ND, Dagnall C, Hutchinson A, Vij V, Maruvka Y, Hatch M, Illienko I, Belayev Y, Nakamura N, Chumak V, Bakhanova E, Belyi D, Kryuchkov V, Golovanov I, Gudzenko N, Cahoon EK, Albert P, Drozdovitch V, Little MP, Mabuchi K, Stewart C, Getz G, Bazyka D, Berrington A, Chanock SJ. (2021) Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident. Science 372 (6543), 725-729.