Natural radioactivity and human mitochondrial DNA mutations

@article{Forster2002NaturalRA,
  title={Natural radioactivity and human mitochondrial DNA mutations},
  author={Lucy Forster and Peter Forster and Sabine Lutz-Bonengel and Horst Willkomm and Bernd Brinkmann},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2002},
  volume={99},
  pages={13950 - 13954}
}
Radioactivity is known to induce tumors, chromosome lesions, and minisatellite length mutations, but its effects on the DNA sequence have not previously been studied. A coastal peninsula in Kerala (India) contains the world's highest level of natural radioactivity in a densely populated area, offering an opportunity to characterize radiation-associated DNA mutations. We sampled 248 pedigrees (988 individuals) in the high-radiation peninsula and in nearby low-radiation islands as a control… 

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References

SHOWING 1-10 OF 30 REFERENCES
The mutation rate in the human mtDNA control region.
TLDR
The present study sequenced the mtDNA control region in 272 individuals, who were related by a total of 705 mtDNA transmission events, from 26 large Icelandic pedigrees, and the estimated mutation rate is intermediate among those derived from pedigree-based studies.
Down's syndrome and related abnormalities in an area of high background radiation in coastal Kerala
TLDR
The view that radiation-induced genetic anomalies occur with above average frequency in the population living in the area with high background radiation is supported.
A high observed substitution rate in the human mitochondrial DNA control region
TLDR
The data indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck, and has implications for forensic applications and studies of human evolution.
Mitochondrial genome variation and the origin of modern humans
TLDR
The global mtDNA diversity in humans is described based on analyses of the complete mtDNA sequence of 53 humans of diverse origins, providing a concurrent view on human evolution with respect to the age of modern humans.
Genetic analysis of children of atomic bomb survivors.
TLDR
Six minisatellites and five microsatellites in DNA derived from 100 families including 124 children detected a total of 28 mutations in three minisatellite loci, with no significant differences in the mutation rates between the exposed and the unexposed gametes.
Mitochondrial heteroplasmy among maternally related individuals
TLDR
A common bottleneck size in all individuals from this lineage seems to be very unlikely, consistent with both slow and rapid segregation of mtDNAs between the generations, which would implicate a tight as well as a wide bottleneck.
Evidence from human oocytes for a genetic bottleneck in an mtDNA disease.
TLDR
Oocytes from a patient with Kearn-Sayre syndrome caused by mtDNA rearrangements are examined to present direct evidence that the number of segregating units (n) is three to five orders of magnitude less than thenumber of mitochondria in the human female oocyte.
Heteroplasmy of the human mtDNA control region remains constant during life.
TLDR
Heteroplasmy in the control region of mtDNA seems to be inherited and is not the result of somatic age-related accumulation.
Genetic monitoring of the human population from high-level natural radiation areas of Kerala on the southwest coast of India. II. Incidence of numerical and structural chromosomal aberrations in the lymphocytes of newborns.
TLDR
A striking observation was the presence of rogue cells, the rarely occurring metaphases with a high level of chromosomal damage, which have not been reported previously among newborns, which are comparable between the high-level and normal-level natural radiation areas.
...
...