Mutation induction in the mouse and human germline

Dubrova, Yu. E.

doi:10.1134/s1022795416010038

Cited by 6 publications

(3 citation statements)

References 77 publications

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“…Many prior studies have indicated that 4 Gy of gamma rays leads to approximately 160 double-stranded DNA breaks, more than 500 clustered lesions, and more than 10,000 other instances of DNA damage (single-strand breaks and base damage) in the mammalian genome 2,26 . The fact that the number of mutations detected in these There is no strain difference of the sequences between B6 and C3H where multisite mutations were occurred.…”

Section: Discussionmentioning

confidence: 99%

“…IR induces various types of DNA damage ranging from nucleotide modifications to DNA strand breaks. Among the DNA damage induced by IR in germ cells, those that are not correctly repaired will lead to de novo mutations in the genomes of offspring 2 . The types and extent of mutations induced by IR in the mammalian germline have been a particularly important issue in the field of radiation biology.…”

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confidence: 99%

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Characteristics of induced mutations in offspring derived from irradiated mouse spermatogonia and mature oocytes

Satoh¹,

Asakawa²,

Nishimura³

et al. 2020

Sci Rep

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The exposure of germ cells to radiation introduces mutations in the genomes of offspring, and a previous whole-genome sequencing study indicated that the irradiation of mouse sperm induces insertions/deletions (indels) and multisite mutations (clustered single nucleotide variants and indels). However, the current knowledge on the mutation spectra is limited, and the effects of radiation exposure on germ cells at stages other than the sperm stage remain unknown. Here, we performed whole-genome sequencing experiments to investigate the exposure of spermatogonia and mature oocytes. We compared de novo mutations in a total of 24 F1 mice conceived before and after the irradiation of their parents. The results indicated that radiation exposure, 4 Gy of gamma rays, induced 9.6 indels and 2.5 multisite mutations in spermatogonia and 4.7 indels and 3.1 multisite mutations in mature oocytes in the autosomal regions of each F1 individual. Notably, we found two types of deletions, namely, small deletions (mainly 1~12 nucleotides) in non-repeat sequences, many of which showed microhomology at the breakpoint junction, and single-nucleotide deletions in mononucleotide repeat sequences. The results suggest that these deletions and multisite mutations could be a typical signature of mutations induced by parental irradiation in mammals.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Characteristics of induced mutations in offspring derived from irradiated mouse spermatogonia and mature oocytes

Satoh¹,

Asakawa²,

Nishimura³

et al. 2020

Sci Rep

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show abstract

“…Increasing evidence suggests that the paternal germline DNMs are associated with various congenital disorders, schizophrenia, autism and reproduction defects 1,9,10 . The correlation between parental exposure to ionizing radiation and genetic effects in the progeny has nonetheless remained uncertain [11][12][13] . Contradictory observations have been obtained from children born in the vicinity of nuclear power plants [14][15][16] .…”

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confidence: 99%

Inheritance of paternal DNA damage by histone-mediated repair restriction

Wang

Meyer

Schumacher

2022

Nature

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How paternal exposure to ionizing radiation affects genetic inheritance and disease risk in the offspring has been a long-standing question in radiation biology. In humans, nearly 80% of transmitted mutations arise in the paternal germline1, but the transgenerational effects of ionizing radiation exposure has remained controversial and the mechanisms are unknown. Here we show that in sex-separated Caenorhabditis elegans strains, paternal, but not maternal, exposure to ionizing radiation leads to transgenerational embryonic lethality. The offspring of irradiated males displayed various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement and aneuploidy. Paternal DNA double strand breaks were repaired by maternally provided error-prone polymerase theta-mediated end joining. Mechanistically, we show that depletion of an orthologue of human histone H1.0, HIS-24, or the heterochromatin protein HPL-1, could significantly reverse the transgenerational embryonic lethality. Removal of HIS-24 or HPL-1 reduced histone 3 lysine 9 dimethylation and enabled error-free homologous recombination repair in the germline of the F1 generation from ionizing radiation-treated P0 males, consequently improving the viability of the F2 generation. This work establishes the mechanistic underpinnings of the heritable consequences of paternal radiation exposure on the health of offspring, which may lead to congenital disorders and cancer in humans.

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Muller and mutations: mouse study of George Snell (a postdoc of Muller) fails to confirm Muller’s fruit fly findings, and Muller fails to cite Snell’s findings

Calabrese,

Selby

2024

Arch Toxicol

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Mutation induction in the mouse and human germline

Cited by 6 publications

References 77 publications

Characteristics of induced mutations in offspring derived from irradiated mouse spermatogonia and mature oocytes

Characteristics of induced mutations in offspring derived from irradiated mouse spermatogonia and mature oocytes

Inheritance of paternal DNA damage by histone-mediated repair restriction

Muller and mutations: mouse study of George Snell (a postdoc of Muller) fails to confirm Muller’s fruit fly findings, and Muller fails to cite Snell’s findings

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