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Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring

Understanding the effects of environmental exposures on germline mutation rates has been a decades-long pursuit in genetics. We used next-generation sequencing and comparative genomic hybridization arrays to investigate genome-wide mutations in the offspring of male mice exposed to benzo(a)pyrene (B...

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Autores principales: Beal, Marc A., Meier, Matthew J., Williams, Andrew, Rowan-Carroll, Andrea, Gagné, Rémi, Lindsay, Sarah J., Fitzgerald, Tomas, Hurles, Matthew E., Marchetti, Francesco, Yauk, Carole L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586636/
https://www.ncbi.nlm.nih.gov/pubmed/31240266
http://dx.doi.org/10.1038/s42003-019-0476-5
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author Beal, Marc A.
Meier, Matthew J.
Williams, Andrew
Rowan-Carroll, Andrea
Gagné, Rémi
Lindsay, Sarah J.
Fitzgerald, Tomas
Hurles, Matthew E.
Marchetti, Francesco
Yauk, Carole L.
author_facet Beal, Marc A.
Meier, Matthew J.
Williams, Andrew
Rowan-Carroll, Andrea
Gagné, Rémi
Lindsay, Sarah J.
Fitzgerald, Tomas
Hurles, Matthew E.
Marchetti, Francesco
Yauk, Carole L.
author_sort Beal, Marc A.
collection PubMed
description Understanding the effects of environmental exposures on germline mutation rates has been a decades-long pursuit in genetics. We used next-generation sequencing and comparative genomic hybridization arrays to investigate genome-wide mutations in the offspring of male mice exposed to benzo(a)pyrene (BaP), a common environmental pollutant. We demonstrate that offspring developing from sperm exposed during the mitotic or post-mitotic phases of spermatogenesis have significantly more de novo single nucleotide variants (1.8-fold; P < 0.01) than controls. Both phases of spermatogenesis are susceptible to the induction of heritable mutations, although mutations arising from post-fertilization events are more common after post-mitotic exposure. In addition, the mutation spectra in sperm and offspring of BaP-exposed males are consistent. Finally, we report a significant increase in transmitted copy number duplications (P = 0.001) in BaP-exposed sires. Our study demonstrates that germ cell mutagen exposures induce genome-wide mutations in the offspring that may be associated with adverse health outcomes.
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spelling pubmed-65866362019-06-25 Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring Beal, Marc A. Meier, Matthew J. Williams, Andrew Rowan-Carroll, Andrea Gagné, Rémi Lindsay, Sarah J. Fitzgerald, Tomas Hurles, Matthew E. Marchetti, Francesco Yauk, Carole L. Commun Biol Article Understanding the effects of environmental exposures on germline mutation rates has been a decades-long pursuit in genetics. We used next-generation sequencing and comparative genomic hybridization arrays to investigate genome-wide mutations in the offspring of male mice exposed to benzo(a)pyrene (BaP), a common environmental pollutant. We demonstrate that offspring developing from sperm exposed during the mitotic or post-mitotic phases of spermatogenesis have significantly more de novo single nucleotide variants (1.8-fold; P < 0.01) than controls. Both phases of spermatogenesis are susceptible to the induction of heritable mutations, although mutations arising from post-fertilization events are more common after post-mitotic exposure. In addition, the mutation spectra in sperm and offspring of BaP-exposed males are consistent. Finally, we report a significant increase in transmitted copy number duplications (P = 0.001) in BaP-exposed sires. Our study demonstrates that germ cell mutagen exposures induce genome-wide mutations in the offspring that may be associated with adverse health outcomes. Nature Publishing Group UK 2019-06-20 /pmc/articles/PMC6586636/ /pubmed/31240266 http://dx.doi.org/10.1038/s42003-019-0476-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Beal, Marc A.
Meier, Matthew J.
Williams, Andrew
Rowan-Carroll, Andrea
Gagné, Rémi
Lindsay, Sarah J.
Fitzgerald, Tomas
Hurles, Matthew E.
Marchetti, Francesco
Yauk, Carole L.
Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring
title Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring
title_full Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring
title_fullStr Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring
title_full_unstemmed Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring
title_short Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring
title_sort paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586636/
https://www.ncbi.nlm.nih.gov/pubmed/31240266
http://dx.doi.org/10.1038/s42003-019-0476-5
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