Duplex sequencing identifies genomic features that determine susceptibility to benzo(a)pyrene-induced in vivo mutations

Autor: Danielle P. M. LeBlanc, Matthew Meier, Fang Yin Lo, Elizabeth Schmidt, Charles Valentine, Andrew Williams, Jesse J. Salk, Carole L. Yauk, Francesco Marchetti
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: BMC Genomics, Vol 23, Iss 1, Pp 1-15 (2022)
Druh dokumentu: article
ISSN: 1471-2164
DOI: 10.1186/s12864-022-08752-w
Popis: Abstract Exposure to environmental mutagens increases the risk of cancer and genetic disorders. We used Duplex Sequencing (DS), a high-accuracy error-corrected sequencing technology, to analyze mutation induction across twenty 2.4 kb intergenic and genic targets in the bone marrow of MutaMouse males exposed to benzo(a)pyrene (BaP), a widespread environmental pollutant. DS revealed a linear dose-related induction of mutations across all targets with low intra-group variability. Heterochromatic and intergenic regions exhibited the highest mutation frequencies (MF). C:G > A:T transversions at CCA, CCC and GCC trinucleotides were enriched in BaP-exposed mice consistent with the known etiology of BaP mutagenesis. However, GC-content had no effect on mutation susceptibility. A positive correlation was observed between DS and the “gold-standard” transgenic rodent gene mutation assay. Overall, we demonstrate that DS is a promising approach to study in vivo mutagenesis and yields critical insight into the genomic features governing mutation susceptibility, spectrum, and variability across the genome.
Databáze: Directory of Open Access Journals
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