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• W3094128522 abstract "Abstract Background The accumulation of mtDNA mutations in different tissues from various mouse models has been widely studied especially in the context of mtDNA mutation-driven ageing but has been confounded by the inherent limitations of the most widely used approaches. By implementing a method to sequence mtDNA without PCR amplification prior to library preparation, we map the full unbiased mtDNA mutation spectrum across six distinct brain regions from mice. Results We demonstrate that ageing-induced levels of mtDNA mutations (single nucleotide variants and deletions) reach stable levels at 50 weeks of age but can be further elevated specifically in the cortex, nucleus accumbens (NAc), and paraventricular thalamic nucleus (PVT) by expression of a proof-reading-deficient mitochondrial DNA polymerase, Polg D181A . The increase in single nucleotide variants increases the fraction of shared SNVs as well as their frequency, while characteristics of deletions remain largely unaffected. In addition, Polg D181A also induces an ageing-dependent accumulation of non-coding control-region multimers in NAc and PVT, a feature that appears almost non-existent in wild-type mice. Conclusions Our data provide a novel view of the spatio-temporal accumulation of mtDNA mutations using very limited tissue input. The differential response of brain regions to a state of replication instability provides insight into a possible heterogenic mitochondrial landscape across the brain that may be involved in the ageing phenotype and mitochondria-associated disorders." @default.
• W3094128522 created "2020-10-29" @default.
• W3094128522 creator A5005693637 @default.
• W3094128522 creator A5015711180 @default.
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• W3094128522 creator A5019667159 @default.
• W3094128522 creator A5064271297 @default.
• W3094128522 date "2020-10-23" @default.
• W3094128522 modified "2023-10-16" @default.
• W3094128522 title "Unbiased PCR-free spatio-temporal mapping of the mtDNA mutation spectrum reveals brain region-specific responses to replication instability" @default.
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• W3094128522 doi "https://doi.org/10.1186/s12915-020-00890-5" @default.
• W3094128522 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7585204" @default.
• W3094128522 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33097039" @default.
• W3094128522 hasPublicationYear "2020" @default.
• W3094128522 type Work @default.
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