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De novo deletions and duplications at recombination hotspots in mouse germlines

UID: 10971

Author(s): Lukaszewicz, Agnieszka*, Keeney, Scott, Jasin, Maria* * MSK affiliated

Description
Summary from GEO:

"Numerous DNA double-strand breaks (DSBs) arise during meiosis to initiate homologous recombination. These DSBs are usually repaired faithfully, but here we uncover a new type of mutational event in which deletions form via joining of ends from two closely-spaced DSBs (double cuts) within a single hotspot or at adjacent hotspots on the same or different chromatids. Deletions occur in normal meiosis but are much more frequent when DSB formation is dysregulated in the absence of the ATM kinase. Events between chromosome homologs point to multi-chromatid damage and aborted gap repair. Some deletions contain DNA from other hotspots, indicating that double cutting at distant sites creates substrates for insertional mutagenesis. End joining at double cuts can also yield tandem duplications or extrachromosomal circles. Our findings highlight the importance of DSB regulation and reveal a previously hidden potential for meiotic mutagenesis that is likely to affect human health and genome evolution."

Overall design from GEO:

"Amplicon deep sequencing was applied to detect deletions at a single mouse DSB hotspot on Chr1. Four overlapping amplicons across the hotspot were amplified for each genotype: Atm–/–, Atm+/–, Atm+/+ and Spo11–/–). Sixteen samples in total."
Subject of Study
Subject(s)
Access via GEO


Accession #: GSE182210

Access via BioProject


Accession #: PRJNA755308

Access via SRA


Accession #: SRP332728

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, BioProject, and SRA databases provide open access to these files.
Associated Publications
Equipment Used
Dataset Format(s)
TAR, TXT
Dataset Size
1.4 MB
Data Catalog Record Updated
2023-10-23