Template switching mechanism drives the tandem amplification of chromosome 20q11.21 in human pluripotent stem cells
Jason A Halliwell; Duncan Baker; Kim Judge; Michael A Quail; Karen Oliver; Emma Betteridge; Jason Skelton; Peter W Andrews; Ivana Barbaric
Show abstract
Copy number variants (CNVs) are genomic rearrangements implicated in numerous congenital and acquired diseases, including cancer. In human pluripotent stem cells (PSC), the appearance of culture-acquired CNVs prompted concerns for their use in regenerative medicine applications. A particularly common problem in PSC is the occurrence of CNVs in the q11.21 region of chromosome 20. However, the exact mechanisms of origin of this amplicon remains elusive due to the difficulty in delineating its sequence and breakpoints. Here, we used long-range Nanopore sequencing on two examples of this CNV, present as a duplication in one and a triplication in another line. The CNVs were arranged in a head-to-tail orientation in both lines, with sequences of microhomologies flanking or overlapping both the proximal and distal breakpoints. These breakpoint signatures point to a specific mechanism of template switching in CNV formation, with surrounding Alu sequences likely contributing to the instability of this genomic region.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma 94%
- Genetic Variation as a Long-Distance Modulator of RAD21 Expression in Humans 94%
- A novel RLIM/RNF12 variant disrupts protein stability and function to cause severe Tonne-Kalscheuer syndrome 93%
Similar papers in this journal
- Engineering large chromosomal deletions by CRISPR-Cas9 94%
- Evolutionary hotspots of structural variation drive inter-individual differences in the expression of fusion transcripts in the human brain 94%
- Large-scale expansions and replication stalling of Friedreich's ataxia GAA repeats in an experimental mammalian system 94%
Similar papers in this journal
- Isoform-specific characterization implicates alternative splicing in APOBEC3B as a mechanism restricting APOBEC-mediated mutagenesis 94%
- Single-cell somatic copy number variants in brain using different amplification methods and reference genomes 94%
- Whole genome analysis for 163 guide RNAs in Cas9 edited mice reveals minimal off-target activity 94%
Similar papers in this journal
- Amplification-free long read sequencing reveals unforeseen CRISPR-Cas9 off-target activity 95%
- Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells 94%
- MINTIE: identifying novel structural and splice variants in transcriptomes using RNA-seq data 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.