Mechanisms of change in gene copy number

By P. Hastings, J. Lupski, S. Rosenberg, G. Ira. Nature reviews genetics, 2009

1,298 citations recorded by the source corpus.

Deletions and duplications of chromosomal segments (copy number variants, CNVs) are a major source of variation between individual humans and are an underlying factor in human evolution and in many diseases, including mental illness, developmental disorders and cancer. CNVs form at a faster rate than other types of mutation, and seem to do so by similar mechanisms in bacteria, yeast and humans. Here we review current models of the mechanisms that cause copy number variation. Non-homologous end-joining mechanisms are well known, but recent models focus on perturbation of DNA replication and replication of non-contiguous DNA segments. For example, cellular stress might induce repair of broken replication forks to switch from high-fidelity homologous recombination to non-homologous repair, thus promoting copy number change.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7acbf8dd6d2e4f0efbb5b5fcfe32a95804b4b4ab

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Citations in the corpus

Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations (2012, positive): “NHEJ-mediated repair of shattered DNA fragments appears more likely to be involved in this context, as it is difficult to reconcile the model of MMBIR with the massive rearrangements (including complex double-minute chromosomes) we detected in association with chromothripsis.”
Playing the end game: DNA double-strand break repair pathway choice. (2012, background): “Inaccurate template selection at direct repeats, such as the rDNA, can drive copy number changes (Hastings et al., 2009).”
COMPLEX LANDSCAPES OF SOMATIC REARRANGEMENT IN HUMAN BREAST CANCER GENOMES (2009, positive): “These differences are unlikely to be due to chance (p 0.001) and suggest that there are at least two classes of NHEJ repair which are operative to different extents in different breast cancers 21 .”
Long-read human genome sequencing and its applications (2020, neutral): “Ironically, these regions also experience some of the highest mutation rates, both in the germline and in the soma 3,12 14 .”
Cancer Evolution: Mathematical Models and Computational Inference (2014, background): “By the nature of the DNA replication process all genomic rearrangement events have a specific start and end, duplicating or deleting all bases between those two loci (Hastings et al. 2009).”
Genome evolution in fungal plant pathogens: looking beyond the two-speed genome model (2020, neutral): “However, this observation is inconsistent with data from pathogen genomes where heterochromatic regions are often unstable or enriched in copy number variations (Hastings et al. , 2009; M € oller et al. , 2019; Plissonneau et al. , 2018; Schotanus et al. , 2015; Seidl et al. , 2016).”
DNA breaks and chromosome pulverization from errors in mitosis (2012, background): “; and (2) aberrant DNA replication resulting in fork stalling and template switching or microhomology-mediated break-induced replicatio”