Mechanisms of structural chromosomal rearrangement formation

Burssed, Bruna; Zamariolli, Malú; Bellucco, Fernanda Teixeira da Silva; Melaragno, Maria Isabel

doi:10.1186/s13039-022-00600-6

Cited by 48 publications

(35 citation statements)

References 90 publications

(222 reference statements)

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“…On the other hand, FoSTeS/MMBIR usually associated with complex rearrangements including deletions, duplications, and triplications. Those are characteristics of chromoanasynthesis (Burssed et al, 2022; Zepeda‐Mendoza & Morton, 2019).…”

Section: Discussionmentioning

confidence: 99%

Long‐read sequence analysis for clustered genomic copy number aberrations revealed architectures of intricately intertwined rearrangements

Tamura

Shimojima

Okamoto

et al. 2022

American J of Med Genetics Pt A

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Most chromosomal aberrations revealed by chromosomal microarray testing (CMA) are simple; however, very complex chromosomal structural rearrangements can also be found. Although the mechanism of structural rearrangements has been gradually revealed, not all mechanisms have been elucidated. We analyzed the breakpoint‐junctions (BJs) of two or more clustered copy number variations (CNVs) in the same chromosome arms to understand their conformation and the mechanism of complex structural rearrangements. Combining CMA with long‐read whole‐genome sequencing (WGS) analysis, we successfully determined all BJs for the clustered CNVs identified in four patients. Multiple CNVs were intricately intertwined with each other, and clustered CNVs in four patients were involved in global complex chromosomal rearrangements. The BJs of two clustered deletions identified in two patients showed microhomologies, and their characteristics were explained by chromothripsis. In contrast, the BJs in the other two patients, who showed clustered deletions and duplications, consisted of blunt‐end and nontemplated insertions. These findings could be explained only by alternative nonhomologous end‐joining, a mechanism related to polymerase theta. All the patients had at least one inverted segment. Three patients showed cryptic aberrations involving a disruption and a deletion/duplication, which were not detected by CMA but were first identified by WGS. This result suggested that complex rearrangements should be considered if clustered CNVs are observed in the same chromosome arms. Because CMA has potential limitations in genotype–phenotype correlation analysis, a more detailed analysis by whole genome examination is recommended in cases of suspected complex structural aberrations.

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Section: Discussionmentioning

confidence: 99%

Long‐read sequence analysis for clustered genomic copy number aberrations revealed architectures of intricately intertwined rearrangements

Tamura

Shimojima

Okamoto

et al. 2022

American J of Med Genetics Pt A

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“…Fission will disrupt synteny, although very rare [61], and fusion is the major inter-chromosome rearrangement type that also exists at a low frequency. Types of fusion include reciprocally translocated chromosome arms (RTA), end-end joining (EEJ), and nested chromosome fusion (NCF) [62][63][64][65]. Under such conditions, the ancestral chromosomes may be retained as independent chromosomes or entirely nested within the fused chromosomes among extant genomes.…”

Section: Ancestral Eudicot Karyotype Reconstruction and Karyotype Evo...mentioning

confidence: 99%

A high-quality Buxus austro-yunnanensis (Buxales) genome provides new insights into karyotype evolution in early eudicots

et al. 2022

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Background Eudicots are the most diverse group of flowering plants that compromise five well-defined lineages: core eudicots, Ranunculales, Proteales, Trochodendrales, and Buxales. However, the phylogenetic relationships between these five lineages and their chromosomal evolutions remain unclear, and a lack of high-quality genome analyses for Buxales has hindered many efforts to address this knowledge gap. Results Here, we present a high-quality chromosome-level genome of Buxus austro-yunnanensis (Buxales). Our phylogenomic analyses revealed that Buxales and Trochodendrales are genetically similar and classified as sisters. Additionally, both are sisters to the core eudicots, while Ranunculales was found to be the first lineage to diverge from these groups. Incomplete lineage sorting and hybridization were identified as the main contributors to phylogenetic discordance (34.33%) between the lineages. In fact, B. austro-yunnanensis underwent only one whole-genome duplication event, and collinear gene phylogeny analyses suggested that separate independent polyploidizations occurred in the five eudicot lineages. Using representative genomes from these five lineages, we reconstructed the ancestral eudicot karyotype (AEK) and generated a nearly gapless karyotype projection for each eudicot species. Within core eudicots, we recovered one common chromosome fusion event in asterids and malvids, respectively. Further, we also found that the previously reported fused AEKs in Aquilegia (Ranunculales) and Vitis (core eudicots) have different fusion positions, which indicates that these two species have different karyotype evolution histories. Conclusions Based on our phylogenomic and karyotype evolution analyses, we revealed the likely relationships and evolutionary histories of early eudicots. Ultimately, our study expands genomic resources for early-diverging eudicots.

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“…Recent advances in bioinformatics technologies have led to the detection of complex chromosome rearrangements (CCRs) consisting of ≥3 chromosomal breaks in patients with cancer and congenital diseases 1 . These rearrangements caused by catastrophic cellular events can affect phenotype, thereby inducing a disease-promoting environment 2 . In particular, chromoanasynthesis, a recently discovered form of CCRs, is caused by erroneous DNA replication of a single chromosome through fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR), which generates regions of complex rearrangements 3 .…”

Section: Introductionmentioning

confidence: 99%

ARecql5mutant enables complex chromosomal engineering of mouse zygotes

Iwata

Nagahara

Iwamoto

2023

Preprint

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Complex chromosomal rearrangements (CCRs) are often observed in clinical samples from patients with cancer and congenital diseases but are difficult to induce experimentally. For generating animal models, these CCRs must be induced as desired, because they can generate profound genome instability and/or result in cell death. This is the first study to present the establishment of an animal model for CCRs. The disruption ofRecql5, which degrades RAD51 during DNA repair, successfully induces CRISPR/Cas9-mediated CCRs, establishing a mouse model containing triple fusion genes and megabase-sized inversions. Notably, some of these structural features of individual chromosome rearrangements use template switching and microhomology-mediated break-induced replication mechanisms and are reminiscent of the newly described phenomenon chromoanasynthesis. Whole-genome sequencing (WGS) analysis revealed that the structural variants in these mice caused only target-specific rearrangements but not target-independent complex ones. Thus, these data demonstrate that CCRs can be efficiently induced by manipulating DNA repair pathways.

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Mechanisms of structural chromosomal rearrangement formation

Cited by 48 publications

References 90 publications

Long‐read sequence analysis for clustered genomic copy number aberrations revealed architectures of intricately intertwined rearrangements

Long‐read sequence analysis for clustered genomic copy number aberrations revealed architectures of intricately intertwined rearrangements

A high-quality Buxus austro-yunnanensis (Buxales) genome provides new insights into karyotype evolution in early eudicots

ARecql5mutant enables complex chromosomal engineering of mouse zygotes

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