Chromothripsis—Explosion in Genetic Science

Shorokhova, Mariia; Nikolsky, Nikolay; Гринчук, Т. М.

doi:10.3390/cells10051102

Cited by 15 publications

(19 citation statements)

References 93 publications

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“…Such a configuration is reminiscent of an aberrant Ds element studied McClintock that generated localized mutagenic events. These break‐induced outcomes were similar to those produced by the process of chromothripsis, [ 49,50 ] a mutagenic phenomenon that scrambles of the gene order of chromosomes and amplifies certain sequences in cancer cells, contributing further to tumorigenesis. Despite these imperfect DNA repair outcomes, ERACRs can efficiently delete and replace a gene‐drive in population cages, particularly when given an added fitness advantage.…”

Section: Gene‐drives Allelic‐drives and Drive Neutralizing Elementsmentioning

confidence: 83%

Active genetics comes alive

Bier

2022

BioEssays

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Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based "active genetic" elements developed in 2015 bypassed the fundamental rules of traditional genetics. Inherited in a super-Mendelian fashion, such selfish genetic entities offered a variety of potential applications including: gene-drives to disseminate gene cassettes carrying desired traits throughout insect populations to control disease vectors or pest species, allelic drives biasing inheritance of preferred allelic variants, neutralizing genetic elements to delete and replace or to halt the spread of gene-drives, splitdrives with the core constituent Cas9 endonuclease and guide RNA (gRNA) components inserted at separate genomic locations to accelerate assembly of complex arrays of genetic traits or to gain genetic entry into novel organisms (vertebrates, plants, bacteria), and interhomolog based copying systems in somatic cells to develop tools for treating inherited or infectious diseases. Here, we summarize the substantial advances that have been made on all of these fronts and look forward to the next phase of this rapidly expanding and impactful field.

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Section: Gene‐drives Allelic‐drives and Drive Neutralizing Elementsmentioning

confidence: 83%

Active genetics comes alive

Bier

2022

BioEssays

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“…Initially, the scientific literature has been suggesting exogenous factors that were supposed to severely impact the double-stranded DNA structure [ 15 , 16 ]. This arising theory has been undermined due to the fact that exogenous stress factors do not impact the genome selectively when chromothripsis may be restricted to certain arms of chromosomes, although it never applies to the entire genome [ 17 ]. Back in 2011, Tubio and Estwill suggested several explanations for the chromothripsis onset.…”

Section: Chromothripsis (Cth)mentioning

confidence: 99%

“…A breakage of the envelope’s continuity leads to the disruption in its preserved microenvironment, leading to the exposure of its content to the external components of the cytoplasm. This causes DNA shattering, followed by its random reincorporation in the main nucleus [ 2 , 17 , 22 ].…”

Section: Chromothripsis (Cth)mentioning

confidence: 99%

“…This method makes it possible to identify both numerical and structural alterations in the genome. However, NGS has its limitations, namely, the method cannot identify copy-neutral options and breakpoints for structural alterations [ 17 , 67 ]. The RNA-Seq approach enables the detection and characterisation of a fusion or chimeric transcript associated to a complex genome rearrangement [ 67 ].…”

Section: Diagnostics Of Chromothripsismentioning

confidence: 99%

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Insight into the Molecular Basis Underlying Chromothripsis

Ostapińska

Styka

Lejman

2022

IJMS

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Chromoanagenesis constitutes a group of events that arise from single cellular events during early development. This particular class of complex rearrangements is a newfound occurrence that may lead to chaotic and complex genomic realignments. By that, chromoanagenesis is thought to be a crucial factor regarding macroevolution of the genome, and consequently is affecting the karyotype revolution together with genomic plasticity. One of chromoanagenesis-type of events is chromothripsis. It is characterised by the breakage of the chromosomal structure and its reassembling in random order and orientation which results in the establishment of derivative forms of chromosomes. Molecular mechanisms that underlie this phenomenon are mostly related to chromosomal sequestration throughout the micronuclei formation process. Chromothripsis is linked both to congenital and cancer diseases, moreover, it might be detected in subjects characterised by a normal phenotype. Chromothripsis, as well as the other chromoanagenetic variations, may be confined to one or more chromosomes, which makes up a non-uniform variety of karyotypes among chromothriptic patients. The detection of chromothripsis is enabled via tools like microarray-based comparative genomic hybridisation, next generation sequencing or authorial protocols aimed for the recognition of structural variations.

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“…Telomere lengthening mechanisms include telomerase enzymatic activity [ 13 ] and the recombination-based alternative lengthening of telomeres (ALT) [ 14 , 15 , 16 ]. In the absence of telomere-lengthening mechanisms, a cell that has undergone a certain number of replication rounds or adverse exposures enters senescence frequently accompanying by chromosomal instability and chromothripsis [ 17 , 18 ] and, eventually, apoptosis. Therefore, adequate telomere length regulation is the sine qua non of a cell’s normal functioning.…”

Section: Introductionmentioning

confidence: 99%

Telomere Length in Chromosomally Normal and Abnormal Miscarriages and Ongoing Pregnancies and Its Association with 5-hydroxymethylcytosine Patterns

Krapivin

Tikhonov

Efimova

et al. 2021

IJMS

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The present study investigates telomere length (TL) in dividing chorionic cytotrophoblast cells from karyotypically normal and abnormal first trimester miscarriages and ongoing pregnancies. Using Q-FISH, we measured relative TLs in the metaphase chromosomes of 61 chorionic villous samples. Relative TLs did not differ between karyotypically normal samples from miscarriages and those from ongoing pregnancies (p = 0.3739). However, among the karyotypically abnormal samples, relative TLs were significantly higher in ongoing pregnancies than in miscarriages (p < 0.0001). Relative TLs were also significantly higher in chorion samples from karyotypically abnormal ongoing pregnancies than in those from karyotypically normal ones (p = 0.0018) in contrast to miscarriages, where relative TL values were higher in the karyotypically normal samples (p = 0.002). In the karyotypically abnormal chorionic cytotrophoblast, the TL variance was significantly lower than in any other group (p < 0.05). Assessed by TL ratios between sister chromatids, interchromatid TL asymmetry demonstrated similar patterns across all of the chorion samples (p = 0.22) but significantly exceeded that in PHA-stimulated lymphocytes (p < 0.0001, p = 0.0003). The longer telomere was predominantly present in the hydroxymethylated sister chromatid in chromosomes featuring hemihydroxymethylation (containing 5-hydroxymethylcytosine in only one sister chromatid)—a typical sign of chorionic cytotrophoblast cells. Our results suggest that the phenomena of interchromatid TL asymmetry and its association to 5hmC patterns in chorionic cytotrophoblast, which are potentially linked to telomere lengthening through recombination, are inherent to the development programme. The TL differences in chorionic cytotrophoblast that are associated with karyotype and embryo viability seem to be determined by heredity rather than telomere elongation mechanisms. The inheritance of long telomeres by a karyotypically abnormal embryo promotes his development, whereas TL in karyotypically normal first-trimester embryos does not seem to have a considerable impact on developmental capacity.

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Chromothripsis—Explosion in Genetic Science

Cited by 15 publications

References 93 publications

Active genetics comes alive

Active genetics comes alive

Insight into the Molecular Basis Underlying Chromothripsis

Telomere Length in Chromosomally Normal and Abnormal Miscarriages and Ongoing Pregnancies and Its Association with 5-hydroxymethylcytosine Patterns

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