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Preimplantation Genetic Testing for Aneuploidies: Where We Are and Where We're Going
Published in Darren K. Griffin, Gary L. Harton, Preimplantation Genetic Testing, 2020
Andrea Victor, Cagri Ogur, Alan Thornhill, Darren K. Griffin
Mosaicism was first documented in human embryos with FISH [3,4,52,114]. Since then, a number of different mitotic error mechanisms have been proposed to explain mosaicism: mitotic nondisjunction, anaphase lagging, formation of multinuclei and/or micronuclei, centriole/centrosome dysregulation, and endoreplication [102,115–117]. Mitotic nondisjunction means that sister chromatids of a chromosome are not correctly separated during cell division, resulting in one trisomic and one monosomic daughter cell. Anaphase lagging is an event leading to monosomy in one of the daughter cells at mitosis, because a chromatid does not become incorporated into the nucleus. In mosaic embryos, there is a documented increased incidence of monosomies compared to trisomies, suggesting that anaphase lagging might be the principal mechanism creating mosaicism [12,118,119]. Micronuclei, or small nucleus-like structures, are thought to arise when chromosomal material forms its own nuclear membrane. Since proper kinetochores are absent, the chromosomal content of micronuclei are unable to undergo regulated mitosis, likely resulting in mosaicism in daughter cells [116,120]. Finally, endoreplication without subsequent division could hypothetically result in mosaicism but has not been documented for individual chromosomes, but rather for entire chromosomal complements [115].
Bloom Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
SCE is a process employed by sexually reproducing organisms to promote genetic diversity in offspring and maintain genome stability at the same time. During meiosis that generates haploid gametes from a diploid progenitor, one round of DNA replication (which segregates homologous chromosomes inherited from different parents) is followed by two successive nuclear divisions (the second of which separates sister chromatids). Triggered by self-inflicted DNA DSB, recombination takes place between homologous chromosomes, and two sister chromatids rejoin with one another and exchange regions of the parental strands in the duplicated chromosomes. Alterations in the BLM protein hinder its ability to unwind DNA for subsequent DNA replication and repair, leading to an increased frequency of SCE (Figure 64.1) [16].
Genetics
Published in Rachel U Sidwell, Mike A Thomson, Concise Paediatrics, 2020
Rachel U Sidwell, Mike A Thomson
NB: After the S phase of the cell cycle, the DNA has already replicated, so the cell contains two identical copies of each of the 46 chromosomes. The identical copies are joined together at a centromere and are called sister chromatids, making up one chromosome. Because the chromosomes are studied in metaphase of mitosis when they are most condensed, we actually always Look at DNA that has replicated, the sister chromatids joined together and appearing as 46 separate chromosome bodies.
Targeting the DNA damage response in pediatric malignancies
Published in Expert Review of Anticancer Therapy, 2022
Jenna M Gedminas, Theodore W Laetsch
Double stranded DNA breaks can be repaired using nonhomologous end joining repair (NHEJ) or homologous recombination (HR). The repair mechanism used is based on the stability of the end of the DNA breaks [11]. NHEJ directly ligates broken DNA without the need for a homologous template [12]. Because it does not rely on a template, it is able to repair double stranded breaks in any phase of the cell cycle, however, it is also more prone to error than homologous recombination. Homologous recombination is responsible for the reactivation of stalled replication forks and repair of double stranded DNA breaks and inter-strand crosslinks [13]. The repair process occurs in three steps. The broken end of the chromosome if first paired with the homologous region on the sister chromatid. That strand is then invaded to form a Holliday junction, or DNA crossover, which generates a DNA duplex from the two different chromatids [14]. The Holliday junction is then translocated along the DNA and eventually cleaved by endonucleases to again form separate DNA molecules [14]. These two processes are activated by several kinase pathways, ataxia telangiectasia mutated (ATM), ataxia telangiectasia related (ATR), and DNA-PK, which when mutated, result in defective double-strand break repair [15].
Evaluation of genotoxicity induced by herbicide pendimethalin in fresh water fish Clarias batrachus (linn.) and possible role of oxidative stress in induced DNA damage
Published in Drug and Chemical Toxicology, 2022
Priyanka Gupta, Sushant Kumar Verma
The ability of all chemicals including xenobiotics to impair the genetic information contained within the cell is called genotoxicity which can be evaluated through different biomarkers like evaluation of structural modifications in chromosomes, sister chromatid exchanges, micronucleus frequency, DNA adducts and breaks (Bombail et al.2001). Structural and numerical modifications in chromosomes result from abnormalities in DNA duplication during the ‘S’ phase. Many toxicants that cause chromosomal aberration were also found to induce sister chromatid exchanges. Among these biomarkers comet assay and micronucleus assay are simple, reliable and less time consuming. Comet assay is independent of chromosome number and do not require pretreatment with chemicals like mitotic inhibitors. Therefore it is most frequent and recommended method to detect DNA damage in organisms including fishes (Martins and Costa 2017). Previously it has been reported that herbicides and their commercial formulations induce genotoxicity in fishes (Moreno et al. 2014, Guilherme et al. 2015, Piancini et al. 2015, Ruiz et al.2016, López González et al. 2017).
Genotoxic and mutagenic studies of teratogens in developing rat and mouse
Published in Drug and Chemical Toxicology, 2019
Eyyüp Rencüzoğulları, Muhsin Aydın
Many articles have been published that show in vitro or in vivo tests give extremely reliable results when performed in accordance with international guidelines. Sister chromatid exchange is the exchange of DNA replication products between the homologous loci of sister chromatids that repair DNA double chain breaks by homologous recombination (Sonoda et al. 1999, Helleday 2003). In humans and animals that are exposed to substances known to be mutagenic and carcinogenic, the frequency of SCE is increased and a linear relationship was found between the increase in single-gene mutations and the frequency of SCE (Perry and Evans 1975, Carrano et al. 1978, Albertini et al. 2000). Cheng et al. (1981) reported a similar relationship between the increase of SCE and the formation of in vivo tumors. Unlike CA, SCE is insufficient to determine genotoxic risk alone. However, in experimental studies, SCE is still used as an indicator test that is a suitable method for demonstrating genotoxic effects in humans (Norppa et al. 2006).