Genetic and Developmental Implications for Trace Metal metabolism from Mutant and Inbred Strains of Animals
Owen M. Rennert, Wai-Yee Chan in Metabolism of Trace Metals in Man, 2017
It is unlikely that any such degree of redundancy would occur or, if it did, would give rise to a viable genotype for the whole organism. Nevertheless, gene duplication is the presumed phylogenetic basis for acquisition of gene redundancy, as is commonly understood for the myoglobin and hemoglobin genes; numerous other redundant structural genes, as well as the two MT genes, may have originated also by gene duplication. Although much is known about MT, the genetic map location of the MT structural genes is still unknown. This may be due principally to the fact that there are no known or easily identifiable isothionein differences within MT-1 or MT-2; the determination of linkage maps requires such identifiable differences and the observance of recombinations with other known chromosomal markers.
DNA-Binding Proteins and DNA-Synthesizing Enzymes in Eukaryotes
Lubomir S. Hnilica in Chromosomal Nonhistone Proteins, 2018
Mammalian cells contain at least three distinct DNA polymerases, i.e., DNA polymerases α, β, and γ Experimental evidence suggests that DNA polymerase α is responsible for DNA replication and DNA polymerase β seems to be involved in DNA repair. DNA polymerase γ is required in mitochondrial DNA replication. However, the role of nuclear DNA polymerase γ is still unknown. The infidelity of DNA polymerase α in DNA synthesis was demonstrated in malignant cells and cells induced by carcinogens. Chromosome duplication is discontinuous in nature. DNA ligases join the intermediate fragments to high molecular DNA. DNA-binding proteins unwind DNA helix, while others bind to the single-stranded DNA and even stimulate homologous DNA polymerase activities.
Neuromuscular disorders
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
Molecular studies show considerable heterogeneity, so predictive or prenatal DNA testing in CMT2 is feasible at present only in those families where a specific defect has been identified. Testing of large gene panels, which will often include the genes responsible for atypical types of SMA, can be helpful in reaching the diagnosis when CMT is not caused by the gene duplication of CMT1A, and especially in CMT type 2.
In vitro genotoxic and cytotoxic effects of some paraben esters on human peripheral lymphocytes
Published in Drug and Chemical Toxicology, 2019
Devrim Güzel Bayülken, Berrin Ayaz Tüylü
The number of CAs were also increased after the treatment of cells with paraben esters at 24 and 48 h, except after butyl paraben and isopropyl paraben treatment for 48 h when compared with the solvent control. PBs induced five types of chromosomal aberration, indicating their clastogenic effects. These were chromatid breaks, chromosome breaks, sister-chromatid union, dicentric chromosomes and ring chromosomes. In this study, chromatid and chromosome breaks have been observed as the most common aberrations. This may result from breaking the phosphodiester backbone of DNA (Rencüzoğulları 2004). Occurrence of CAs, especially breaks, may indicate that possible effects of chemicals after chromosome duplication at the G2 phase of the cell cycle. An increased number of CAs in peripheral blood lymphocytes of healthy individuals represent a marker of susceptibility to cancer (Boffetta et al. 2007). In a study, the propyl paraben and butyl paraben increased the CAs and SCEs in CHO-K1 cells. Also, these chemicals caused DNA migration in the comet assay (Tayama et al.2008). The results of CBMN assay corroborate the CA assay, because micronuclei provide an indirect measurement of the induction of structural CA’s.
Cytogenetic effects of antidiabetic drug metformin
Published in Drug and Chemical Toxicology, 2022
Deniz Yuzbasioglu, Jalank H. Mahmoud, Sevcan Mamur, Fatma Unal
To the best of our knowledge, there have been limited and conflicting studies on the genotoxicity of MET in human lymphocytes. However, the cytotoxic and genotoxic effects of MET and its combinations with other antidiabetic drugs on different cells were previously reported. The results of the present study showed that MET significantly increased the frequency of CAs and CAs/cell in all the concentrations at long-term (48 h) treatment (except 12.5 µg/mL) compared to the negative control in human lymphocytes. However, it did not affect the frequency of CAs at 24 h treatment. MET commonly induced chromatid and chromosome breaks. These aberrations indicated that the chemical may act possibly after the chromosome duplication at the G2 phase of the cell cycle (Biswas et al.2004, Norppa et al.2006, Ginzkey et al.2014). MET also significantly increased the frequency of SCEs/cell at both treatment periods (except 12.5 µg/mL at 24 h) versus the negative control in this study. However, Sant’Anna et al. (2013) demonstrated that MET (12.5, 25, and 50 µM) did not show any significant increase in the frequency of CAs in human lymphocytes. Similarly, in another study, MET (114.4 and 572 µg/ml) did not affect the frequency of CAs in Chinese hamster ovary cells (Amador et al.2012). These discrepancies between results may be generated from the differences in the cell types and concentrations used in these studies.
Corpus Callosum Abnormalities and Short Femurs in Beckwith–Wiedemann Syndrome: A Report of Two Fetal Cases
Published in Fetal and Pediatric Pathology, 2018
Aurélie Beaufrère, Maryse Bonnière, Julia Tantau, Philippe Roth, Elodie Schaerer, Fréderic Brioude, Irène Netchine, Bettina Bessières, Antoinette Gelot, Michel Vekemans, Ferechté Razavi, Delphine Heron, Tania Attié-Bitach
Beckwith–Wiedemann syndrome (BWS) (OMIM #130650) is the most common overgrowth syndrome [1–3]. Molecular heterogeneity is observed in BWS with several genetic and/or epigenetic alterations in imprinted growth regulatory genes at 11p15.5 [1–5]. Approximately 85% of reported BWS cases are sporadic, while the remaining 15% are familial [5]. Clinical features are highly variable, including neonatal macrosomia, post-natal overgrowth, abdominal wall defects (omphalocele, umbilical hernia, diastasis recti), macroglossia, organomegaly, nephro-ureteral malformations, ear anomalies, capillary malformations (hemangioma and nevus flammeus), hypoglycemia, and predisposition to develop embryonic tumors in infancy [1,3,6]. Placenta anomalies are also observed [7,8]. Possible patterns include autosomal dominant inheritance with variable expressivity, contiguous gene duplication at 11p15, and genomic imprinting resulting from a defective or absent copy of the maternally derived gene. Specific phenotype–epigenotype correlations have been reported and recurrence risk estimation is guided by the molecular etiology [5]. Brains malformations were occasionally reported, mainly posterior fossa abnormalities [9–14].
Related Knowledge Centers
- DNA
- DNA Repair
- DNA Replication
- Molecular Evolution
- Retrotransposon
- Slipped Strand Mispairing
- Gene
- Ectopic Recombination
- Aneuploidy
- Polyploidy