The Fight Against Cancer
Nathan Keighley in Miraculous Medicines and the Chemistry of Drug Design, 2020
Chromosomes containing mutated genes will become more prevalent if cell division and replication of the defective DNA is allowed to continue unimpeded, when the necessary control mechanisms fail, and this vastly increases the risk of cancer; as defective cells multiply in number, they can grow uncontrollably and defective genes can be inherited in gametes, if damage occurs during meiosis. Humans have 22 pairs of homologous chromosomes (X and Y) and a pair of sex chromosomes; a total of 46 chromosomes, known as the diploid number. The diploid number varies between species, for example dogs have 78. These are always even numbers because half comes from each parent. The chromosomes are dispersed throughout the nucleus and each comprise a single molecule of DNA that is supercoiled, held in place by protein molecules called histones. The chromosomes are only distinctly visible under the microscope during cell division.
Chromosome Pairing and Fertility in Polyploids
Christopher B. Gillies in Fertility and Chromosome Pairing: Recent Studies in Plants and Animals, 2020
Polyploidy can be subdivided into at least two types. In autopolyploids, only one basic genome is present as multiple copies, while in allopolyploids, genomes from two or more species origins are present, presumably following a hybridization event. Since the generation of viable hybrids and allopolyploids requires some phylogenetic relationship between the parental species, it is expected that some homology will exist between chromosomes of the genomes in an allopolyploid. This has resulted in the introduction of the term segmental allopolyploid to describe a polyploid containing partially homologous (homoeologous) genomes.19 The existence of partially homologous chromosomes in allopolyploids allows for variability in pairing behavior so that in such cases pairing may be between identical homologues from one genome type — autosyndesis, or it may be between partially homologous chromosomes from different genomes — allosyndesis.20 While in practice it is often difficult to classify many polyploids as strict autopolyploids or allopolyploids, for convenience I deal separately with issues peculiar to each type.
Molecular Approaches Towards the Isolation of Pediatric Cancer Predisposition Genes
John T. Kemshead in Pediatric Tumors: Immunological and Molecular Markers, 2020
When total genomic DNA is “cut” with a particular enzyme, a heterogeneous population of characteristic restriction fragments is produced. Each fragment has a fixed length, the restriction fragment length (RFL). Agarose gels can be used to separate these fragments according to size. Using standard techniques, developed by Southern5 and Rigby et. al.,6 radioactive DNA probes can be used to hybridize with, i.e., “recognize”, homologous sequences within the heterogenous population. This homology is manifested as a band (or set of bands)on an autoradiograph at one or more specific locations determined by the size of the fragment being recognized (Figure 1). If there is no sequence variation between individuals in the region of the chromosome recognized by the probe, a consistent band pattern is produced at the same position on the gel. However, any variation in DNA sequence that affects a given restriction site, such that an existing one is removed or a new one is created, will generate variations in the band pattern observed. Since the bands produced are polymorphic, the variation is referred to as a restriction fragment length polymorphism (RFLP). This principle is illustrated in Figure 2. If an individual is heterozygous for the polymorphic variants, then both of the individual homologous chromosomes can be identified (see Figure 2). Differences in DNA sequence at the same locus are allelic and the bands produced on the autoradiograph are conveniently referred to as alleles.
Genetic variations as molecular diagnostic factors for idiopathic male infertility: current knowledge and future perspectives
Published in Expert Review of Molecular Diagnostics, 2021
Mohammad Karimian, Leila Parvaresh, Mohaddeseh Behjati
Balanced chromosomal translocations involve the breakage of two chromosomes and abnormal repair of chromosomal fragments resulting in the transfer of genetic material from one chromosome to another without loss of any genetic material. In vast majority of cases, carriers of balanced translocations are phenotypically normal, unless one of the breakpoints at the site of translocation disrupts an important gene. Chromosomal translocation, while phenotypically normal, may experience fertility loss, miscarriage, or birth defects. Normal meiotic segregation of these translocations in gametes can lead to duplication or deletion of chromosomal regions involved in translocation [171]. Like chromosomal translocations, inversions can lead to infertility, miscarriage, and birth defects. During meiosis, chromosomes are forced to form specialized structures, so that homologous chromosomes can be paired. Chromosomal inversions can affect these specialized structures. Research on the production of unbalanced gametes in balanced inversion carriers has been done to a much lesser extent than translocations. However, a handful of studies have reported an unbalanced sperm range of 1–54% [172–174].
Prevalence of SLCO1B1 single nucleotide variations and their association with hypercholesterolaemia in hypercholesterolemic patients in Gauteng, South Africa
Published in Xenobiotica, 2021
Rene de Beer, Kim Outhoff, Alisa Phulukdaree, Prashilla Soma
The rs2306283 variant on the SLCO1B1 gene is also suspected of being associated with decreased activity of the SLCO1B1 transporter, resulting in decreased clearance of statins from the circulation (Lin et al. 2011). However, the different haplotypes, i.e. particular combinations of alleles located on one of two homologous chromosomes at a nearby SNV, (Consortium IH 2003) associated with this SNV have yielded different results (Santos et al. 2012). In the study on the effect of SLCO1B1 rs2306283 *15 on the pharmacokinetic profiles of pravastatin and pitavastatin, a strong association between the altered transport of these statins and the specified haplotype was identified (Deng et al. 2008). However, two separate studies to determine the association of this variant with statin intolerance indicated no significant association between rs2306283 and atorvastatin and rosuvastatin induced myopathy, respectively (Puccetti et al. 2010; Santos et al. 2012). The data on the effect, as well as its combined effect with other statins is still inconclusive and limited (Stewart 2013).
Zoledronic acid induces cytogenetic toxicity in male germline cells of Swiss albino mice
Published in Drug and Chemical Toxicology, 2019
Ramakrishna Dasari, Sunil Misra
Aberrant chromosomal segregation is a consequence of errors in the series of programed and sequential events occurring at prophase-I of meiosis defined by a number of characteristic morphological changes associated with the pairing of homologous chromosomes, synapsis, asynapsis, and recombination (Garcia-Muse and Boulton 2007). For analyzing the cytogenetic toxicity of ZA, three different concentrations (2, 4, and 8 mg/kg b.wt.) were exposed to mice. The group of positive control mice that received CP induced significantly higher percentage of CAs in the spermatogonial cells which are in agreement with the earlier reports (Rathenberg 1975, Choudhury et al. 2002). Further, CP induced a significantly higher percentage of aberrant primary spermatocytes with atypical bivalents at week 4 posttreatment and also significantly higher percentage of abnormal sperms at week 8 posttreatment justifying its clastogenic potential in germline cells.
Related Knowledge Centers
- Centromere
- DNA
- Histone
- Mendelian Inheritance
- Meiosis
- Chromatin
- Chromosome
- Fertilisation
- Gene
- Locus