Preimplantation Genetic Testing for Structural Rearrangements
Carlos Simón, Carmen Rubio in Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Translocations are interchromosomal rearrangements that involve two different chromosomes, and may occur between non-homologous chromosomes; these are the most common type of chromosome rearrangement. Translocations occur after a break in two or more chromosomes and interchange of chromosomal fragments between two or more chromosomes. Inherited translocations are commonly innocuous for the carrier, although the carrier usually has high rates of unbalanced gametes following meiotic segregation and unbalanced embryos [18,19]. The risk of unbalanced gametes depends on the chromosome involved, size of the region involved, position of the breakpoints, and the maternal or paternal origin. Consequently, translocation carriers have a greater chance of being infertile and/or having chromosomally abnormal pregnancies that lead to recurrent spontaneous abortions or children with congenital anomalies and mental retardation [16]. The risk of having abnormal offspring is specific for each translocation event.
Oncogenes and Cancer
Pimentel Enrique in Oncogenes, 2020
Amplification of DNA sequences, including proto-oncogene sequences, can occur in eukaryotic cells under certain physiological conditions.106 Oncogene amplification has been suggested as a model for the general process of carcinogenesis.107 This phenomenon could occur through a series of unequal sister chromatid exchanges in different cell cycles. Moreover, chromosome rearrangement may be an essential and intimate step in the amplification process.108 Another possible mechanism for generation of amplified genomic sequences is disproportionate replication, which means that there can occur more than a single initiation of replication in a portion of a chromosome within a single S phase of the cell cycle.109,110 Several experimental results support the latter model of gene amplification.
Preimplantation Genetic Testing and Reproductive Genetics from a Physician's Perspective
Darren K. Griffin, Gary L. Harton in Preimplantation Genetic Testing, 2020
The genetic status of the embryo is one of the essential properties that affects its implantation, the successful course of pregnancy, and the probability of giving birth to a healthy child. Most aneuploid embryos are lost in the preimplantation period or in the first trimester of pregnancy; alternatively, in the event of so-called birthable defects they may result in the birth of a defective child. Structural chromosomal defects lead to reduced fertility and entail the risk of giving birth to a child with a congenital defect as a result of unbalanced chromosomal rearrangement. Gene mutations may lead to a child with so-called monogenic disease. The entirety of these problems is managed through PGT.
Study of mutation from DNA to biological evolution
Published in International Journal of Radiation Biology, 2019
Masako Bando, Tetsuhiro Kinugawa, Yuichiro Manabe, Miwako Masugi, Hiroo Nakajima, Kazuyo Suzuki, Yuichi Tsunoyama, Takahiro Wada, Hiroshi Toki
Here, we demonstrate another sketch of the whole picture of the pathway in Figure 9, which we made based on the detailed explanation made by Maki together with the references of his review paper (Maki and Amu 2002). From this figure, we notice that there are mainly two endpoints, the one is the point mutation and the other is the chromosome rearrangement. As for the point mutation, the main route corresponds to the path 2, indicated in Figure 9, and the damage produced is about 10−9–10−10/base/cycle and most of them can be regarded as the oxidized DNA damage (‘8-oxoG’ is induced by ROS). On the other hand, the DNA damage induced by the replication error is almost completely repaired (corresponding to the path 1 in Figure 9, 10−6–10−11/base/cycle or less) by the proofreading. It must be noted, however, there exists the route 3, whose endpoint is the chromosome rearrangement. This kind of mutation probably leads to severe injuries, yielding the development of cancer (Maki and Amu 2002). From this point of view, we should remind the readers to note the paper on the retrospective analysis of the old data done by mega-mouse project, which is seen in the paper written by Russell and Hunsicker (2012), who reanalyzed the old data obtained from the phenotypes associated to specific seven-locus-tests in view of the microscopic level information, including chromosome mutants and classified the past mutation data into large and other lesions. The pathway from the DNA damage to the chromosome rearrangement may be more important. This problem will be left for future study (Maki and Amu 2002).
Prenatal diagnosis of Wolf-Hirschhorn syndrome at the first trimester using chromosomal microarray analysis
Published in Journal of Obstetrics and Gynaecology, 2019
Mei-Fang Lin, Lv-Yin Huang, Yan-Dong Yang, Dong-Zhi Li
The prevalence of WHS in foetuses with an increased NT is unknown. Actually, the authors detected two cases in a total of 800 foetuses with an increased NT using CMA. The chromosomal rearrangement can be only isolated de novo deletion (4p–), which is evidenced by the present two cases or by familial unbalanced translocations involving 4p and other chromosomes. Accordingly, the clinical manifestations in WHS vary greatly in individual patients, depending on the variability in the extent of the 4p deletion and the complexity of the basic genomic defects. The prognosis involving the psychomotor development in WHS patients is utterly unfavourable since the developmental delay/intellectual disability of a variable degree is present in all and seizures occur in 50–100% of the patients (Battaglia et al. 2009). Therefore, an early prenatal diagnosis would be helpful for parents in their decision making.
Self-reported effects of perceived social support on marital quality in balanced translocation patients and their spouses undergoing preimplantation genetic testing in China: actor–partner interdependence model
Published in Journal of Obstetrics and Gynaecology, 2022
Fengyi Mo, Xiaorui Hu, Qing Ma, Li Zhang, Lanfeng Xing
Chromosomal abnormalities, one of the most frequent causes of genetic diseases (Mierla et al. 2015), are defined as a genetic disease caused by abnormalities in the number, morphology or structure of chromosomes, often resulting in miscarriage, congenital mental retardation, mental retardation and multiple malformations (Chen et al. 2020). The most frequent chromosomal abnormalities are balanced chromosomal rearrangement, sex chromosomal mosaicism and inversion. The rate of a chromosomal anomaly in the general population is 0.37–1.86%; however, the rate in patients with a history of adverse pregnancy is 3.95–14.3% (Liu et al. 2013). Chromosomal abnormalities cannot be treated medically since they are irreversible (Chen et al. 2020). Balanced translocation is a situation in which both breakage and reconnection of chromosomes occur at abnormal positions, including both Robertsonian and reciprocal translocations. Approximately, 0.5–5% of couples with reproductive problems carry a balanced translocation (Munné et al. 2000; Findikli et al. 2003). However, at present, the specific mechanisms underlying balanced translocation remain unclear (Chen et al. 2020).
Related Knowledge Centers
- Chromosomal Inversion
- Chromosomal Translocation
- Chromosome Abnormality
- Gene Duplication
- Mutation
- Chromosome
- Genetics
- Deletion
- Nucleic Acid Double Helix
- Gene