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Genetic Counseling in Assisted Reproductive Technology
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Although carriers of a balanced chromosomal rearrangement are generally healthy, the rearrangement can cause difficulties conceiving or carrying a child to term. The most common balanced structural rearrangements are translocations, in which segments from two chromosomes dissociate and then rejoin to the reciprocal chromosome, and inversions, where a segment of a single chromosome disassociates but then rejoins in the opposite orientation. Robertsonian translocations are unique types of translocations that involve the acrocentric chromosomes 13, 14, 15, 21, and 22. The chromosomes fuse at the centromere, resulting in a reduction in the total number of chromosomes and the benign loss of the redundant stalks and satellites at the p arm of both chromosomes. A balanced chromosomal rearrangement can lead to difficulty conceiving, spontaneous miscarriage, or the birth of a child with multiple congenital anomalies, depending on the degree of the imbalance. Although balanced in the carrier, structural rearrangements may be unbalanced in the gametes, resulting in developmental abnormalities. In some individuals, the structural rearrangement can impair meiosis and block gametogenesis, especially male spermatogenesis. The disruption of spermatogenesis is variable, even among male relatives carrying the same chromosomal rearrangement. Approximately 1/500 individuals in the general population carry a balanced reciprocal translocation, and approximately 1/1000 individuals carry a balanced Robertsonian translocation. This frequency is likely to be higher in the infertile population.
Genetics of Uterine Leiomyomata
Published in John C. Petrozza, Uterine Fibroids, 2020
C. Scott Gallagher, Cynthia C. Morton
Chromosomal rearrangement is hypothesized to alter gene activity by recombining regions of the genome (Figure 5.1). Breakage and repair may be nonviable in many cases, but, at a low frequency, they can create gene fusions encoding novel chimeric proteins and dysregulate gene expression by introducing foreign regulatory elements or removing native ones. Resolution of chromosomal damage can generate cells with survival or growth advantages and result in benign transformation of a myometrial cell [7,57]. Alternatively, chromosomal instability may mostly be inert, with dysregulated growth resulting from primary mutations elsewhere in the genome [6].
Molecular Approaches Towards the Isolation of Pediatric Cancer Predisposition Genes
Published in John T. Kemshead, Pediatric Tumors: Immunological and Molecular Markers, 2020
Genetic predisposition to Rb can also result from chromosome rearrangements32–34 such as translocations, inversions, and insertions. The chromosome rearrangement is usually carried in a “balanced” form by the parent who is unaffected; inheritance of the unbalanced form confers the predisposition because of a net loss of material from ql4. Figure 8 shows an apparently balanced chromosome translocation from an Rb patient. The ESD levels from red blood cells from this patient were normal suggesting that the breakpoint in this case has occurred within the coding sequence of the Rb gene or its control elements. In two other cases, the translocation has involved the relocation of 13ql4 onto the X chromosome.35,36 The apparent random inactivation of the derivative chromosome responsible for tumor development represents a functional, rather than a physical, deletion of the Rb locus.
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.
Abnormal chromosomes identification using chromosomal microarray
Published in Journal of Obstetrics and Gynaecology, 2022
Yunfang Shi, Xiaozhou Li, Duan Ju, Yan Li, Xiuling Zhang, Ying Zhang
Other implications of this study for clinical practice included correct identification for recurrent risk in future pregnancies and other at-risk relatives. It is important to be alert to the possibility of a chromosome rearrangement in the family with a chromosome anomaly. The detection of the familial chromosomal translocation may direct the investigation of other family members and permit to plan future pregnancies (Gonzalez et al. 2018; Pasińska et al. 2018). In this study, three parents presented chromosomal abnormalities. One (case 3) was previously known, and the other two (case 1 and case 2) were detected after karyotype and CMA analysis. Other cases (cases 4–6) with normal parental karyotypes indicated that they were de novo cases.