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The Genetic Risk of a Couple Aiming to Conceive
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Joe Leigh Simpson, Svetlana Rechitsky, Anver Kuliev
Chromosomal inversions differ mechanistically from translocations but exert similar roles clinically in terms of recurrent miscarriages or abnormal liveborns. Individuals having an inversion are phenotypically normal, but the order of their genes on a specific chromosome is reversed. This arises when a single chromosome undergoes two breaks. In pericentric inversions, one break occurs on the short arm and the other on the long arm. In paracentric inversions, both breaks occur on the same arm (i.e., short or long). In either inversion, DNA repair occurs, but in doing so the delineated chromosomal segment becomes inverted through 180°; thus, the sequence of genes on the chromosome involved is reversed (22). To illustrate, the original gene sequence of ABCDEFGH may become HGFEDCBA. Stephenson and Sierra (16) detected seven inversions among 1893 couples suffering recurrent miscarriages (0.37%), whereas Goddijn (8) detected 9 inversions among 1324 couples (0.68%). Inversions of sufficient length would be expected to be detected by karyotype, based on altered sequences of bands. Importantly, microarray-based comparative genomic hybridization (CGH) or next-generation sequencing (NGS) platforms, based solely on quantity of DNA, cannot identify a balanced inversion because DNA content alone remains unchanged. Analysis based on single nucleotide polymorphisms (karyomapping) can be informative.
Introductory Remarks
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Chromosomal amplification/repetition refers to the presence of extra piece from another chromosome that leads to multiple copies of all chromosomal regions and increases the dosage of the genes located within. Chromosomal deletion refers to loss of large chromosomal regions including certain genes (with interstitial deletion being defined as an intra-chromosomal deletion that removes a segment of DNA from a single chromosome and thus apposes previously distant genes, and loss of heterozygosity being loss of one allele, either by a deletion or a genetic recombination event, in an organism with two different alleles). Chromosomal translocation refers to interchange of genetic parts from nonhomologous chromosomes, and chromosomal inversion refers to reversion of the orientation of a chromosomal segment [6].
Mechanisms of Resistance to Antineoplastic Drugs
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Philip J. Vickers, Alan J. Townsend, Kenneth H. Cowan
Schimke114-116 has proposed that both HSRs and DMs arise by the same events. First, overreplication of DNA occurs by multiple initiations of DNA replication. The initial reduplication of DNA is apparently followed by a step involving DNA recombination. When the recombination event occurs chromosomally, an HSR may develop at the site of the integrated gene. When this event occurs extrachromosomally, a DM is formed. It has been suggested that homologous recombination of the amplified DNA sequences that are transiently formed may result in a number of other cytogenetic aberrations in addition to HSRs and DMs, including sister chromatid exchanges, dicentric chromosomes, and chromosomal inversions.116
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
A 37-year-old primigravida was referred to our centre for cordocentesis due to foetal IUGR and smaller limbs than normal gestational weeks. Her medical history included an abnormal karyotype 46,XX,inv(11)(p15.4q23) and infertility for about 10 years. The pregnancy was achieved via invitro fertilisation. The pregnant woman received routine prenatal care at an outside institution and declined amniocentesis in the second trimester. She chose non-invasive prenatal testing (NIPT), which showed low risk for trisomy 21, 18 and 13. Cordocentesis was carried out at a gestational age of 30 weeks, and foetal karyotype was normal (46,XX). SNP-array result showed a 10.0 Mb deletion in 11q24.2q25 of chromosome 11 containing 41 OMIM genes involved KCNJ1, JAM3 and KIRREL (Figure 3). However, the partial deletion of chromosome 11 was explained by the maternal chromosomal inversion and the couple opted to terminate the pregnancy after genetic counselling.
Ad Astra – telomeres in space!
Published in International Journal of Radiation Biology, 2022
Susan M. Bailey, Jared J. Luxton, Miles J. McKenna, Lynn E. Taylor, Kerry A. George, Sameer G. Jhavar, Gregory P. Swanson
Ionizing radiations are exquisite in their ability to induce DNA damage in the form of prompt DSBs as well, which when mis-repaired can result in a variety of well-described chromosome rearrangements (Cornforth et al. 2021). Utilizing dGH, and for the first time in astronauts, we detected increased frequencies of intra-chromosomal inversions during spaceflight, which persisted after spaceflight, potentially suggestive of stem-cell damage, clonal hematopoiesis, and/or genome instability (Garrett-Bakelman et al. 2019; Luxton et al. 2020; Luxton et al. 2020; Trinchant et al. 2020). Also consistent with exposure to the space radiation environment, strong relationships between post-spaceflight chromosome aberration frequencies, specifically inversions, and lifetime radiation dose estimates were identified (Luxton et al. 2020), providing additional evidence of their persistence after exposure (McKenna et al. 2019), and further support inversions as informative biomarkers of radiation exposure associated with spaceflight (Hada et al. 2007; Ray et al. 2014; Garrett-Bakelman et al. 2019). In the context of fractionated doses and IMRT, frequencies of radiation-induced dicentrics and inversions were similarly associated with dose-dependent decreases in lymphocyte counts following treatment (Luxton et al. 2021).
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].