China
Africa
Explore chapters and articles related to this topic
Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Two additional mechanisms of allelic variation involve expression of VSG genes that are not initially adjacent to promoters. Some of these genes remain unexpressed until a crossover event places one of them in an expression site. As the crossover occurs, the new VSG gene replaces the previously expressed VSG gene, which is then moved away from the promoter site. Finally, many VSG genes are pseuodogenes, arranged in long subtelomeric arrays (Figure 4.29). Because they are not adjacent to promoters, these genes cannot be directly expressed. Rather, they are first replicated and then the duplicate copy of the gene replaces the currently active VSG gene at the expression site. The pseudogene serving as a template remains in place. Thus, the pseudogenes are like a stored collection of genes that might be copied and subsequently expressed at any time. Both of these mechanisms occur following the transition to the blood-form trypomastigote, with the use of pseudogenes more likely to occur later, following the establishment of the chronic infection. This recombination appears to involve double-stranded breaks in the 70-base pair repeats, but the manner in which these breaks occur remains under investigation.
Genetic and genomic investigations
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Array CGH is the first genomic investigation to have been introduced into clinical practice on a wide scale since the karyotype, which it has largely replaced in many laboratories. The karyotype is still required for studies of specific chromosome rearrangements, such as inversions and reciprocal translocations, but array CGH is also replacing FISH and related investigations, such as searches for subtelomeric deletions.
Andrological causes of recurrent implantation failure
Published in Efstratios M. Kolibianakis, Christos A. Venetis, Recurrent Implantation Failure, 2019
Chrisanthi Marakaki, Georgios A. Kanakis, Dimitrios G. Goulis
Male chromosomal structural aberrations, such as translocation, inversion, and pericentric inversion, are also of particular concern.14 The development of locus-specific and subtelomeric DNA probes has allowed the analysis of chromosome segregation in carriers of inversions (pericentric and paracentric), Robertsonian translocations, and reciprocal translocations. These studies confirmed that carriers of structural chromosomal reorganizations produce chromosomally unbalanced sperm. If these gametes fertilize an oocyte, the resulting embryos, depending on the chromosome regions implicated, can give rise to abortions or offspring affected by chromosomal abnormalities.15 In addition, centrosome anomalies resulting in chaotic mosaics were most likely of paternal origin.16 It has been also proposed that balanced parental translocations may be implicated in the pathogenesis of implantation failure in IVF, and that genetic evaluation should be considered as part of the investigation of these couples.17 On the other hand, another large study by Rubio et al. analyzed the results of 131 ICSI cycles in couples with repeated abortion or implantation failure, in which the increased frequency of aneuploidy in spermatozoa did not affect the success of assisted reproductive techniques (ART).13
Ring chromosome 7 in a child with T-cell acute lymphoblastic leukemia with myeloid markers
Published in Baylor University Medical Center Proceedings, 2021
Carlos A. Tirado, Andrew Reyes, Wilson Yeh, Justin Yee, Joy King, Javier Kane, William Koss
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy resulting from the transformation and excessive proliferation of lymphoid T-cell progenitors. T-ALL accounts for 15% of all childhood cases of acute lymphoblastic leukemia (ALL) and 25% of all adult ALL cases, though the majority of T-ALL cases occur before age 40.1 Historically, T-ALL has been associated with poor clinical outcomes, but advances in intensified chemotherapy have raised pediatric and adult cure rates to over 80% and 50%, respectively.2 The presence of ring chromosomes (RCs) in T-ALL is rare, and as such their implications are not well understood within the context of this disease.3 We report a case of a girl diagnosed with T-ALL, in whom cytogenetics revealed the presence of ring 7 and deletions of the subtelomeric regions on chromosome 7.
The gene mutations and subtelomeric DNA methylation in immunodeficiency, centromeric instability and facial anomalies syndrome
Published in Autoimmunity, 2019
Haochang Hu, Chujia Chen, Shanping Shi, Bin Li, Shiwei Duan
The human subtelomeric region adjacent to the telomere is mainly composed of repeat sequences. Although the subtelomeres in human sperm and oocytes are almost not methylated, these regions are de novo methylated by DNMT3B during early embryonic development [15]. An abnormal telomere phenotype occurs when DNMT3B is mutated, indicating that subtelomeric methylation plays a key role in human telomere maintenance [16]. A growing body of studies has shown that subtelomeric DNA methylation plays a key role in many diseases [17]. During the development of liver cancer, the telomere length is prolonged, accompanied by hypomethylation of chromosome 7q subtelomeres and hypermethylation of chromosome 21q subtelomeres [18]. Patients with facioscapulohumeral muscular dystrophy (FSHD) 1 lost the D4Z4 macrosatellite repeat unit with high methylation and epigenetic silencing in the subtelomere region of the long arm in chromosome 4q [19,20].
Telomeres as a molecular marker of male infertility
Published in Human Fertility, 2019
Ewa Boniewska-Bernacka, Anna Pańczyszyn, Natalia Cybulska
Telomeres are nucleoprotein structures at the termini of eukaryotic cell chromosomes. The function of telomeres is to protect chromosomes from degradation and fusion (De Lange, 2005; Eisenstein, 2011; Podlevsky & Chen, 2012; Wysoczańska, 2013), spatial nucleus organization, and the regulation of transcription of genes located in subtelomeric regions (O’Sullivan & Karlseder, 2010). Telomeres also prevent chromosomal aberrations and ensure the proper course of recombination (De Lange, 2005; Suder et al, 2015). In humans, they consist of tandem repeats of (5′-TTAGGG-3′)n sequence occurring in a double-stranded cytosine-rich DNA fragment of 10–20 kb in length and guanine-rich single-stranded DNA of 50–300 bp (Aida et al., 2014; Lee et al., 2013; Muraki, Nyhan, Han, & Murnane, 2012). Telomeres comprise specialized Shelterin proteins: TRF1, TRF2, and POT1. TRF1 and TRF2 proteins exhibit high affinity for double-stranded repeated sequences (Draskovic & Vallejo, 2013; Neidle & Parkinson, 2003). The POT1 protein recognizes single-stranded guanine-rich repeats located at the 3′-end of telomeres. In the telosomal complex, TPP1, TIN2, and RAP1 proteins are also distinguished, which act as mediators between telomeric DNA-binding proteins (Muraki et al., 2012; Rode, Nordestgaard, Weischer, & Bojesen, 2014). The proteins: TANK, MRN, and Ku, which interact with proteins of the telosomal complex, also belong to telomeric proteins (Daniali et al., 2013; Moyzis et al., 1988).