Structural Chromosomal Changes Research Articles

Cytotaxonomy of Amaryllidaceae

Chromosome numbers are now known for about 46 genera in the family Amaryllidaceae. The lowest basic number has been found to be 5 and the' highest 30. Besides these two, 6, 7, 8, 9, 10, 11, 12, 14, 15, 16, 19, 23 and 29 have also been encountered of which 11 is found in majority of the genera. In a number of genera the derivation of one basic number from the other has been established. In the genus Allium largest number of species have been studied cytologically. The next largest is Narcissus followed by Zephyranthes, Crinum, Hippeastrum and Lycorisin that order.B or supernumerary chromosomes have been observed in Agapanthus, Allium, Crinum, Cooperia, Haemanthus, Hippeastrum, Lycoris and Narcissus.In this family repatterning of chromosomes through inversions (both para afid pericentric), translocation, polyploidy (eu-, aneuo-, hetero-, auto-, and allopolyploidy) and hybridization have played prominent role in chromosome number evolution, karyotype alteration and specisvtion. In addition to this, gene mutation has also played significant part in speciation. Ready vegetative propagation has helped in maintaining sterile hybrids and those forms with numerical and structural changes of chromosomes. Apomixis has also been responsible in chromosome number evolution in some genera.A consideration of taxonomic work done in Amaryllidaceae points out that Hutchinson's system of classification, based on the umbellate inflorescence rather than on the position of the ovary, has been found to be more phylogenetic but the amendments proposed by several workers for changes in tribal and generic level could be taken into consideration and in some cases may be justified.

Development, identification, and utilization of wheat-tetraploid Thinopyrum elongatum 4EL translocation lines resistant to stripe rust.

The new stripe rust resistance gene Yr4EL in tetraploid Th. elongatum was identified and transferred into common wheat via 4EL translocation lines. Tetraploid Thinopyrum elongatum is a valuable genetic resource for improving the resistance of wheat to diseases such as stripe rust, powdery mildew, and Fusarium head blight. We previously reported that chromosome 4E of the 4E (4D) substitution line carries all-stage stripe rust resistance genes. To optimize the utility of these genes in wheat breeding programs, we developed translocation lines by inducing chromosomal structural changes through 60Co-γ irradiation and developing monosomic substitution lines. In total, 53 plants with different 4E chromosomal structural changes were identified. Three homozygous translocation lines (T4DS·4EL, T5AL·4EL, and T3BL·4EL) and an addition translocation line (T5DS·4EL) were confirmed by the genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), FISH-painting, and wheat 55K SNP array analyses. These four translocation lines, which contained chromosome arm 4EL, exhibited high stripe rust resistance. Thus, a resistance gene (tentatively named Yr4EL) was localized to the chromosome arm 4EL of tetraploid Th. elongatum. For the application of marker-assisted selection (MAS), 32 simple sequence repeat (SSR) markers were developed, showing specific amplification on the chromosome arm 4EL and co-segregation with Yr4EL. Furthermore, the 4DS·4EL line could be selected as a good pre-breeding line that better agronomic traits than other translocation lines. We transferred Yr4EL into three wheat cultivars SM482, CM42, and SM51, and their progenies were all resistant to stripe rust, which can be used in future wheat resistance breeding programs.

Determining the degree of chromosomal instability in breast cancer cells by atomic force microscopy.

Chromosomal instability (CIN) is a source of genetic variation and is highly linked to the malignance of cancer. Determining the degree of CIN is necessary for understanding the role that it plays in tumor development. There is currently a lack of research on high-resolution characterization of CIN and the relationship between CIN and cell mechanics. Here, a method to determine CIN of breast cancer cells by high resolution imaging with atomic force microscopy (AFM) is explored. The numerical and structural changes of chromosomes in human breast cells (MCF-10A), moderately malignant breast cells (MCF-7) and highly malignant breast cells (MDA-MB-231) were observed and analyzed by AFM. Meanwhile, the nuclei, cytoskeleton and cell mechanics of the three kinds of cells were also investigated. The results showed the differences in CIN between the benign and cancer cells. Also, the degree of structural CIN increased with enhanced malignancy of cancer cells. This was also demonstrated by calculating the probability of micronucleus formation in these three kinds of cells. Meanwhile, we found that the area of the nucleus was related to the number of chromosomes in the nucleus. In addition, reduced or even aggregated actin fibers led to decreased elasticities in MCF-7 and MDA-MB-231 cells. It was found that the rearrangement of actin fibers would affect the nucleus, and then lead to wrong mitosis and CIN. Using AFM to detect chromosomal changes in cells with different malignancy degrees provides a new detection method for the study of cell carcinogenesis with a perspective for targeted therapy of cancer.

Chromosomal evolution in Cryptangieae Benth. (Cyperaceae): Evidence of holocentrism and pseudomonads.

Cryptangieae has recently been revised based on morphology and molecular phylogeny, but cytogenetic data is still scarce. We conducted this study with the aim of investigating the occurrence of holocentric chromosomes and pseudomonads, as well as understanding the mode of chromosomal evolution in the tribe. We performed analyses of meiotic behavior, chromosome counts, and reconstruction of the ancestral state for the haploid number. We present novel cytogenetic data for eight potentially holocentric species: Cryptangium verticillatum, Krenakia junciforme, K. minarum, Lagenocarpus bracteosus, L. griseus, L. inversus, L. rigidus, and L. tenuifolius. Meiotic abnormalities were observed, with parallel spindles being particularly noteworthy. Intra-specific variations in chromosome number were not found, which may indicate an efficient genetic control for the elimination of abnormal nuclei. The inferred ancestral haploid number was n = 16, with dysploidy being the main evolutionary mechanism. At least five chromosomal fissions occurred in Krenakia (n = 21), followed by a further ascending dysploidy event in Lagenocarpus (n = 17). As proposed for Cyperaceae, it is possible that cladogenesis events in Cryptangieae were marked by numerical and structural chromosomal changes.

A retrospective analysis of spontaneous chromosomal aberrations in human lymphocyte cultures of individuals from Bosnia and Herzegovina

Spontaneous chromosomal aberrations are structural or numerical changes of chromosomes that occur naturally, without exposure to external genotoxic factors. They are not inherited, occur randomly in the karyotype, and do not have direct clinical significance. However, they can affect genomic instability and disease predisposition. They can result from DNA replication or repair processes errors, and typically are observed in cells that are actively dividing. Spontaneous chromosomal aberrations may arise due to the natural chromosomal instability and can be elevated in individuals exposed to mutagens. We analyzed frequencies of spontaneous chromosomal aberrations in 137 individuals subjected to karyotype analysis at the Laboratory for Cytogenetics and Genotoxicology, University of Sarajevo – Institute for Genetic Engineering and Biotechnology, during 2008-2023. Whole blood samples were cultivated for 72 hours with the thymidine added in the 48th hour. Metaphases were arrested by colcemid 60 minutes before harvesting. GTG banding was performed and slides were analyzed under 1000x magnification in accordance with An International System for Human Cytogenetic Nomenclature and E.C.A. Cytogenetic Guidelines and Quality Assurance. Constitutionally aberrant karyotypes were found in 2.92% of analysed individuals as well as altered karyotypes considered as normal chromosomal variants. In the total of 3092 analyzed metaphases, 20 spontaneous chromosomal aberrations were found in 13 individuals. This study contributes to the limited knowledge of the cytogenetic status of the Bosnian and Herzegovinian population. Further monitoring of spontaneous chromosomal aberrations incidences is recommended.

Chromosome Banding and SNP-Array Analysis Are Complementary Methods to Characterize Karyotype Complexity in High-Risk Chronic Lymphocytic Leukemia

Introduction: Karyotype complexity is of prognostic significance in chronic lymphocytic leukemia (CLL). It can either be assessed by chromosome banding analysis (CBA) or by chromosome microarray analysis (CMA). How to integrate both methods into CLL diagnostic procedures is not defined. Material and Methods: To compare both methods in their ability to detect chromosomal aberrations, samples from 110 patients enrolled on the CLL2O trial (NCT01392079) were analyzed in parallel by Affymetrix ® 6.0 single nucleotide polymorphism arrays (SNP-arrays, CMA) and CBA (CpG oligonucleotide and IL-2 stimulation). The trial included genetically complex high-risk CLL cases defined by TP53 loss (treatment-naïve or relapsed) or refractoriness to purine-analogue based treatment. Intraindividual reference DNA for paired CMA was available for 79 samples. CMA-defined gains and losses outside known structural variations were counted as aberration irrespective of their size. Discontinuous gains and losses were counted as one aberration whenever segments had a similar log2-ratio. Results: CBA identified 561 chromosomal aberrations with a median of 4 aberrations per case (range: 0-21). With 653 DNA copy number alterations, CMA identified more aberrations partly afforded by a high number of unbalanced translocations (median: 5 aberrations per case, range: 0-19). With regards to karyotype complexity (KC), CBA and CMA allocated 67/110 cases (61%) to comparable risk groups as defined by Baliakas et al. (2019) and Leeksma et al. (2021). CMA assigned more cases to higher complexity risk groups than CBA, which was not observed when excluding gains and losses <5Mb not previously deemed to be significant. However, this approach did not improve the congruency in KC risk group stratification between both methods (see Table). Only 14/110 cases (13%) had a complete overlap in the chromosomes found to be affected by CBA and CMA. Overall, CBA discovered more additionally affected chromosomes than CMA (p=0.0104). Considering all localizable breakpoints of the CBA-defined structural chromosomal changes (N=922), 532 coincided with a cytoband or a cytoband directly adjacent to one harbouring CMA-defined copy number alterations (N=299 and N=233, respectively), whereas 128 CBA-defined breakpoints located to other cytobands on the same chromosome arm (N=85) or on the other arm (N=43). For 50 of these 128 breakpoints the distance between the CBA-identified cytoband and the CMA-defined breakpoint was <20 Mb. About one quarter of CBA-defined breakpoints (N=237, 23%) affected chromosomes not found to be altered in CMA. Potential explanations for non-detection by CMA were small clone sizes (78/237, 33%; considering breakpoints found in <25% of metaphases), association with an ultra-complex karyotype (140/237, 59%; referring to cases with ≥10 affected chromosomes and/or a composite karyotype), and no or poor coverage of cytobands by SNP-array probes (72/237, 30%; referring to cytobands with stretches >1Mb covered by ≤5 probes). Besides, the vast majority of the 237 breakpoints belonged to alterations that can in principle be balanced: 209 translocations, 8 insertions and 2 inversions. Only 18/237 breakpoints defined deletions, 15 of which met at least one of the criteria mentioned above as potential explanations for non-detection by CMA. Overall, 134 chromosomal alterations were detected by CMA alone. Four of these alterations were copy neutral losses of heterozygosity. Most of the 130 DNA copy number alterations were <20 Mb in size (N=104) and 22/130 alterations have previously been associated with a shorter overall survival (affecting 18/110 cases; 16%). Regarding loss of CDKN2A/ B and gain of MYC as genetic features associated with an increased risk for Richter transformation, CMA identified three cases each lacking abnormalities on the respective chromosome in CBA. CBA identified three cases with a potential MYC rearrangement and one case with a potential CDKN2A/ B loss despite having normal results for 9p21 in CMA. Conclusions: In this cohort of high-risk CLL cases, CBA and CMA were complementary methods for karyotype characterization. CBA was more sensitive in uncovering chromosome involvement than CMA, whereas CMA was superior in determining specific DNA copy number alterations previously associated with an inferior prognosis. As to what extend these findings apply to standard-risk CLL cases needs to be investigated.

BIRC5 Inhibition Is Associated with Pyroptotic Cell Death via Caspase3-GSDME Pathway in Lung Adenocarcinoma Cells.

Lung adenocarcinoma (LUAD) is a prevalent type of thoracic cancer with a poor prognosis and high mortality rate. However, the exact pathogenesis of this cancer is still not fully understood. One potential factor that can contribute to the development of lung adenocarcinoma is DNA methylation, which can cause changes in chromosome structure and potentially lead to the formation of tumors. The baculoviral IAP repeat containing the 5 (BIRC5) gene encodes the Survivin protein, which is a multifunctional gene involved in cell proliferation, migration, and invasion of tumor cells. This gene is elevated in various solid tumors, but its specific role and mechanism in lung adenocarcinoma are not well-known. To identify the potential biomarkers associated with lung adenocarcinoma, we screened the methylation-regulated differentially expressed genes (MeDEGs) of LUAD via bioinformatics analysis. Gene ontology (GO) process and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to investigate the biological function and pathway of MeDEGs. A protein-protein interaction (PPI) network was employed to explore the key module and screen hub genes. We screened out eight hub genes whose products are aberrantly expressed, and whose DNA methylation modification level is significantly changed in lung adenocarcinoma. BIRC5 is a bona fide marker which was remarkably up-regulated in tumor tissues. Flow cytometry analysis, lactate dehydrogenase release (LDH) assay and Micro-PET imaging were performed in A549 cells and a mouse xenograft tumor to explore the function of BIRC5 in cell death of lung adenocarcinoma. We found that BIRC5 was up-regulated and related to a high mortality rate in lung adenocarcinoma patients. Mechanically, the knockdown of BIRC5 inhibited the proliferation of A549 cells and induced pyroptosis via caspase3/GSDME signaling. Our findings have unraveled that BIRC5 holds promise as a novel biomarker and therapeutic target for lung adenocarcinoma. Additionally, we have discovered a novel pathway in which BIRC5 inhibition can induce pyroptosis through the caspase3-GSDME pathway in lung adenocarcinoma cells.

Chromosomal instability-induced cell invasion through caspase-driven DNA damage

Chromosomal instability (CIN), an increased rate of changes in chromosome structure and number, is observed in most sporadic human carcinomas with high metastatic activity. Here, we use a Drosophila epithelial model to show that DNA damage, as a result of the production of lagging chromosomes during mitosis and aneuploidy-induced replicative stress, contributes to CIN-induced invasiveness. We unravel a sub-lethal role of effector caspases in invasiveness by enhancing CIN-induced DNA damage and identify the JAK/STAT signaling pathway as an activator of apoptotic caspases through transcriptional induction of pro-apoptotic genes. We provide evidence that an autocrine feedforward amplification loop mediated by Upd3-a cytokine with homology to interleukin-6 and a ligand of the JAK/STAT signaling pathway-contributes to amplifying the activation levels of the apoptotic pathway in migrating cells, thus promoting CIN-induced invasiveness. This work sheds new light on the chromosome-signature-independent effects of CIN in metastasis.

Brain Tumor : Molecular Biology, Pathophysiology, and Clinical Symptoms

Brain tumors are one of the most malignant tumors that occur in humans. It accounts for approximately 1.35% of all malignant neoplasms and 29.5% of cancer deaths. This article was written with the aim of knowing more about molecular biology, phatophysiology, and clinical symptoms of brain tumor. The method used is a literature review combined with a search for related sources from National Center for Biotechnology Information (NCBI), Google Scholar, and Research Gate. The results of this literature review of the articles carried out can be concluded that brain tumors often cause symptoms of physiological disorders, such as focal signs, fatigue and headaches or behavioral disorders including hallucinations, depression, anxiety, decreased attention and awareness. Brain tumors can also arise spontaneously without a family history or previous genetic inheritance pattern. In conclusion, cytogenetic and molecular abnormalities in brain tumors can be seen in numerical and structural chromosomal changes, gene amplification and overexpression, deletions and small-scale mutations and epigenetic deregulation.

Meiotic behavior of two grapevine somatic mutants with ornamental potential

‘Niagara Steck’ and ‘Niagara Variegada’ are two grapevine varieties that arose spontaneously as somatic mutants of ‘Niagara Rosada’. Berries characterize ‘Niagara Steck’ at young stages exhibiting a remarkable brown reticulated structure on the epidermis which develops into a brown-bronze russet-like structure as the berries ripe. The mature berries have strongly acidic flesh. ‘Niagara Variegada’ shows notable variegation in leaves and berries. Meiotic studies were carried out to ascertain if the mutant phenotypes could be related to any change in chromosome number, structure or other irregularity. Floral buds of both varieties at different developmental stages were collected and fixed for cytological analyses. Chromosome counts at diakinesis/metaphase I showed n=19 bivalents for both varieties. Univalent, trivalent, tetravalent chromosomes or chain configuration were not recorded ruling out the possibility of any alteration in the chromosome number or structure in both mutant varieties. However, low percentages of meiotic irregularities were recorded such as chromosome stickiness, laggards, non-oriented chromosomes, precocious chromosome segregation, tetrads with one microcyte, microspore fusion, and tetrad degeneration. The total percentage of abnormalities was higher in ‘Niagara Variegada’ (19.68%) than in ‘Niagara Steck’ (14.40%) which may have contributed to a lower percentage of pollen fertility (79.80%) when compared to ‘Steck’ (90.74%). The aforementioned varieties can be propagated by hardwood cuttings and constitute an interesting option for ornamentation of home backyards, patios, and gardens with the advantage that ‘Niagara Variegada’ bearing sweet edible berries.

Meiotic DNA double-strand break-independent role of protein phosphatase 4 in Hop1 assembly to promote meiotic chromosome axis formation in budding yeast.

Dynamic changes in chromosomal structure that occur during meiotic prophase play an important role in the progression of meiosis. Among them, meiosis-specific chromosomal axis-loop structures are important as a scaffold for integrated control between the meiotic recombination reaction and the associated checkpoint system to ensure accurate chromosome segregation. However, the molecular mechanism of the initial step of chromosome axis-loop construction is not well understood. Here, we showed that, in budding yeast, protein phosphatase 4 (PP4) that primarily counteracts Mec1/Tel1 phosphorylation is required to promote the assembly of a chromosomal axis component Hop1 and Red1 onto meiotic chromatin via interaction with Hop1. PP4, on the other hand, less affects Rec8 assembly. Notably, unlike the previously known function of PP4, this PP4 function in Hop1/Red1 assembly was independent of meiotic DSB-dependent Tel1/Mec1 kinase activities. The defect in Hop1/Red1 assembly in the absence of PP4 function was not suppressed by dysfunction of Pch2, which removes Hop1 protein from the chromosome axis, suggesting that PP4 is required for the initial step of chromatin loading of Hop1 rather than stabilization of Hop1 on axes. These results indicate phosphorylation/dephosphorylation-mediated regulation of Hop1 recruitment onto chromatin during chromosome axis construction before meiotic double-strand break formation.

Paths to adaptation under fluctuating nitrogen starvation: The spectrum of adaptive mutations in Saccharomyces cerevisiae is shaped by retrotransposons and microhomology-mediated recombination.

There are many mechanisms that give rise to genomic change: while point mutations are often emphasized in genomic analyses, evolution acts upon many other types of genetic changes that can result in less subtle perturbations. Changes in chromosome structure, DNA copy number, and novel transposon insertions all create large genomic changes, which can have correspondingly large impacts on phenotypes and fitness. In this study we investigate the spectrum of adaptive mutations that arise in a population under consistently fluctuating nitrogen conditions. We specifically contrast these adaptive alleles and the mutational mechanisms that create them, with mechanisms of adaptation under batch glucose limitation and constant selection in low, non-fluctuating nitrogen conditions to address if and how selection dynamics influence the molecular mechanisms of evolutionary adaptation. We observe that retrotransposon activity accounts for a substantial number of adaptive events, along with microhomology-mediated mechanisms of insertion, deletion, and gene conversion. In addition to loss of function alleles, which are often exploited in genetic screens, we identify putative gain of function alleles and alleles acting through as-of-yet unclear mechanisms. Taken together, our findings emphasize that how selection (fluctuating vs. non-fluctuating) is applied also shapes adaptation, just as the selective pressure (nitrogen vs. glucose) does itself. Fluctuating environments can activate different mutational mechanisms, shaping adaptive events accordingly. Experimental evolution, which allows a wider array of adaptive events to be assessed, is thus a complementary approach to both classical genetic screens and natural variation studies to characterize the genotype-to-phenotype-to-fitness map.

Intraspecific divergence of diploid grass Aegilopscomosa is associated with structural chromosome changes.

Aegilopscomosa Smith in Sibthorp et Smith, 1806 is diploid grass with MM genome constitution occurring mainly in Greece. Two morphologically distinct subspecies - Ae.c.comosa Chennaveeraiah, 1960 and Ae.c.heldreichii (Holzmann ex Boissier) Eig, 1929 are discriminated within Ae.comosa, however, genetic and karyotypic bases of their divergence are not fully understood. We used Fluorescence in situ hybridization (FISH) with repetitive DNA probes and electrophoretic analysis of gliadins to characterize the genome and karyotype of Ae.comosa to assess the level of their genetic diversity and uncover mechanisms leading to radiation of subspecies. We show that two subspecies differ in size and morphology of chromosomes 3M and 6M, which can be due to reciprocal translocation. Subspecies also differ in the amount and distribution of microsatellite and satellite DNA sequences, the number and position of minor NORs, especially on 3M and 6M, and gliadin spectra mainly in the a-zone. Frequent occurrence of hybrids can be caused by open pollination, which, along with genetic heterogeneity of accessions and, probably, the lack of geographic or genetic barrier between the subspecies, may contribute to extremely broad intraspecific variation of GAAn and gliadin patterns in Ae.comosa, which are usually not observed in endemic plant species.

Abstract 1185: Mosaic chromosomal alterations are independent predictors of chronic lymphocytic leukemia risk

Abstract Chronic lymphocytic leukemia (CLL) is strongly associated with mosaic chromosomal alterations (mCAs), a type of clonal hematopoiesis characterized by large structural chromosomal changes (e.g., gains, losses and copy neutral loss of heterozygosity). We aim to identify specific chromosomal regions that, when impacted by mCAs, are most predictive of CLL risk and evaluate their predictive utility in models that include established CLL risk factors. We utilized genotype array data from 436,784 participants in the UK Biobank (UKBB) and 35,382 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial to identify mCAs. UKBB was split (90/10) into training and test sets, and PLCO served as an external validation set. We developed sequential regression models to predict risk of CLL, with a baseline model consisting of age, age-squared, sex, smoking status, and ancestry. Additional models evaluated mCAs, a CLL polygenic risk score (PRS), and blood cell counts. Area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive utility for both 5-year and 10-year CLL risk. Any detectable mCA was associated with incident CLL (Hazards Ratio (HR)=26, 95% Confidence interval (CI)=21-31), and mCAs on each individual chromosome were associated with increased CLL risk. mCAs on segments of chromosomes 13, 12, 22, 14, and 11 had the largest effect size (e.g., chr 13q14 HR=199, 95%CI=155-257). The CLL prediction model, including baseline factors, CLL PRS, and any autosomal mCA status, showed strong predictive utility in independent UKBB (AUC=0.88) and PLCO (AUC=0.88) samples. Restricting to a subset of mCAs strongly associated with CLL did not improve performance over including any detectable autosomal mCA. After the inclusion of blood cell traits, predictive utility further increased in UKBB (AUC=0.91; no count data available in PLCO). We observed the strongest CLL predictive utility in 5-year risk compared to 10-year risk across all models. mCAs genome-wide are associated with CLL risk, with variable effects across chromosomes and specific chromosomal regions. Autosomal mCAs are strong independent predictors of CLL risk and substantially add to predictive utility over standard clinical measures. The predictive utility of autosomal mCAs is strongest within the first 1-5 years of sample collection. Evaluation of mCAs could provide added utility for risk stratification in populations at high risk of CLL. Citation Format: Aubrey K. Hubbard, Alexander DePaulis, Sruthi Srinivasan, Ian D. Buller, Shu-Hong Lin, Weiyin Zhou, Stephen J. Chanock, Neal D. Freedman, Derek W. Brown, Mitchell J. Machiela. Mosaic chromosomal alterations are independent predictors of chronic lymphocytic leukemia risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1185.

Structural changes in chromosomes driven by multiple condensin motors during mitosis

We create a computational framework that utilizes loop extrusion (LE) by multiple condensin I/II motors to predict changes in chromosome organization during mitosis. The theory accurately reproduces the experimental contact probability profiles for the mitotic chromosomes in HeLa and DT40 cells. The LE rate is smaller at the start of mitosis and increases as the cells approach metaphase. Condensin II-mediated mean loop size is about six times larger than loops because of condensin I. The loops, which overlap each other, are stapled to a central dynamically changing helical scaffold formed by the motors during the LE process. A polymer physics-based data-driven method that uses the Hi-C contact map as the only input shows that the helix is characterized as random helix perversions (RHPs) in which the handedness changes randomly along the scaffold. The theoretical predictions, which are testable using imaging experiments, do not contain any parameters.

Effect of Female Age on Crossing Over Frequency in Drosophila melanogaster Crosses N x bcl and N x ym and Their Reciprocals

Crossing over is the occurrence of disconnection and reconnection followed by a reciprocal exchange between the two chromatids in a bivalent form. The crossing event will produce parental type and recombinant type. In the event of crossing over, various factors can influence it. These factors can be due to internal and external. Recently, various factors have been reported that influence the incidence of crossing over. These factors include age, temperature, radiation, and changes in chromosome structure. This research is a type of experimental research that uses a randomized block design. Randomized block design by crossing D. melanogaster strains ?N>< ?bcl and ?N>< ?ym and their reciprocals. From the results of this cross (F1) then cross again ?N with the recessive male (from stock) then observe the phenotype of the offspring (F2) and calculate the results of the offspring. The F2 ?N crosses were treated with age variations, namely 0, 3, 6, 9, 12, 15, and 18 days. Based on the results of these crosses, the derived strains that appeared in the F2 crosses showed the phenomenon of crossing over with the influence of the age of the female and the type of strain on crossing events. the frequency or value of crossing over (formation of recombinants) decreased with the increasing age of the female. If the age of the female affects the frequency of crossing over, then the older the female, the more likely the frequency of crossing over will decrease. However, because the data obtained were incomplete, it was not possible to know the effect of female age on the frequency of crossing over of D. melanogaster crosses ?N>< ? bcl and ?N >< ?ym and their reciprocals. The condition for crossing over is the formation of a synaptonemal complex. Age of D. melanogaster females has an effect on the frequency of crossing over in crosses N? >< bcl?, N? >< ym?, and their reciprocals. The older Drosophila melanogaster is, the lower the frequency of crossing over will occur. Based on this, it was necessary to cross D. melanogaster with strains N, bcl, and ym. A cross consists of ?N ><?bcl and ?N ><?ym and their reciprocals. By crossing ?N with a recessive male from the stock, then observing the F2 phenotype, it is hoped that crossing over will occur. So that you can better understand by doing the practice directly. In this case, the effect of crossing over is seen from the age of the female and the type of strain.

Genomic rearrangements and evolutionary changes in 3D chromatin topologies in the cotton tribe (Gossypieae)

BackgroundAnalysis of the relationship between chromosomal structural variation (synteny breaks) and 3D-chromatin architectural changes among closely related species has the potential to reveal causes and correlates between chromosomal change and chromatin remodeling. Of note, contrary to extensive studies in animal species, the pace and pattern of chromatin architectural changes following the speciation of plants remain unexplored; moreover, there is little exploration of the occurrence of synteny breaks in the context of multiple genome topological hierarchies within the same model species.ResultsHere we used Hi-C and epigenomic analyses to characterize and compare the profiles of hierarchical chromatin architectural features in representative species of the cotton tribe (Gossypieae), including Gossypium arboreum, Gossypium raimondii, and Gossypioides kirkii, which differ with respect to chromosome rearrangements. We found that (i) overall chromatin architectural territories were preserved in Gossypioides and Gossypium, which was reflected in their similar intra-chromosomal contact patterns and spatial chromosomal distributions; (ii) the non-random preferential occurrence of synteny breaks in A compartment significantly associate with the B-to-A compartment switch in syntenic blocks flanking synteny breaks; (iii) synteny changes co-localize with open-chromatin boundaries of topologically associating domains, while TAD stabilization has a greater influence on regulating orthologous expression divergence than do rearrangements; and (iv) rearranged chromosome segments largely maintain ancestral in-cis interactions.ConclusionsOur findings provide insights into the non-random occurrence of epigenomic remodeling relative to the genomic landscape and its evolutionary and functional connections to alterations of hierarchical chromatin architecture, on a known evolutionary timescale.

Clonal hematopoiesis due to mosaic chromosomal alterations: Impact on disease risk and mortality

Mosaic chromosomal alterations (mCAs) are the clonal expansion of large somatically acquired structural chromosomal changes present on the autosomes and sex chromosomes. Most studies of mCAs use existing genotype array intensity data from large populations to investigate potential risk factors and disease outcomes associated with mCAs. In this review, we perform a comprehensive examination of existing evidence for mCA disease and mortality associations and provide a framework for interpreting these associations in the context of important biases specific to mCA studies. Our goal is to motivate well-designed mCA studies to assist in unlocking the potential of mCAs to improve understanding of the effects of ageing and accelerate translational applications for improving public health.

Extranodal Marginal Zone Lymphomas Show Recurrent Mutations in DNA Repair Genes, Cancer-Associated Proliferative Signaling and NOTCH1 Signaling Pathways, Regardless of Anatomic Site

Extranodal marginal zone lymphomas (EMZL) are usually indolent B cell lymphomas arising in acquired mucosa-associated lymphoid tissue (MALT) as a result of chronic antigen stimulation from infection or autoimmune processes. EMZLs occurring at different MALT sites have shared and unique genetic events including site-associated chromosomal structural changes and mutations. While large scale genetic analyses of EMZL are lacking, previous small studies have shown that EMZL often show activation of NF-κB through chronic stimulation of the B cell receptor and other cooperating genetic events that include somatic mutations, most frequently in TNFAIP3. Here, we report the largest whole exome sequencing (WES) and copy number (CN) analysis to date in EMZL. Formalin-fixed paraffin-embedded (FFPE) samples of EMZL were collected as part of the Atlas of Blood Cancer Genomes (ABCG) consortium. All cases underwent central pathology review by expert hematopathologists and diagnoses were confirmed as defined by the 2016 WHO classification. We defined global CN gains and losses at log2 fold change value of ±0.3, a value used by many CN tools. DNA and RNA WES were performed using the Illumina platform and DNA and RNA reads aligned to the GRCh38 genome and transcriptome, respectively. Exonic variants were identified and filtered using normal samples and population-based databases to identify putative driver mutations which were then aggregated at the gene level. Mutational analysis was done on samples that passed quality filtering. 225 unique diagnostic specimens were collected from 24 academic hematopathology departments. Cases originated from North America (USA and Canada, 86%), Europe (8%), and Asia (Singapore and China, 6%). 72 tumors were excluded due to inadequate mean coverage related to size of the biopsy or its quality. CN analysis and WES to identify non-silent mutations was performed in 153 unique EMZL including ocular adnexal (31), stomach (26), lung (23), salivary gland (23), and other extranodal locations (50). Average patient age was 63 years (range 53-71 years), female: male ratio of 1.6. Mutation calls identified 718 variants (613 missense mutations and 105 truncating mutations) across 59 putative driver genes detected in ≥5% cases across all the anatomic locations. Among the most commonly mutated genes, we detected genes previously reported to be altered by targeted sequencing in EMZL (e.g., SPEN (12%), TNFAIP3 (A20) (8%), CREBBP (8%), TBL1XR1 (7%), and others) confirming our filtering strategy. A total of 44 focal CN alterations (24 gains and 20 CN losses) were detected for our set of recurrently mutated genes. Global CN gains included chromosome 3 (6%), 6p (7%), 8 (3%), 12 (4%), and 18 (5%) and losses in 21p (10%). Previously described tumor suppressor genes such as TNFAIP3 showed a typical pattern of alterations consisting of CN losses (6q23.3 deletion in 6%) and/or mostly truncating mutations (8%). Combining DNA mutations and CN alterations, the number of genetic lesions per tumor sample in the 59 putative driver genes ranged from 1 to 21, with an average load of 4.9 aberrations per case, consistent with previous genetic studies in other types of MZL lymphoma. The most frequent mutations across all sites were IGLL5 (22%), KMT2C (15%), KMT2D (14%), SPEN (12%), PRDM2 (11%), and NCOR1 (10%). Analysis using Elsevier Pathway Collection, BioPlanet 2019 and Go Biological Process 2021 revealed adjusted statistically significant enrichment of aberrations in genes in NOTCH signaling, DNA repair, cancer-associated sustaining of proliferative signaling, cancer associated histone methylation and positive regulation of transcription, by DNA-templated (GO:0045893) and RNA polymerase II (GO:0045944). Many of the mutated genes were previously not reported in EMZL. Some of the mutations were shared by tumors at different anatomic locations while some were more unique. Mutations in TET2, previous reported as specific for thyroid EMZL, were also detected in ocular adnexa, gastric and salivary gland MZL. Mutations in PTPRD, previously suggested as specific for NMZL, were detected also in EMZL. Overall, this analysis of a large number of samples from different anatomic locations further refines the mutational landscape in EMZL and provides novel clues on pathogenesis. More detailed analyses of mutations, CN variations and RNA expression will be presented at the meeting.

Current Molecular Profile of Gastrointestinal Stromal Tumors and Systemic Therapeutic Implications.

Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising from the intestinal pacemaker cells of Cajal. They compose a heterogenous group of tumors due to a variety of molecular alterations. The most common gain-of-function mutations in GISTs are either in the KIT (60-70%) or platelet-derived growth factor receptor alpha (PDGFRA) genes (10-15%), which are mutually exclusive. However, a smaller subset, lacking KIT and PDGFRA mutations, is considered wild-type GISTs and presents distinct molecular findings with the activation of different proliferative pathways, structural chromosomal and epigenetic changes, such as inactivation of the NF1 gene, mutations in the succinate dehydrogenase (SDH), BRAF, and RAS genes, and also NTRK fusions. Currently, a molecular evaluation of GISTs is imperative in many scenarios, aiding in treatment decisions from the (neo)adjuvant to the metastatic setting. Here, we review the most recent data on the molecular profile of GISTs and highlight therapeutic implications according to distinct GIST molecular subtypes.