Structural Chromosomal Changes Research Articles

SRSF2 Mutations in Uveal Melanoma: A Preference for In-Frame Deletions?

Background: Uveal melanoma (UM) is the most common primary ocular malignancy in adults in the Western world. UM with a mutation in SF3B1, a spliceosome gene, is characterized by three or more structural changes of chromosome 1, 6, 8, 9, or 11. Also UM without a mutation in SF3B1 harbors similar chromosomal aberrations. Since, in addition to SF3B1, mutations in U2AF1 and SRSF2 have also been observed in hematological malignancies, UM without a SF3B1 mutation—but with the characteristic chromosomal pattern—might harbor mutations in one of these genes. Methods: 42 UMs were selected based on their chromosomal profile and wildtype SF3B1 status. Sanger sequencing covering the U2AF1 (exon 2 and 7) hotspots and SRSF2 (exon 1 and 2) was performed on DNA extracted from tumor tissue. Data of three UM with an SRSF2 mutation was extracted from the The Cancer Genome Atlas (TCGA). Results: Heterozygous in-frame SRSF2 deletions affecting amino acids 92–100 were detected in two UMs (5%) of 42 selected tumors and in three TGCA UM specimens. Both the UM with an SRSF2 mutation from our cohort and the UM samples from the TCGA showed more than four structural chromosomal aberrations including (partial) gain of chromosome 6 and 8, although in two TCGA UMs monosomy 3 was observed. Conclusions: Whereas in myelodysplastic syndrome predominantly missense SRSF2 mutations are described, the observed SRSF2 mutations in UM are all in-frame deletions of 8–9 amino acids. This suggests that the R625 missense SF3B1 mutations and SRSF2 mutations in UM are different compared to the spliceosome gene mutations in hematological cancers, and probably target a different, as yet unknown, set of genes involved in uveal melanoma etiology.

Frequency and types of chromosomal abnormalities in acute lymphoblastic leukemia patients in Turkey

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and is usually associated with numerical and structural chromosomal changes.

Karyological traits related to phylogenetic signal and environmental conditions within the Hymenaea clade (Leguminosae, Detarioideae)

The Hymenaea clade is a lineage of the subfamily Detarioideae of Leguminosae. The clade is currently composed of three genera: Guibourtia, Hymenaea, and Peltogyne. The genera Guibourtia and Hymenaea present an Amphi-Atlantic distribution, whereas Peltogyne is exclusively found in the Neotropics. Previous studies have focused on the phylogeny of the group but there are no studies that demonstrate mechanisms that could be involved in the evolution of this Amphi-Atlantic clade. The present work is the largest cytogenetic analysis for the group published so far. We aimed to provide a study of karyotypic characteristics of the Hymenaea clade, interpreted using the plastidial trnK phylogenetic reconstruction as background. We analyzed karyological characteristics such as chromosome number, chromosome size, centromeric position, CMA/DAPI patterns, and banding for 5S and 45S rDNA. With the present data available, multivariate analyses (PCA) and Phylogenetic Eigenvector Regression (PVR) demonstrated that centromeric asymmetry and number of 5S rDNA sites may present a strong phylogenetic signal, whereas number of CMA+ sites is associated with geography/climate characteristics. The association of CMA bands and geography has been reported for other legumes of the Caesalpinia group. This study demonstrates that the use of statistical tools for analyzing karyotypic characteristics can result in more precise interpretation of evolutionary processes related to structural changes in chromosomes and how these changes can also be related to environmental conditions.

Effect of lead on polytenic chromosomes from salivary glands of Chironomus Plumosus L. and Glyptotendipes Glaucus Mg. (Diptera, Chironomidae)

Background. Experimental conditions allow to determine the structural and functional changes of polytene chromosomes under the influence of free ions of an individual metal.
 Materials and methods. C. plumosus (L.) and G. glaucus (Mg) larvae were placed in solutions of lead nitrate: 0.01, 0.02, 0.1 and 0.5 mg/l. Exposure 12 h. Analysis of preparations of polytene chromosomes was carried out using the Carl Zeiss PrimoStar microscope. The functional activity factor of the nucleolus organizer (NOR), the coefficient of genetic activity of the Balbiani ring (BRR) was calculated.
 Results. Equations of the dependence of the change in the coefficients: NOR = 5,1870,01 lnC for C. plumosus and NOR = 2,110,03 lnC for G. glaucus; BRR = 1,5040,04 lnC for C. plumosus and BRR = 2,018 + 0,03 lnC for G. glaucus.
 Conclusion. With an increase in the concentration of lead in both C. plumosus and G. glaucus decreases NOR, which implies a decrease in the intensity of protein biosynthesis processes. BRR decreases in C. plumosus and increases in G. glaucus. The different genome reactions of the two species indicate the existence of different mechanisms of adaptation to lead ions

DNA methylation profiling reliably distinguishes pulmonary enteric adenocarcinoma from metastatic colorectal cancer

Pulmonary enteric adenocarcinoma is a rare non-small cell lung cancer subtype. It is poorly characterized and cannot be distinguished from metastatic colorectal or upper gastrointestinal adenocarcinomas by means of routine pathological methods. As DNA methylation patterns are known to be highly tissue specific, we aimed to develop a methylation-based algorithm to differentiate these entities. To this end, genome-wide methylation profiles of 600 primary pulmonary, colorectal, and upper gastrointestinal adenocarcinomas obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database were used as a reference cohort to train a machine learning algorithm. The resulting classifier correctly classified all samples from a validation cohort consisting of 680 primary pulmonary, colorectal and upper gastrointestinal adenocarcinomas, demonstrating the ability of the algorithm to reliably distinguish these three entities. We then analyzed methylation data of 15 pulmonary enteric adenocarcinomas as well as four pulmonary metastases and four primary colorectal adenocarcinomas with the algorithm. All 15 pulmonary enteric adenocarcinomas were reliably classified as primary pulmonary tumors and all four metastases as well as all four primary colorectal cancer samples were identified as colorectal adenocarcinomas. In a t-distributed stochastic neighbor embedding analysis, the pulmonary enteric adenocarcinoma samples did not form a separate methylation subclass but rather diffusely intermixed with other pulmonary cancers. Additional characterization of the pulmonary enteric adenocarcinoma series using fluorescence in situ hybridization, next-generation sequencing and copy number analysis revealed KRAS mutations in nine of 15 samples (60%) and a high number of structural chromosomal changes. Except for an unusually high rate of chromosome 20 gain (67%), the molecular data was mostly reminiscent of standard pulmonary adenocarcinomas. In conclusion, we provide sound evidence of the pulmonary origin of pulmonary enteric adenocarcinomas and in addition provide a publicly available machine learning-based algorithm to reliably distinguish these tumors from metastatic colorectal cancer.

Comet Assay and Applications

Currently, humans and other living things can have many genotoxic damages due to reasons such as chemicals, drugs, unfavorable environmental effects. Breaks in the DNA structure due to genotoxic damage can cause mutations, changes in chromosome structure and cancer. Comet assay, also known as a single cell gel electrophoresis (SCGE), is a sensitive, rapid and cheap method used to measure DNA damage and repair at the individual cell level. With this method, cells are called this way because of they appear as comets under a microscope. DNA damage and repair can be detected in each cell type that can be obtained as single cell suspension, with comet assay. In addition to the direct determination of DNA damage in a single cell, it is possible to determine whether all cells in a population suffer from the same amount of damage. Furthermore, this assay may help to predict the heterogeneous response of cells during any treatment, and the tumor response in radiotherapy and chemotherapy treatment protocols. Especially in human biomonitoring studies, it is also used in the investigation of DNA damage in people who exposed to various occupational or accident-related environmental or workplace-related agents. In this review, a general overview of the comet assay and its currently applications to determine the genotoxicity of environmental factors and chemicals are discussed. Key words : DNA damage, DNA repair, genotoxicity, comet assay, single cell gel electrophoresis. DOI : 10.7176/JSTR/5-5-02

Meiosis, spermatogenesis and ultrastructure of the basement membrane of seminiferous tubules in patients with azoospermia

The study objective is to determine the connection between meiosis abnormalities and changes in the basement membrane (BM) ultrastructure of the seminiferous tubules in patients with spermatogenesis disorders: azoospermia or severe oligospermia. Materials and methods. Electron microscopy of BMstructure of the seminiferous tubules of 31 patients with azoospermia or severe oligospermia and normal male karyotype (46, XY) without microdeletions of the Y chromosome or structural changes in chromosomes was performed. The group 1 included 18 patients with preserved spermatogenesis including germinal cell differentiation into mature spermatids; the group 2 consisted of13 patients with either Sertoli cells and spermatogonia or only Sertoli cells. Results. Six main types of ultrastructural changes in BM were observed. The most prominent were BM invaginations in the form of basket weaves that were observed in 8 of 13patients in the group 2. In the group 1, individual basket weaves were observed in 2 of 18patients. Im-munocytochemical examination of I order spermatocyte spread nuclei in 14 patients was performed. In patients of the group 2, spermatocytes weren’t discovered. In 10 patients of the group 1, meiosis arrest at the zygotene and pachytene stages was observed in 18—50 % of spermatocytes. In 6patients, 30 to 50 % of spermatocytes with impaired formation of the structure of the sex body were revealed. Conclusion . The morphological changes of the BM of the seminiferous tubules (“basket weaves” and duplications of the BM) are associated with marked disorders of meiosis and spermatogenesis. It is suggested about the possibility of mutations of the genes encoding the proteins of BM.

Impact of Chromosomal Rearrangements on the Interpretation of Lupin Karyotype Evolution.

Plant genome evolution can be very complex and challenging to describe, even within a genus. Mechanisms that underlie genome variation are complex and can include whole-genome duplications, gene duplication and/or loss, and, importantly, multiple chromosomal rearrangements. Lupins (Lupinus) diverged from other legumes approximately 60 mya. In contrast to New World lupins, Old World lupins show high variability not only for chromosome numbers (2n = 32–52), but also for the basic chromosome number (x = 5–9, 13) and genome size. The evolutionary basis that underlies the karyotype evolution in lupins remains unknown, as it has so far been impossible to identify individual chromosomes. To shed light on chromosome changes and evolution, we used comparative chromosome mapping among 11 Old World lupins, with Lupinus angustifolius as the reference species. We applied set of L. angustifolius-derived bacterial artificial chromosome clones for fluorescence in situ hybridization. We demonstrate that chromosome variations in the species analyzed might have arisen from multiple changes in chromosome structure and number. We hypothesize about lupin karyotype evolution through polyploidy and subsequent aneuploidy. Additionally, we have established a cytogenomic map of L. angustifolius along with chromosome markers that can be used for related species to further improve comparative studies of crops and wild lupins.

Regeneration of Solanum tuberosum Plants from Protoplasts Induces Widespread Genome Instability.

Nontransgenic genome editing in regenerable protoplasts, plant cells free of their cell wall, could revolutionize crop improvement because it reduces regulatory and technical complexity. However, plant tissue culture is known to engender frequent unwanted variation, termed somaclonal variation. To evaluate the contribution of large-scale genome instability to this phenomenon, we analyzed potatoes (Solanum tuberosum) regenerated from either protoplasts or stem explants for copy number changes by comparison of Illumina read depth. Whereas a control set of eight plants that had been propagated by cuttings displayed no changes, all 15 protoplast regenerants tested were affected by aneuploidy or structural chromosomal changes. Certain chromosomes displayed segmental deletions and duplications ranging from one to many. Resampling different leaves of the same plant found differences in three regenerants, indicating frequent persistence of instability. By comparison, 33 regenerants from stem explants used for Agrobacterium-mediated transformation displayed less frequent but still considerable (18%) large-scale copy number changes. Repetition of certain instability patterns suggested greater susceptibility in specific genomic sites. These results indicate that tissue culture, depending on the protocol used, can induce genomic instability resulting in large-scale changes likely to compromise final plant phenotype.

Dysregulation of the cohesin subunit RAD21 by Hepatitis C virus mediates host-virus interactions.

Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis, which often results in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCV possesses an RNA genome and its replication is confined to the cytoplasm. Yet, infection with HCV leads to global changes in gene expression, and chromosomal instability (CIN) in the host cell. The mechanisms by which the cytoplasmic virus affects these nuclear processes are elusive. Here, we show that HCV modulates the function of the Structural Maintenance of Chromosome (SMC) protein complex, cohesin, which tethers remote regions of chromatin. We demonstrate that infection of hepatoma cells with HCV leads to up regulation of the expression of the RAD21 cohesin subunit and changes cohesin residency on the chromatin. These changes regulate the expression of genes associated with virus-induced pathways. Furthermore, siRNA downregulation of viral-induced RAD21 reduces HCV infection. During mitosis, HCV infection induces hypercondensation of chromosomes and the appearance of multi-centrosomes. We provide evidence that the underlying mechanism involves the viral NS3/4 protease and the cohesin regulator, WAPL. Altogether, our results provide the first evidence that HCV induces changes in gene expression and chromosome structure of infected cells by modulating cohesin.

Cytogenetics and genetic introgression from wild relatives in soybean

Cultivated soybean, wild soybean, and 23 perennial Glycine species contain 2n = 40 chromosomes. Accessions of G. hirticaulis and G. tabacina have diploid (2n = 40) and tetraploid (2n = 80) chromosome numbers. In contrast, G. tomentella includes accessions with four cytotypes (2n = 38, 40, 78, or 80). Meiosis of G. max and G. soja F1 is normal and gene exchange is easy. Occasionally, accessions of the two species differ by chromosome structural changes (reciprocal translocation/paracentric inversion). The segregating populations inherit undesirable traits such as vining, lodging susceptibility, lack of complete leaf abscission, seed shattering, and small black coated seeds because of genetic drag. The introgression of useful genes from 26 wild perennial Glycine species to soybean has been restricted because of crossability barriers and requires extensive hybridization, immature seed rescue, and cytogenetic manipulations. This review paper discusses cytogenetics, gene pools of the soybean and the production of fertile G. max plants using 78-chromosome G. tomentella (PI 441001) as a paternal and maternal parent in crosses with G. max cv. ‘Dwight’ (2n = 40). Thus, reporting breaking of the intersubgeneric crossability barriers for the first time.

Molecular Cytogenetics of Pisum sativum L. Grown under Spaceflight-Related Stress.

The ontogenesis and reproduction of plants cultivated aboard a spacecraft occur inside the unique closed ecological system wherein plants are subjected to serious abiotic stresses. For the first time, a comparative molecular cytogenetic analysis of Pisum sativum L. (Fabaceae) grown on board the RS ISS during the Expedition-14 and Expedition-16 and also plants of their succeeding (F1 and F2) generations cultivated on Earth was performed in order to reveal possible structural chromosome changes in the pea genome. The karyotypes of these plants were studied by multicolour fluorescence in situ hybridization (FISH) with five different repeated DNA sequences (45S rDNA, 5S rDNA, PisTR-B/1, microsatellite motifs (AG)12, and (GAA)9) as probes. A chromosome aberration was revealed in one F1 plant. Significant changes in distribution of the examined repeated DNAs in karyotypes of the “space grown” pea plants as well as in F1 and F2 plants cultivated on Earth were not observed if compared with control plants. Additional oligo-(GAA)9 sites were detected on chromosomes 6 and 7 in karyotypes of F1 and F2 plants. The detected changes might be related to intraspecific genomic polymorphism or plant cell adaptive responses to spaceflight-related stress factors. Our findings suggest that, despite gradual total trace contamination of the atmosphere on board the ISS associated with the extension of the space station operating life, exposure to the space environment did not induce serious chromosome reorganizations in genomes of the “space grown” pea plants and generations of these plants cultivated on Earth.

Accurate Prediction of RH Genotypes Using Whole Genome Sequencing Data

IntroductionRBC alloimmunization is common in patients with sickle cell disease (SCD). Despite serological matching RBCs for major Rh antigens, Rh alloimmunization remains problematic. The Rh blood group is encoded by two genes RHD and RHCE, which exhibit extensive nucleotide polymorphism and chromosome structural changes, resulting in the formation of Rh variant antigens. Rh variants can result in loss of protein epitopes or expression of neo-epitopes, and are common in SCD patients. Hence SCD patients harboring Rh variants can be predisposed to Rh alloimmunization. Given the limitation of traditional serologic antigen typing for detection of Rh variants, molecular genotyping has become required. A DNA microarray-based platform, BioArray RHCE and RHD BeadChip (Immuncor) is available for RH genotyping. However, it detects the most common, but not all, variants. Whole exome sequence data have been used for prediction of Rh variants (Chou, et. al, Blood Adv., 2017), offer some advantages, including detection of rare variants, structural rearrangements and copy number variation. However, whole genome sequence (WGS) analysis of RHD/RHCE is challenging due to difficulties in mapping next generation sequencing (NGS) reads to this duplicated gene family. We developed a computational algorithm to identify RH variants using WGS data.MethodsThe pipeline included three major components, RH allele database construction, RH variant calling, and classification of Rh blood group according the identified variants. The RH allele database was built based on NCBI Blood Group Antigen Gene Mutation (BGMUT) and International Society of Blood Transfusion (ISBT) database. Since the alleles in the BGMUT and ISBT databases were specified according to conventional RH genes (RHD, L08429; RHCE, DQ322275) that are different from those on reference human genome, we first called the variations based on the reference human genome. The positions of the identified variations were subsequently corrected to match with the BGMUT and ISBT annotation system. Next, the NGS reads with low base quality and/or mapping quality were discarded during the variation calling step. Synonymous and non-synonymous amino acid changes were characterized for each polymorphism. Haplotypes were constructed for the segments with NGS read support. Gene sequencing coverage was calculated to determine gene deletions or amplifications. Lastly, we implemented an algorithm to predict RH genotypes based on a selection of candidate alleles by read-mapping profile which considers both sequence variations and sequence consistency followed by a likelihood-based ranking of all pairwise combinations of the selected alleles. The allele combination with the highest likelihood is considered the most likely pair of alleles at a given locus. Patient specimens used in this study were from participants of the Sickle Cell Clinical Research and Intervention Program (SCCRIP, Hankins et al. Pediatr Blood Cancer. 2018).ResultsWe validated our method in a cohort of 58 SCD patients whose RH genotypes had been determined by BioArray RhCE and RhD BeadChip and supplementary molecular tests that identify the most common variants among individuals of African descent. In this validation cohort including a total of 11 RHD and 13 RHCE alleles, our approach achieved a concordance rate of 85.85% (91 of 106 alleles) for RHD and 83.02% (88 of 106 alleles) for RHCE genotyping. WGS was highly sensitive in distinguishing homozygosity from heterozygosity of genes. By comparing the numbers of NGS reads on RH regions and whole genome average coverage, heterozygous deletion can be determined. Since WGS provides comprehensive genotyping, our analysis identified single nucleotide polymorphisms that were not identified by the BeadChip and supplemental molecular testing. The final source of discordance was likely due to the short read length of NGS such that haplotype phases cannot be correctly predicted if the variations are separated by thousands of base pairs, for which long read DNA sequencing or RNA/cDNA sequencing are required. Evaluation of the identified discrepancies is ongoing.ConclusionsWe developed and validated a diagnostic method for RH genotyping that leveraged the accuracy and flexibility of RH genotyping based on WGS data. With further optimization of our method, this may be useful for RBC genotype matching sickle cell patients to blood donors in the future. DisclosuresHankins:Novartis: Research Funding; Global Blood Therapeutics: Research Funding; NCQA: Consultancy; bluebird bio: Consultancy.

Mechanisms shaping the mutational landscape of the FRA3B/FHIT‐deficient cancer genome

Genome instability is an enabling characteristic of cancer that facilitates the acquisition of oncogenic mutations that drive tumorigenesis. Underlying much of the instability in cancer is DNA replication stress, which causes both chromosome structural changes and single base-pair mutations. Common fragile sites are some of the earliest and most frequently altered loci in tumors. Notably, the fragile locus, FRA3B, lies within the fragile histidine triad (FHIT) gene, and consequently deletions within FHIT are common in cancer. We review the evidence in support of FHIT as a DNA caretaker and discuss the mechanism by which FHIT promotes genome stability. FHIT increases thymidine kinase 1 (TK1) translation to balance the deoxyribonucleotide triphosphates (dNTPs) for efficient DNA replication. Consequently, FHIT-loss causes replication stress, DNA breaks, aneuploidy, copy-number changes (CNCs), small insertions and deletions, and point mutations. Moreover, FHIT-loss-induced replication stress and DNA breaks cooperate with APOBEC3B overexpression to catalyze DNA hypermutation in cancer, as APOBEC family enzymes prefer single-stranded DNA (ssDNA) as substrates and ssDNA is enriched at sites of both replication stress and DNA breaks. Consistent with the frequent loss of FHIT across a broad spectrum of cancer types, FHIT-deficiency is highly associated with the ubiquitous, clock-like mutation signature 5 occurring in all cancer types thus far examined. The ongoing destabilization of the genome caused by FHIT loss underlies recurrent inactivation of tumor suppressors and activation of oncogenes. Considering that more than 50% of cancers are FHIT-deficient, we propose that FRA3B/FHIT fragility shapes the mutational landscape of cancer genomes.

Karyomorphological studies from mitotic metaphases in three carp species

Karyological analysis of three carp species viz. Ctenopharyngodon idella, Hypophthalmichthyes molitrix, and Cyprinus carpio communis belonging to family Cyprinidae was carried out. The study samples of these species were collected from local fish farm in Haryana. The diploid chromosome number in C. idella was found to be 2n = 48, with 13 pairs of metacentric, 3 pairs of submetacentric and 8 pairs of acrocentric chromosomes. Chromosomal studies on the H. molitrix revealed the diploid chromosome number to be 2n = 48, with 6 pairs of metacentric, 6 pairs of submetacentric and 12 pairs of acrocentric chromosomes. The diploid chromosome number in C. c. communis was found to be 2n = 100, with 17 pairs of metacentric, 3 pairs of submetacentric, 1 pair of subtelocentric and 29 pairs of acrocentric chromosomes. Arm ratio, centromeric index and fundamental number of arms was also determined. The study reveals that diversification in these carp species of cyprinidae family is related to structural changes in chromosomes. Habitat conditions and anthropogenic activities might be responsible for incidence of pericentric inversions causing karyomorphological changes and thereby variation in karytype formulae vis-a-vis earlier reports.

Chromosomal Instability Induces Cellular Invasion in Epithelial Tissues

Most sporadic carcinomas with high metastatic activity show an increased rate of changes in chromosome structure and number, known as chromosomal instability (CIN). However, the role of CIN in driving invasiveness remains unclear. Using an epithelial model in Drosophila, we present evidence that CIN promotes a rapid and general invasive behavior. Cells with an abnormal number of chromosomes delaminate from the epithelium, extend actin-based cellular protrusions, form membrane blebs, and invade neighboring tissues. This behavior is governed by the activation of non-muscle Myosin II by Rho kinase and by the expression of the secreted EGF/Spitz ligand. We unravel fundamental roles of the mitogen-activated protein kinase pathways mediated by the Fos proto-oncogene and the Capicua tumor suppressor gene in the invasive behavior of CIN-induced aneuploid cells. Our results support the proposal that the simple production of unbalanced karyotypes contributes to CIN-induced metastatic progression.

Genetic variation of acquired structural chromosomal aberrations

Human malignancies are often hallmarked with genomic instability, which itself is also considered a causative event in malignant transformation. Genomic instability may manifest itself as genetic changes in the nucleotide sequence of DNA, or as structural or numerical changes of chromosomes. Unrepaired or insufficiently repaired DNA double-strand breaks, as well as telomere shortening, are important contributors in the formation of structural chromosomal aberrations (CAs). In the present review, we discuss potential mechanisms behind the formation of CAs and their relation to cancer. Based on our own studies, we also illustrate how inherited genetic variation may modify the frequency and types of CAs occurring in humans. Recently, we published a series of studies on variations in genes relevant to maintaining genomic integrity, such as those encoding xenobiotic-metabolising enzymes, DNA repair, the tumour suppressor TP53, the spindle assembly checkpoint, and cyclin D1 (CCND1). While individually genetic variation in these genes exerted small modulating effects, in interactions they were associated with CA frequencies in peripheral blood lymphocytes of healthy volunteers. Moreover, we observed opposite associations between the CCND1 splice site polymorphism rs9344 G870A and the frequency of CAs compared to their association with translocation t(11,14). We discuss the functional consequences of the CCND1 gene in interplay with DNA damage response and DNA repair during malignant transformation.Our review summarizes existing evidence that gene variations in relevant cellular pathways modulate the frequency of CAs, predominantly in a complex interaction. More functional/mechanistic studies elucidating these observations are required. Several questions emerge, such as the role of CAs in malignancies with respect to a particular phenotype and heterogeneity, the formation of CAs during the process of malignant transformation, and the formation of CAs in individual types of lymphocytes in relation to the immune response.

Genome dynamics over evolutionary time: “C-value enigma” in light of chromosome structure

Eukaryotic genome evolution integrates processes behind (i) chromosome plasticity (change in chromosome structure and number), (ii) genome stability maintenance (perfect stability would prevent adaptive processes) and (iii) genome size. Relationships between these variables remain enigmatic, hence the term “C-value enigma”. This term reflects an apparent lack of correlation between genome size and perceived organismal complexity, replacing an older term “C-value paradox”. A useful concept for explaining the enigma is the nucleotypic function, a pluralistic approach unifying a range of phenomena not covered by the conventional genotype and phenotype concepts. In this paper I expand the nucleotype function by adding two additional elements. First element is the “informatics metaphor” according to which genomes act as information-processing entities integrating “hardware” (structural DNA + epigentetic-related DNA) and “software” (protein-coding DNA) components of the genome into a single unit behind organismal fitness. Second element is gross chromosome restructuring, or chromothripsis, as a novel process behind evolutionary chromosome plasticity.

Cytogenetic study on some common bone tumours

This study aimed to detect the consistent chromosomal abnormalities of each type of common bone tumours . Thirty bone tumors specimens were processed for direct cytogenetic preparation , only (9 cases) showed success results for chromosomal preparation by banding technique , the results of cytogenetic study were 1- Osteosarcoma (4) cases revealed multiple numerical and structural changes with complex karyotype and pronounced cell to cell variation . chromosome 17 was the most frequent involved in these chromosomal alteration . Also loss or structural changes of chromosome 13 was found in (2) cases of osteosarcoma loss or gain of sex chromosome were detected in these cases , loss of Y chromosome in (2) cases ; loss of X chrosome in (1) case and gain of X chrosome in another case . 2- Osteochnodroma : reveled the simple numerical change with no structural change in one case . 3- Chondroblastoma : in this tumor structural and numerical abnormalities of chrosome 5 . 4- Chondrosarcoma : showed chromosomal aberration with multiple numerical and structural changes in chromosome (1) was of interest and monsomy 18 was reported in one case . 5- Giant cell tumors : It showed a complex changes and the range of chromosomal number was 50 – 58 with the characteristic telomeric fusion in malignant cases while simple numerical change only in benign giant cell tumor . Conclusion Cytogenetic study of both benign and malignant bone tumors have revealed abnormlities in the number and / or structures of chromosomes X, Y , 1,5,6,11 , 13,17,18 and complex chromosomal changes in malignant types of bone tumors .

Application of cytogenetic markers in the taxonomy of flat rock scorpions (Scorpiones: Hormuridae), with the description of Hadogenes weygoldti sp. n.

In the present study, we performed the first comparative cytogenetic study in Hadogenes species using both standard and molecular cytogenetic approaches. Information about the diploid set, number and distribution of 18S rDNA and telomeric sequences was obtained from three South African species, Hadogenes trichiurus (Gervais, 1843), H. zuluanus Lawrence, 1937 and H. weygoldti sp. n.. All species analysed differ considerably in the number of chromosomes (H. trichiurus 2n=48, H. zuluanus 2n=80, H. weygoldti sp. n. 2n=113). In contrast, the number of 18S rDNA clusters and distribution of telomeric sequences represent rather stable cytogenetic characters in Hadogenes. Within all karyotypes, we identified one pair of 18S rDNA clusters. The telomeric signals were exclusively on the terminal chromosomal regions. Interestingly, the chromosomal location of 18S rDNA clusters varied from terminal to interstitial in species karyotypes, indicating the presence of hidden structural chromosomal changes. Additionally, the present comparative study is complemented by the description of a new species, H. weygoldti sp. n., based on specific karyotype features and morphological characters. Finally, our cytogenetic results are compared with known chromosomal data of other Hadogenes species, and the use of cytogenetic approaches in the taxonomy of scorpions is discussed.