Ring Chromosome Research Articles

Effect of Black Cumin (Nigella sativa) Extracts in Inhibiting of the Mutagenic Activity of Mitomycin C in Albino Mice

The aim of this study is to investigate the ability of black cumin (Nigella sativa) aqueous extracts in reducing the genotoxic effects induced by mitomycin C (MMC) in male mice Mus musculus (balb/c strain). Nigella sativa (N. sativa) has been widely used as a medicinal plant that treats different diseases. To determine the genotoxic effects of mitomycin C, the mitotic index of somatic and germ cells and chromosomal aberrations (chromatid breaks, chromosome breaks, and ring chromosomes) were tested. Twenty-five animals were divided into three main groups: group one was used as a negative control treated with buffer saline, group two was used as a positive control treated orally with mitomycin C (2 mg/kg b. w.) for two days; group three, which was divided into three sub groups, was treated orally with three different doses of N. sativa extracts (50, 100, 150 mg/kg b. w.) for one week, and then treated with mitomycin C for two days. The results of this study showed a protective role of N. sativa effecting a significant increase (P<0.05) of the frequency of mitotic index of both somatic and germ cells. Additionally, N. sativa may improve therapeutic efficiency of mitomycin C by inhibiting the chromosomal aberrations.

Investigation of Chromosomal Abnormalities and Microdeletion/ Microduplication(s) in Fifty Iranian Patients with Multiple Congenital Anomalies.

Major birth defects are inborn structural or functional anomalies with long-term disability and adverse impacts on individuals, families, health-care systems, and societies. Approximately 20% of birth defects are due to chromosomal and genetic conditions. Inspired by the fact that neonatal deaths are caused by birth defects in about 20 and 10% of cases in Iran and worldwide respectively, we conducted the present study to unravel the role of chromosome abnormalities, including microdeletion/microduplication(s), in multiple congenital abnormalities in a number of Iranian patients. In this descriptive cross-sectional study, 50 sporadic patients with Multiple Congenital Anomalies (MCA) were selected. The techniques employed included conventional karyotyping, fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and array comparative genomic hybridisation (array-CGH), according to the clinical diagnosis for each patient. Chromosomal abnormalities and microdeletion/microduplication(s) were observed in eight out of fifty patients (16%). The abnormalities proved to result from the imbalances in chromosomes 1, 3, 12, and 18 in four of the patients. However, the other four patients were diagnosed to suffer from the known microdeletions of 22q11.21, 16p13.3, 5q35.3, and 7q11.23. In the present study, we report a patient with 46,XY, der(18)[12]/46,XY, der(18), +mar[8] dn presented with MCA associated with hypogammaglobulinemia. Given the patient's seemingly rare and highly complex chromosomal abnormality and the lack of any concise mechanism presented in the literature to justify the case, we hereby propose a novel mechanism for the formation of both derivative and ring chromosome 18. In addition, we introduce a new 12q abnormality and a novel association of an Xp22.33 duplication with 1q43q44 deletion syndrome. The phenotype analysis of the patients with chromosome abnormality would be beneficial for further phenotype-genotype correlation studies.

Biological Dosimetry Network in Africa: Establishment of a Dose-Response Curve Using Telomere and Centromere Staining.

Biological dosimetry, based on the relationship between the absorbed dose after exposure to ionizing radiation and the frequency of scored aberrations, has been and continues to be an important tool for estimating the dose after exposure. Dicentric chromosomes are considered to be the most specific and sensitive aberration related to radiation exposure. Here, we established the dose-response curve following in vitro irradiation of circulating lymphocytes from healthy donors from three African countries after scoring unstable chromosomal aberrations. Blood samples from 16 African donors were exposed to various doses (0 to 4 Gy) using an X-RAD320 x-ray system with a maximum photon energy of 250 kV at a dose rate of 0.1 Gy min. Blood lymphocytes were cultured for 48 h, and chromosomal aberrations were scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined. No dicentric chromosomes were found after the analysis of 2,669 first-division metaphases before in vitro exposure. We established a linear-quadratic dose-response curve based on the frequency of dicentric and ring chromosomes and calculated double-strand breaks, taking into account all scored aberrations. The generation of a specific dose-response curve for African donors will allow the practice of precise biological dosimetry in these countries. This work is the first step towards realizing an African biodosimetry network and the establishment of a biological dosimetry laboratory, which could play a major role in the application of radioprotection norms.

Comparative study of micronucleus assays and dicentric plus ring chromosomes for dose assessment in particular cases of partial-body exposure

Purpose: The goal was to compare the micronucleus (MN) and dicentric plus ring chromosomes (D + R) assays for dose assessment in cases of partial body irradiations (PBI).Materials and methods: We constructed calibration curves for each assay at doses ranging from 0 to 5 Gy of X-rays at dose rate of 0.275 Gy/min. To simulate partial-body exposures, blood samples from two donors were irradiated with 0.5, 1, 2 and 4 Gy and the ratios of irradiated to unirradiated blood were 25, 50, and 100%. Different tests were used to confirm if all samples were overdispersed or zero-inflated and for partial-body dose assessment we used the Qdr, Dolphin and Bayesian model.Results: In our samples for D + R calibration curve, practically all doses agreed with Poisson assumption, but MN exhibited overdispersed and zero-inflated cellular distributions. The exact Poisson tests and zero-inflated tests demonstrate that virtually all samples of D + R from PBI simulation fit the Poisson distribution and were not zero-inflated, but the MN samples were also overdispersed and zero-inflated. In the partial-body estimation, when Qdr and Dolphin methods were used the D + R results were better than MN, but the doses estimation defined by the Bayesian methodology were more accurate than the classical methods.Conclusions: Dicentric chromosomes continue to prove to be the best biological marker for dose assessment. However exposure scenarios of partial-body estimation, overdispersion and zero-inflation may not occur, it being a critical point not only for dose assessment, but also to confirm partial-body exposure. MN could be used as alternative assay for partial-body dose estimation, but in case of an accident without any information, the MN assay could not define whether the accident was a whole-body irradiation (WBI) or a PBI.

X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood.

Objective Turner Syndrome is associated with several phenotypic conditions associated with a higher risk of subsequent comorbidity. We aimed to evaluate the prevalence of congenital malformations and the occurrence of age-related comorbid conditions and to determine whether the frequencies of congenital and acquired conditions depend on X chromosome gene dosage, as a function of karyotype subgroup. Design and methods This national retrospective observational cohort study includes 1501 patients. We evaluated the prevalence of congenital malformations and the cumulative incidence of subsequent specific comorbidities at five-year intervals, from the ages of 10 to 30 years, with stratification by karyotype subgroup: 45,X (n = 549), 45,X/46,isoXq (n = 280), 46,X,r(X)/46,XX (n = 106), 45,X/46,XX (n = 221), presence of Y (n = 87). Results Median age was 9.4 (3.7-13.7) years at first evaluation and 16.8 (11.2-21.4) years at last evaluation. Congenital heart (18.9%) malformations were more frequent in 45,X patients, and congenital renal (17.2%) malformations were more frequent in 45,X, 45,X/46,isoXq and 46,X,r(X)/46,XX patients than in those with 45,X/46,XX mosaicism or a Y chromosome (P < 0.0001). The cumulative incidence of subsequent acquired conditions, such as thyroid disease, hearing loss, overweight/obesity, dyslipidemia and, to a lesser extent, celiac disease, glucose intolerance/type 2 diabetes, hypertension and liver dysfunction increased with age, but less markedly for patients with mosaicism than for those with other karyotypes. Patients with a ring chromosome were more prone to metabolic disorders. Conclusion These data suggest that X gene chromosome dosage, particularly for Xp genes, contributes to the risk of developing comorbidities.

Cytogenetic Analyses Revealed Different Genome Rearrangement Footprints in Four ×BrassicoraphanusLines with Different Fertility Rates

×Brassicoraphanus (AARR, 2n = 38) is a synthetic intergeneric allopolyploid between Brassica rapa L. ssp. pekinensis (AA, 2n = 20) and Raphanus sativus L. var. rafiphera (RR, 2n = 18). Abnormalities in meiosis are main causes for infertility, especially in recent intergeneric allopolyploids. Several ×Brassicoraphanus lines showing varied fertility rates were produced previously, but no cytogenetic data specifying the reasons for infertility have been reported. In this study, we performed cytogenetic analyses in BB4, BB6, BB12, and BB50 lines to evaluate their chromosomal composition and behavior during meiosis. The four lines had relatively small chromosomes, ranging in length from 1.82 to 5.72 μm. BB6, BB12, and BB50 have euploid chromosome number of 2n = 38, whereas BB4 is an aneuploid with 2n - 1 = 37. Fluorescent in situ hybridization karyotype analysis by using 5S/45S rDNA revealed 5/7, 6/7, 5/5 and 5/5 pairs in BB4, BB6, BB12 and BB50, respectively. Genomic in situ hybridization analysis on cells in prophase I revealed varying frequencies of tetravalent pairing and sticky, ring, rod, and laggard chromosomes across the lines, which were more abundant in BB4 and BB6. Unlike BB4 and BB6, both BB12 and BB50 are known to have relatively higher seed fertility and uniform plant morphology. The varied degrees of chromosomal pairing stability during meiosis could explain the different fertility rates among the four ×Brassicoraphanus lines in this study. These data might facilitate breeding programs of ×Brassicoraphanus and further cytogenomic analyses.

Gene Deletions due to Ring Chromosome 16 are Associated with Low Reproductive Potential, a Novel Observation

Diminished ovarian reserve (DOR) is characterized by decreased number of oocytes associated with poor ovarian response (POR) to controlled ovarian hyperstimulation (COH). Presently, few specific known chromosomal abnormalities are associated with DOR. Ring chromosome is among the least likely genetic abnormality reported to impact female infertility. It may occurs when two breaks are created in one chromosome and the resulting ends fuse to form a ring, leading to loss of distal genetic material.

A case report of ring chromosome 18 with tetralogy of fallot

Background: Ring Chromosome 18 is a rare chromosomal disorder with loss of geneticmaterial from one or both ends of the 18th chromosome and fusion of the chromosomalends to form a ring. Associated symptoms and physical features may beextremely variable.Case report: we observed a 2.5 year old girl with the features typical for r(18)carriers additionally manifested a Tetralogy of fallot. Chromosomal analysis on thebasis of G-banding technique was performed. Chromosomal investigation appeared as46, XY,r(18) (p11.31q22.3).Conclusion: This information may help healthcare team make diagnosis a personwith ring 18.

Abstract P1-07-01: Novel role of the tumor suppressor ductal epithelium associated ring chromosome 1 (DEAR1) in regulation of breast stem/progenitor cell properties

Abstract Introduction: Breast cancer is the most commonly diagnosed cancer and third-leading cause of cancer-related deaths in women in America. A quarter of lesions diagnosed annually are ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC). Without therapeutic intervention, 30-50% of DCIS cases can progress to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify DCIS patients at higher risk of progression or recurrence. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS lesions. DEAR1 regulates acinar morphogenesis and cell polarity, and is a negative regulator of TGF-beta-driven EMT by binding to and ubiquitinating SMAD3, thereby limiting the amount of SMAD3 available to activate an EMT signature. Overexpression of EMT master regulators, or exposure to TGF-beta in immortalized human mammary epithelial cells (HMECs), results in mammosphere formation and breast stem cell markers, thus linking the EMT process to acquisition of stem cell characteristics. Methods: Stable lentiviral shRNA knockdown, in vitro mammosphere assay, cytospin, immunofluorescence, immunoprecipitation, western blot analysis, ubiquitination and real-time quantitative PCR were performed. Results: DEAR1 knockdown in immortal HMECs resulted in a significant enhancement of primary mammosphere formation and growth compared to controls, suggesting that DEAR1 may regulate stem/progenitor cell properties; this effect was greater when cells were exposed to TGF-beta. To determine if DEAR1 regulates stem cell properties through regulation of SMAD3 levels, DEAR1-SMAD3 double knockdown clones were examined for mammosphere formation. Results indicated fewer mammospheres in double knockdown clones, but only in the presence of TGF-beta, suggesting that the mammosphere phenotype is partially dependent on the TGF-beta-SMAD3 pathway. The observation that loss of DEAR1 alone results in a stem/progenitor cell phenotype indicates that DEAR1 may regulate mammosphere formation independent of its role in regulating the TGF-beta pathway. HMEC mammospheres express higher levels of stem cell marker aldehyde dehydrogenase (ALDH1) and co-express luminal and basal cytokeratins, suggesting bipotential capacity. We also observed upregulation of SNAI2 and ZEB1, master EMT and stem cell regulators, in DEAR1 knockdown HMECs. DEAR1 interacted with SNAI2 by co-immunoprecipitation analysis and also promoted the polyubiquitination of SNAI2. Conclusions: Loss of the tumor suppressor/polarity regulator DEAR1 promotes stem cell properties in part through the DEAR1-TGF-beta-SMAD3 axis. We demonstrate a DEAR1-SNAI2 axis that may partially regulate stem/progenitor cell properties in HMECs through the polyubiquitination of SNAI2, a master regulator of EMT and stemness. These mechanisms governing acquisition of the stem cell properties may contribute to understanding how DCIS progress to IDC. Citation Format: Le U, Chen N, Balasenthil S, Killary AM. Novel role of the tumor suppressor ductal epithelium associated ring chromosome 1 (DEAR1) in regulation of breast stem/progenitor cell properties [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-07-01.

Dose response of prematurely condensed chromosome rings after gamma irradiation

Purpose: This paper presents a calibration curve for prematurely condensed chromosome rings (PCC-ring) which are scarce in cytogenetic dosimetry; here we analyzed the behavior of the PCC-ring frequency and PCC index after gamma irradiation in the dose interval from 0 to 20 Gy.Materials and methods: PCC-rings were induced in lymphocytes with Calyculin A. A total of 5788 PCC cells in G1, G2/M, and M/A stages were analyzed.Results: The best fitting curve between the frequency of PCC ring (Y) and the Dose (D) was obtained with the equation Y = (0.0308 ± 0.0012) D. The distribution of rings by cell followed a Poisson distribution. The PCC index was correlated with radiation dose and decreased in a dose-dependent manner.Conclusion: This PCC-ring dose–effect curve can be used in case of high dose accidental overexposure to gamma radiation, allowing a dose assessment in a reliable way in most of the simulated irradiation analyzed.

Utility and performance of bacterial artificial chromosomes-on-beads assays in chromosome analysis of clinical prenatal samples, products of conception and blood samples.

Chromosome analysis of prenatal samples and products of conception (POC) has conventionally been done by karyotyping (KT). Shortcomings of KT like high turnaround time and culture failure led to technology innovations, such as the bacterial artificial chromosomes (BAC)s-on-Beads (BoBs)-based tests, Prenatal BoBs (prenatal samples) and KaryoLite BoBs (POC samples). In the present study, we validated and evaluated the utility of each test on prenatal, POC and blood samples. Study A (n = 305; 259 prenatal + 46 blood/POC) and Study B (n = 176; 146 POC/chorionic vill + 30 blood/amniotic fluid) samples were analyzed using Prenatal and KaryoLite BoBs kits, respectively. KT, array-based Comparative Genomic Hybridization (arrayCGH) and fluorescence in situ hybridization (FISH) were used for comparison of results. Ability of KaryoLite BoBs to identify ring chromosomes was tested. Prenatal BoBs had zero test failure rate and results of all samples were concordant with KT results. Totally four microdeletions were identified by Prenatal BoBs but not by KT. In Study B, all but two POC samples (one triploid and one tetraploid) were concordant with KT and arrayCGH. Partial chromosomal imbalance detection rate was ~64% and KaryoLite BoBs indicated the presence of a ring chromosome in all four cases. The failure rate of KaryoLite BoBs was 3%. We conclude that Prenatal BoBs (common aneuploidies and nine microdeletions) together with KT constitutes more comprehensive prenatal testing compared to FISH and KT. KaryoLite BoBs for aneuploidies of all chromosomes is highly successful in POC analysis and the ability to indicate presence of ring chromosomes improves its clinical sensitivity. Both tests are robust and could also be used for different specimens.

MLPA is a practical and complementary alternative to CMA for diagnostic testing in patients with autism spectrum disorders and identifying new candidate CNVs associated with autism.

BackgroundAutism spectrum disorder (ASD) is a complex heterogeneous developmental disease with a significant genetic background that is frequently caused by rare copy number variants (CNVs). Microarray-based whole-genome approaches for CNV detection are widely accepted. However, the clinical significance of most CNV is poorly understood, so results obtained using such methods are sometimes ambiguous. We therefore evaluated a targeted approach based on multiplex ligation-dependent probe amplification (MLPA) using selected probemixes to detect clinically relevant variants for diagnostic testing of ASD patients. We compare the reliability and efficiency of this test to those of chromosomal microarray analysis (CMA) and other tests available to our laboratory. In addition, we identify new candidate genes for ASD identified in a cohort of ASD-diagnosed patients.MethodWe describe the use of MLPA, CMA, and karyotyping to detect CNV in 92 ASD patients and evaluate their clinical significance.ResultPathogenic and likely pathogenic mutations were identified by CMA in eight (8.07% of the studied cohort) and 12 (13.04%) ASD patients, respectively, and in eight (8.07%) and four (4.35%) patients, respectively, by MLPA. The detected mutations include the 22q13.3 deletion, which was attributed to ring chromosome 22 formation based on karyotyping. CMA revealed a total of 91 rare CNV in 55 patients: eight pathogenic, 15 designated variants of unknown significance (VOUS)—likely pathogenic, 10 VOUS—uncertain, and 58 VOUS—likely benign or benign. MLPA revealed 18 CNV in 18 individuals: eight pathogenic, four designated as VOUS—likely pathogenic, and six designated as VOUS—likely benign/benign. Rare CNVs were detected in 17 (58.62%) out of 29 females and 38 (60.32%) out of 63 males in the cohort. Two genes, DOCK8 and PARK2, were found to be overlapped by CNV designated pathogenic, VOUS—likely pathogenic, or VOUS—uncertain in multiple patients. Moreover, the studied ASD cohort exhibited significant (p < 0.05) enrichment of duplications encompassing DOCK8.ConclusionMultiplex ligation-dependent probe amplification and CMA yielded concordant results for 12 patients bearing CNV designated pathogenic or VOUS—likely pathogenic. Unambiguous diagnoses were achieved for eight patients (corresponding to 8.7% of the total studied population) by both MLPA and CMA, for one (1.09%) patient by karyotyping, and for one (1.09%) patient by FRAXA testing. MLPA and CMA thus achieved identical reliability with respect to clinically relevant findings. As such, MLPA could be useful as a fast and inexpensive test in patients with syndromic autism. The detection rate of potentially pathogenic variants (VOUS—likely pathogenic) achieved by CMA was higher than that for MLPA (13.04% vs. 4.35%). However, there was no corresponding difference in the rate of unambiguous diagnoses of ASD patients. In addition, the results obtained suggest that DOCK8 may play a role in the etiology of ASD.

Cytogenetic effects of gestogens on women with threatened miscarriage in Duhok Province, Kurdistan Region, Iraq

Background: Gestogens have been recommended to have a place in the prevention of threatened miscarriage and spontaneous pregnancy loss during the first 3 months of pregnancy. Certain studies consider that this steroid hormone has genotoxic effect because they directly involved in the change of DNA structure. Objectives: This study aims to investigate the cytogenetic effects of gestogens on peripheral blood lymphocytes of pregnant women, by damaged cells and chromosomal aberrations, as well as evaluate the models for hormonal therapy in vivo. Materials and Methods: Blood sample from 30 women with threatened miscarriage, who received gestogen therapy in the first 3 months, Were taken. Cytogenetic analyses and karyotyping were performed for Each patient Before and after therapy. Results: The numerical chromosomal aberrations which found in blood lymphocytes of women before taking gestogens were 44,XX and 48,XX. The same result was observed after taking gestogens. The percentage levels of structural chromosomal aberrations were ring chromosome (2.06%), chromatid breaks (12.47%), chromatid gaps (1.65%), dicentric (0.55%), acentric chromosome (4.02%), and interchange chromosome (12.5%). Whereas, the abnormalities after treatment with gestogens were ring chromosome (5.31%), chromatid breaks (42.19%), chromatid gaps (20.86%), dicentric (7.50%), acentric chromosome (17.75%), and interchange chromosome (43.97%). Conclusion: Gestogens as hormonal substitute therapy do not induce numerical chromosomal aberrations but have a significant increase of structural chromosomal aberrations Gestogens have genotoxic effects on human lymphocyte chromosomes at wide range of concentrations. So the potential benefits and side effects of it must be weighed up against the deleterious effects.

Overview of liposarcomas and their genomic landscape

Liposarcoma (LPS) is among the most common soft tissue sarcoma affecting adults. LPS is divided into three biologic subtypes characterized by specific genetic alterations. The most common LPS subtypes, well-differentiated and dedifferentiated LPS, are nearly uniformly characterized by ring chromosomes and giant markers with chromosomal amplification of 12q13-15 and resulting amplification of oncogenes MDM2, CDK4, and HMGA2. Myxoid/round cell LPS commonly exhibits a distinctive (12; 16) translocation resulting in the FUS-DDIT3 fusion gene. Finally, pleomorphic LPS harbors diverse complex genomic changes and chromosomal rearrangements and frequent mutations in TP53, RB1, and NF1 leading to dysregulation of tumor suppressor pathways. In this review, we summarize the currently available knowledge on the genomics and genetics of LPS subtypes as well as recent advances in the multimodality management of LPS.

Human Lymphocyte Metaphase Chromosome Preparation for Radiation-Induced Chromosome Aberration Analysis.

Radiation-induced chromosomal aberration analysis for metaphase chromosomes is well established and the golden standard for human biodosimetry. This method can estimate doses of human radiation exposure after nuclear accident and unwanted radiation exposure from their lymphocytes. The natural background frequency of dicentric chromosome for human lymphocytes is less than 1% and any increase in dicentric and centric ring chromosomes may be highly associated with radiation exposure. With the appropriate number of metaphase cells, one can detect the exposure of more than 0.1Gy by observing dicentric and centric ring chromosomes. Dicentric chromosome analysis is relying on morphological changes and may be difficult for researchers without appropriate training. This method is time consuming and labor intensive, but still currently the most reliable technique and analysis needs only light microscopes with high magnification objectives and trained personnel. Recent research enables us to visualize dicentric chromosomes clearly with fluorescent markers for easy detection of dicentric and centric ring chromosomes. This chapter will introduce classical dicentric analysis of human lymphocyte cells with Giemsa staining.

Coexistence of Autism and Ring Chromosome 22

Coexistence of Autism and Ring Chromosome 22

Differential Incremental Equilibrium Geometry - Spatial Folding of Protein Particles, Genome Expression and Bidirectional Semiconservative Replication of Ring Chromosomes

The research direction of this paper is to study the interdisciplinary subjects of life science, mathematics and computer science at the molecular level from the life science Molecular Cell Biology. On the basis of mathematical primitive innovation Differential Incremental Balanced Geometry, the cell modification of normal chromosome mitosis was established at the molecular level, and the normal cell tissue spatial morphology with initial boundary was established. DNA is used to unravel double helix and separate double strands to solve the protein skeleton structure of bi-directional Semi-Reserved replication of cyclic chromosomes in life sciences at the molecular level. Therefore, it establishes and reveals the duplication fork and bidirectional duplication of molecular cell biology model, the internal structure and regularity of cyclic chromosomes bound by cyclic DNA double helix and many proteins. New mathematics is integrated into the micro-activities of cell modification in life sciences. The topological geometric image of the solitary wavelet with supersymmetric structure is constructed, which reflects the correct abstract model of cell modification and provides dynamic structure for DNA gene sequencing, etc. It also provides a mature mathematical basis for reliable predictability of gene editing.

PNA Telomere and Centromere FISH Staining for Accurate Analysis of Radiation-Induced Chromosomal Aberrations.

Dicentric and centric ring chromosomes are used for radiation-induced damage analysis and biodosimetry after radiation exposure. However, Giemsa stain-based cytogenetic analysis is labor-intense and time-consuming. Moreover, the disadvantage of Giemsa based chromosome analysis is a potential poor reproducibility when researchers are not fully trained for analysis. These problems come from analysis of morphological abnormality of chromosomal aberrations. Locus-specific FISH probes were used to overcome this problem. Centromere probes can visualize centromere locations and help identify dicentric chromosomes and centric rings. Telomere probes help to identify terminal deletion and telomere fusions. Probes were originally designed with a DNA probe but Peptide nucleic acid (PNA) probes took the place of DNA probes. This chapter introduces PNA telomere and centromere FISH staining and accurate analysis of chromosomal aberrations.

Investigation of Chromosomal Abnormalities and Microdeletion/ Microduplication(s) in Fifty Iranian Patients with Multiple Congenital Anomalies

Objective Major birth defects are inborn structural or functional anomalies with long-term disability and adverse impacts on individuals, families, health-care systems, and societies. Approximately 20% of birth defects are due to chromosomal and genetic conditions. Inspired by the fact that neonatal deaths are caused by birth defects in about 20 and 10% of cases in Iran and worldwide respectively, we conducted the present study to unravel the role of chromosome abnormalities, including microdeletion/microduplication(s), in multiple congenital abnormalities in a number of Iranian patients. Materials and Methods In this descriptive cross-sectional study, 50 sporadic patients with Multiple Congenital Anomalies (MCA) were selected. The techniques employed included conventional karyotyping, fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and array comparative genomic hybridisation (array-CGH), according to the clinical diagnosis for each patient. Results Chromosomal abnormalities and microdeletion/microduplication(s) were observed in eight out of fifty patients (16%). The abnormalities proved to result from the imbalances in chromosomes 1, 3, 12, and 18 in four of the patients. However, the other four patients were diagnosed to suffer from the known microdeletions of 22q11.21, 16p13.3, 5q35.3, and 7q11.23. ConclusionIn the present study, we report a patient with 46,XY, der(18)[12]/46,XY, der(18), +mar[8] dn presented with MCA associated with hypogammaglobulinemia. Given the patient’s seemingly rare and highly complex chromosomal abnormality and the lack of any concise mechanism presented in the literature to justify the case, we hereby propose a novel mechanism for the formation of both derivative and ring chromosome 18. In addition, we introduce a new 12q abnormality and a novel association of an Xp22.33 duplication with 1q43q44 deletion syndrome. The phenotype analysis of the patients with chromosome abnormality would be beneficial for further phenotype-genotype correlation studies.

Retraction: Suppression of HMGA2 Protein Synthesis Could Be a Tool for the Therapy of Well Differentiated Liposarcomas Overexpressing HMGA2.

Atypical lipomatous tumors (ALTs)/well-differentiated liposarcomas represent a distinctive subset of mesenchymal neoplasms featuring mature adipocytic proliferation. These tumors are characterized cytogenetically by the presence of supernumerary ring and/or long marker chromosomes that contain several copies of the chromosomal region 12q13-15, in which the HMGA2 gene is located. Deregulation of the HMGA2 gene is a common molecular alteration implicated in the development of a variety of benign tumors, such as lipomas, uterine leiomyomas, and pulmonary chondroid hamartomas. In this study, we observed HMGA2 overexpression in 7 of 12 ALT primary cell cultures examined. Subsequently, we generated an adenovirus containing the HMGA2 gene in the antisense orientation (Ad-A2as) to study the effect of HMGA2 protein suppression in ALT cells. The infection of six ALT cells, three of which were positive for HMGA2 expression, resulted in growth inhibition coupled with a significant increase in apoptosis. In addition, the growth of the ALT cells negative for HMGA2 expression was not affected by the infection with either the Ad-A2as or the control virus. On the basis of these findings, the targeting of the HMGA2 protein expression may represent a promising approach for treating the well-differentiated liposarcomas resistant to conventional therapies.