What Causes Down Syndrome?

Trisomy 21 (Down Syndrome) is the model human phenotype for all genome gain-dosage imbalance situations, including microduplications. Years after the sequencing of chromosome 21, the discovery of functional genomics and the creation of multiple cellular and mouse models provided an unprecedented opportunity to demonstrate the molecular consequences of genome dosage imbalance. It was stated years ago that Down syndrome, caused by meiotic separation of chromosome 21 in humans, is associated with advanced maternal age, but defining and understanding other risk factors is insufficient. Commonly referred to as Down syndrome (DS) in humans, trisomy 21 is the most cited genetic cause of mental retardation. In about 95% of cases, the extra chromosome occurs as a result of meiotic non- nondisjunction (NDJ) or abnormal separation of chromosomes. In most of these cases the error occurs during maternal oogenesis, especially in meiosis I

Germline Pathogenic Variants Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma

The aim of this study was to evaluate germline variant frequencies of pheochromocytoma and paraganglioma targeted susceptibility genes with next-generation sequencing method. Germline DNA from 75 cases were evaluated with targeted next-generation sequencing on an Illumina NextSeq550 instrument. KIF1B, RET, SDHB, SDHD, TMEM127, and VHL genes were included in the study, and Sanger sequencing was used for verifying the variants. The pathogenic/likely pathogenic variants were in the VHL, RET, SDHB, and SDHD genes, and the diagnosis rate was 24% in this study. Three different novel pathogenic variants were determined in five cases. This is the first study from Turkey, evaluating germline susceptibility genes of pheochromocytoma and paraganglioma with a detection rate of 24% and three novel variants. All patients with pheochromocytoma and paraganglioma need clinical genetic testing with expanded targeted gene panels for higher diagnosis rates

Mechanisms of Aneuploidy

Aneuploidy is a very common occurrence in humans and occurs in an estimated 20–40% of all pregnancies. It is the most prominent cause of miscarriages and congenital defects in humans and is the main obstacle to infertility treatment. The vast majority of aneuploidies are caused by maternal meiotic non-disjunction errors. High levels of recombination errors were observed in studies on fetal oocytes. This suggests that some oocytes are more prone to not being separated due to events occurring before birth. Cell cycle checkpoints that work in the meiotic phase and metaphase-anaphase transition work more moderately in women than in men. As a result, while there are abnormal cells that have been sorted out in spermatogenesis, in females these cells can escape the actual control and ultimately give rise to aneuploid eggs

The Effects of Salinity and Salinity plus Metal (Chromium and Lead) Exposure on ATPase Activity in the Gill and Intestine of Tilapia Oreochromis niloticus

WOS: 000314040800014PubMed ID: 23114534Freshwater organisms are highly sensitive to increases in salinity because they causes serious osmoregulation problems. Salinity of inland waters can be increased as a result of anthropogenic activities. In this study, freshwater fish Oreochromis niloticus were exposed individually to increased salinities (0, 2, and 8 ppt) alone and salinity+metal [1 mu g/mL chromium (Cr) or lead (Pb) exposure at 2 and 8 ppt] exposures for different time periods (1, 7, and 14 days) to investigate the response of Na+/K+-ATPase and Mg2+-ATPase in the osmoregulatory tissues (gill and intestine). Results showed that enzyme activity varied depending on salinity, tissue, metal, and exposure duration. Metal levels in controls and salinity-exposed groups were lower than the detection limit, although significant Cr and Pb accumulation occurred in the salinity+metal combination groups. In salinity-exposed groups, there were increasing trends in the enzyme activity, whereas there were decreasing trends in the metal+salinity groups. Gill ATPases were more affected by the exposure conditions compared with intestine ATPases. Results showed that salinity+metal exposure both played significant roles on ATPase activities in the osmoregulatory tissues, although the alterations in the activity were mostly insignificant supporting compensation mechanisms. Results also suggest that the osmoregulation of freshwater fish should be investigated in toxicity- monitoring programs in inland waters.Cukurova University (Turkey)Cukurova University [FEF 2010YL23]This study was supported by a grant (Grant No. FEF 2010YL23) to E. Baysoy from Cukurova University (Turkey)

Methylation of RARß is a new clinical biomarker for treatment in higher-grade gliomas

Background: The dysregulation of various pathways and cellular processes contributes to the carcinogenic transition from low-grade gliomas to high-grade gliomas. The altered tumor microenvironment, altered epigenetic state, and high mutation heterogeneity are critical factors in glial tumors. The morphogen retinoic acid (RA) controls the homeostasis, regeneration, and development of the brain. RA receptor (RAR) gene methylation has been shown in different types of glial tumors. Aims and Objectives: This study assessed the RARß gene as a potential therapeutic target in gliomas. Materials and Methods: Using in silico methods, potential drugs targeting the RARß gene were compared based on temozolomide's effectiveness in treating gliomas. Results and Conclusion: Computational techniques can be used to identify drug-mediated pathways. This in silico study holds promise for RARB and RARB-targeted treatment strategies in gliomas

RAR beta gene methylation is a candidate for primary glioblastoma treatment planning.

Background: We screened RAR beta methylation in primary glioblastoma multiforme (GBM) and the results were evaluated based on the clinical data and treatment type

IDH1 mutations is prognostic marker for primary glioblastoma multiforme but MGMT hypermethylation is not prognostic for primary glioblastoma multiforme

Purpose: To establish the frequency of IDH1 mutations and MGMT methylation in primary glioblastomas. Experimental design: We screened primary glioblastoma multiforme (GBM) in a population-based study for IDH1 mutations and MGMT methylation and correlated them with clinical data

RAR\u3b2 gene methylation is a candidate for primary glioblastoma treatment planning.

Background: We screened RAR\u3b2 methylation in primary glioblastoma multiforme (GBM) and the results were evaluated based on the clinical data and treatment type. Objective: The objective of this study was to find new areas for the usage of MS-HRM applications in the determination of methylation levels in primary GBM samples and it shows the association of RAR\u3b2 methylation with the clinical outcome. Methods: In our study, tumor samples were collected during surgical resection by the Department of Neurosurgery. The clinical and radiologic data was carefully reviewed, compared, and evaluated with the histological results. The methylation status of RAR\u3b2 was determined by using MS-HRM. Results: RAR\u3b2 gene methylation was detected in 24 out of 40 cases (60%), with different quantitative methylation levels. The mean survival time was 19 months form ethylated cases and 15 months for the non-methylated cases. The survival time of the patients who received treatment was 25 months and the survival time of the patients who received radiotherapy alone or where no treatment protocol applied was 15-20 months. Therefore, a significant difference in survival rates has been observed (P<0.05). This study indicates a potential prognostic value for GBM treatment planning. Conclusion: Our study is the first study to investigate RAR\u3b2 methylation in primary GBMs. We conclude that the RAR\u3b2 gene could be a new prognostic and predictive candidate marker to designate the treatment protocol for primary GBMs. Keywords