OBJECTIVE: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from enzyme deficiencies associated with steroidogenesis. The clinical presentation of non-classic CAH (NCAH) in females is often indistinguishable from other hyperandrogenic disorders like polycystic ovary syndrome (PCOS). The data on the prevalence of NCAH in unselected women in the literature is scanty. The research aimed to evaluate the prevalence of NCAH, carrier frequencies, and the correlation between clinical symptoms and genotype in Turkish women.
METHODS: The study group comprised two hundred and seventy randomly-selected unrelated asymptomatic women of reproductive age (18-45). Subjects were recruited from female blood donors. All volunteers underwent clinical examination and hormone measurements. The protein-encoding exons and exon-intron boundaries of the CYP21A2, CYP11B1, HSD3β2 and CYP21A2 promoter were sequenced by direct DNA sequencing.
RESULTS: After genotyping, seven (2.2%) individuals were diagnosed with NCAH. The heterozygous carrier frequencies of CYP21A2, CYP21A2 promoter, CYP11B1, and HSD3β2 genes with 34, 34, 41, and 1 pathologic mutation were determined at 12.6%, 12.6%, 15.2%, and 0.37% of volunteers, respectively. Gene-conversion (GC) frequencies between CYP21A2/CYP21A1P and CYP11B1/CYP11B2 were determined as 10.4% and 14.8%, respectively.
CONCLUSIONS: Despite GC-derived higher mutation frequency determined in the CYP11B1 gene, the reason for the low frequency of NCAH due to 11OHD compared to 21OHD might be that gene-conversion arises with active CYP11B2 rather than an inactive pseudogene. HSD3β1 exhibits high homology with HSD3β2 located on the same chromosome; remarkably, it demonstrates low heterozygosity and no GC, most probably the outcome of a tissue-specific expression pattern.

Genomic data analysis is a fundamental system for monitoring pathogen evolution and the outbreak of infectious diseases. Based on bioinformatics and deep learning, this study was designed to identify the genomic variability of SARS-CoV-2 worldwide and predict the impending mutation rate. Analysis of 259044 SARS-CoV-2 isolates identified 3334545 mutations with an average of 14.01 mutations per isolate. Globally, single nucleotide polymorphism (SNP) is the most prevalent mutational event. The prevalence of C > T (52.67%) was noticed as a major alteration across the world followed by the G > T (14.59%) and A > G (11.13%). Strains from India showed the highest number of mutations (48) followed by Scotland, USA, Netherlands, Norway, and France having up to 36 mutations. D416G, F106F, P314L, UTR:C241T, L93L, A222V, A199A, V30L, and A220V mutations were found as the most frequent mutations. D1118H, S194L, R262H, M809L, P314L, A8D, S220G, A890D, G1433C, T1456I, R233C, F263S, L111K, A54T, A74V, L183A, A316T, V212F, L46C, V48G, Q57H, W131R, G172V, Q185H, and Y206S missense mutations were found to largely decrease the structural stability of the corresponding proteins. Conversely, D3L, L5F, and S97I were found to largely increase the structural stability of the corresponding proteins. Multi-nucleotide mutations GGG > AAC, CC > TT, TG > CA, and AT > TA have come up in our analysis which are in the top 20 mutational cohort. Future mutation rate analysis predicts a 17%, 7%, and 3% increment of C > T, A > G, and A > T, respectively in the future. Conversely, 7%, 7%, and 6% decrement is estimated for T > C, G > A, and G > T mutations, respectively. T > G\\A, C > G\\A, and A > T\\C are not anticipated in the future. Since SARS-CoV-2 is mutating continuously, our findings will facilitate the tracking of mutations and help to map the progression of the COVID-19 intensity worldwide.

UNASSIGNED: Certain genetic mutations could have a role in the etiology of acute myeloid leukemia (AML). Hereby, in this study, we primarily aimed to investigate the distribution of genetic mutations in AML patients. We also attempted to analyze the incidence of genetic mutations in AML patients from Turkey.This retrospective study included a total of 126 patients diagnosed with AML, who had molecular mutation test results or records in their patient files. The patients who were not citizens of the Republic of Turkey were not included in the study.It was observed that analyses for at least 1 c-kit exon mutation had been carried out on 76 patients, which detected no c-kit mutation among the types of genetic mutations investigated in all of those 76 patients. We found the frequency of FMS-like tyrosine kinase 3-internal tandem duplication mutation as 25%. The prevalence of translocation(15;17) was approximately 11% and the prevalence of translocation(8;21) was % 6.25. In addition, we also showed that the frequency of inversion16 was nearly 3.7%.Lastly, the possibility of c-kit mutation in AML patients from Turkey might actually be low.

OBJECTIVE: The study of minimal ter operon as a determinant of tellurium resistance (TeR) is important for the purpose of confirming the relationship of these genes to the pathogenicity of microorganisms. The ter operon is widespread among bacterial species and pathogens, implicated also in phage inhibition, oxidative stress and colicin resistance. So far, there is no experimental evidence for the role of the Escherichia coli (E. coli) minimal ter operon in ultraviolet C (UVC) resistance, biofilm formation and auto-aggregation. To identify connection with UVC resistance of the minimal ter operon, matched pairs of Ter-positive and -negative E. coli cells were stressed and differences in survival and whole genome sequence analysis were performed. This study was aimed also to identify differences in phenotype of cells induced by environmental stress.
METHODS: In the current study, a minimal ter operon(terBCDEΔF) originating from the uropathogenic strain E. coli KL53 was used. Clonogenic assay was the method of choice to determine cell reproductive death after treatment with UVC irradiation at certain time intervals. Bacterial suspensions were irradiated with 254 nm UVC-light (germicidal lamp in biological safety cabinet) in vitro. UVC irradiance output was 2.5 mW/cm2 (calculated at the UVC device aperture) and plate-lamp distance of 60 cm. DNA damage analysis was performed using shotgun sequencing on Illumina MiSeq platform. Biofilm formation was measured by a crystal violet retention assay. Auto-aggregation assay was performed according to the Ghane, Babaeekhou & Ketabi (2020).
RESULTS: A large fraction of Ter-positive E. coli cells survived treatment with 120-s UVC light (300 mJ/cm2) compared to matched Ter-negative cells; ∼5-fold higher resistance of Ter-positive cells to UVC dose (p = 0.0007). Moreover, UVC surviving Ter-positive cells showed smaller mutation rate as Ter-negative cells. The study demonstrated that a 1200-s exposure to UVC (3,000 mJ/cm2) was sufficient for 100% inhibition of growth for all the Ter-positive and -negative E. coli cells. The Ter-positive strain exhibited of 26% higher auto-aggregation activities and was able to inhibit biofilm formation over than Ter- negative strain (**** P < 0.0001).
CONCLUSIONS: Our study shows that Ter-positive cells display lower sensitivity to UVC radiation, corresponding to a presence in minimal ter operon. In addition, our study suggests that also auto-aggregation ability is related to minimal ter operon. The role of the minimal ter operon (terBCDEΔF) in resistance behavior of E. coli under environmental stress is evident.

This present study aims to investigate the potential prognostic values of dynactin genes (DCTN) for predicting the overall survival (OS) in low-grade glioma (LGG) patients.
The DCTN mRNA expression data were downloaded from The Cancer Genome Atlas database containing 518 patients with LGG. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for DCTN genes were performed by using Database for Annotation, Visualization, and Integrated Discovery platform, and their enrichment results were verified by using the Biological Networks Gene Ontology tool. Next, the correlations between DCTN genes and LGG were identified by Pearson correlation coefficient analysis. The OS was estimated by Kaplan-Meier survival analysis. The cBio Cancer Genomics Portal was used to analyze the mutations of DCTN genes and their effects on the prognosis of LGG. The correlation between the abundance of immune infiltration and tumor purity of DCTN genes were predicted by The Tumor Immune Estimation Resource.
Our research showed that the mRNA expression of DCTN4 in tumor tissues was much higher (P < 0.01) than that in normal tissues. Meanwhile, there was a certain correlation between the DCTN genes. Survival analysis showed that the high expression of DCTN1, DCTN3, DCTN4, DCTN6, and their co-expression were significantly correlated with favorable OS in LGG patients (P < 0.05). In DCTN2, a high mutation rate was observed. Further research showed that the genetic alteration in DCTN genes was related to a poor OS and progression-free survival of LGG patients. The expression of DCTN genes had a certain correlation with immune infiltrating cells.
Our study showed that the high expressions of DCTN1, DCTN3, DCTN4, and DCTN6 were associated with a favorable OS of LGG patients, indicating that these DCTN genes are potential biomarkers for evaluating the prognosis of LGG patients.

SARS-CoV-2 is mutating and creating divergent variants across the world. An in-depth investigation of the amino acid substitutions in the genomic signature of SARS-CoV-2 proteins is highly essential for understanding its host adaptation and infection biology. A total of 9587 SARS-CoV-2 structural protein sequences collected from 49 different countries are used to characterize protein-wise variants, substitution patterns (type and location), and major substitution changes. The majority of the substitutions are distinct, mostly in a particular location, and lead to a change in an amino acid\'s biochemical properties. In terms of mutational changes, envelope (E) and membrane (M) proteins are relatively more stable than nucleocapsid (N) and spike (S) proteins. Several co-occurrence substitutions are observed, particularly in S and N proteins. Substitution specific to active sub-domains reveals that heptapeptide repeat, fusion peptides, transmembrane in S protein, and N-terminal and C-terminal domains in the N protein are remarkably mutated. We also observe a few deleterious mutations in the above domains. The overall study on non-synonymous mutation in structural proteins of SARS-CoV-2 at the start of the pandemic indicates a diversity amongst virus sequences.

The high incidence of skin cancers in the Caucasian population is primarily due to the accumulation of DNA damage in epidermal cells induced by chronic ultraviolet B (UVB) exposure. UVB-induced DNA photolesions, including cyclobutane-pyrimidine dimers (CPDs), promote mutations in skin cancer driver genes. In humans, CPDs are repaired by nucleotide excision repair (NER). Several commonly used and investigational medications negatively influence NER in experimental systems. Despite these molecules\' ability to decrease NER activity in vitro, the role of these drugs in enhancing skin cancer risk is unclear. In this study, we investigated four molecules (veliparib, resveratrol, spironolactone, and arsenic trioxide) with well-known NER-inhibitory potential in vitro, using UVB-irradiated CHO epithelial and HaCaT immortalized keratinocyte cell lines. Relative CPD levels, hypoxanthine phosphoribosyltransferase gene mutation frequency, cell viability, cell cycle progression, and protein expression were assessed. All four molecules significantly elevated CPD levels in the genome 24 h after UVB irradiation. However, veliparib, spironolactone, and arsenic trioxide reduced the mutagenic potential of UVB, while resveratrol did not alter UVB-induced mutation formation. UVB-induced apoptosis was enhanced by spironolactone and arsenic-trioxide treatment, while veliparib caused significantly prolonged cell cycle arrest and increased autophagy. Spironolactone also enhanced the phosphorylation level of mammalian target of rapamycin (mTOR), while arsenic trioxide modified UVB-driven mitochondrial fission. Resveratrol induced only mild changes in the cellular UVB response. Our results show that chemically inhibited NER does not result in increased mutagenic effects. Furthermore, the UVB-induced mutagenic potential can be paradoxically mitigated by NER-inhibitor molecules. We identified molecular changes in the cellular UVB response after NER-inhibitor treatment, which may compensate for the mitigated DNA repair. Our findings show that metabolic cellular response pathways are essential to consider in evaluating the skin cancer risk-modifying effects of pharmacological compounds.

Multidrug-resistant tuberculosis (MDR-TB) poses a serious challenge to TB control. It is of great value to search for drug resistance mutation sites and explore the roles that they play in the diagnosis and prognosis of MDR-TB.
We consecutively enrolled MDR-TB patients from five cities in Jiangsu Province, China, between January 2013 and December 2014. Drug susceptibility tests of rifampin, isoniazid, ofloxacin, and kanamycin were routinely performed by proportion methods on Lowenstein-Jensen (LJ) medium. Drug resistance-related genes were sequenced, and the consistency of genetic mutations and phenotypic resistance was compared. The association between mutations and treatment outcomes was expressed as odds ratios (ORs) and 95% confidence intervals (CIs).
Among 87 MDR-TB patients, 71 with treatment outcomes were involved in the analysis. The proportion of successful treatment was 50.7% (36/71). The rpoB gene exhibited the highest mutation rate (93.0%) followed by katG (70.4%), pncA (33.8%), gyrA (29.6%), eis (15.5%), rrs (12.7%), gyrB (9.9%) and rpsA (4.2%). Multivariable analysis demonstrated that patients with pncA gene mutations (adjusted OR: 19.69; 95% CI: 2.43-159.33), advanced age (adjusted OR: 13.53; 95% CI: 1.46-124.95), and nonstandard treatment (adjusted OR: 7.72; 95% CI: 1.35-44.35) had a significantly higher risk of poor treatment outcomes.
These results suggest that Mycobacterium tuberculosis gene mutations may be related to phenotypic drug susceptibility. The pncA gene mutation along with treatment regimen and age are associated with the treatment outcomes of MDR-TB.

Hereditary breast and ovarian cancers are mainly linked to variants in BRCA1/2 genes. Recently, data has shown that identification of BRCA variants has an immediate impact not only in cancer prevention but also in targeted therapeutic approaches. This prospective observational study characterized the overall germline BRCA variant and variant of uncertain significance (VUS) frequency and spectrum in individuals affected by breast (BC) or ovarian cancer (OC) and in healthy individuals at risk by sequencing the entire BRCA genes. Of the 363 probands analyzed, 50 (13.8%) were BRCA1/2 mutated, 28 (7.7%) at BRCA1 and 23 (6.3%) at BRCA2 gene. The variant c.5266dupC p.(Gln1756Profs) was the most frequent alteration, representing 21.4% of the BRCA1 variants and 12.0% of all variants identified. The variant c.6313delA p.(Ile2105Tyrfs) of BRCA2 was the most frequent alteration observed in 6 patients. Interestingly, two new variants were identified in BRCA2. In addition, 25 different VUS were identified; two were reported for the first time in BRCA1 and two in BRCA2. The number of triple-negative BCs was significantly higher in patients with the pathogenic BRCA1/2-variant (36.4%) than in BRCA1/2 VUS (16.0%) and BRCA1/2 wild-type patients (10.7%) (p < 0.001). Our study reveals that the overall frequency of BRCA germline variants in the selected high-risk Italian population is about 13.8%. We believe that our results could have significant implications for preventive strategies for unaffected BRCA-carriers and effective targeted treatments such as PARP inhibitors for patients with BC or OC.

The dynamics of rare X-linked recessive traits is explored by simulation. The model follows the prevalence of affected males and carrier females as separate but correlated variables. Different mutation rates and selection coefficients are introduced for males and females. A virtual population based on a published study of hemophilia B in the west of Scotland is followed at weekly intervals over many years. Speculative values of critical parameters to mimic the real population are proposed.