Human Gene最新文献

Purpose

Micro-RNAs, play a significant role in regulating essential physiological processes by controlling post-transcriptional gene expression. Several disorders have been linked to variations in the miRNA genes that generate sequences of mature micro-RNA. The current research aims to determine if the genetic variations rs6505162; C > A in the MIR423 gene and rs11614913; T > C in the MIR196A2 gene are associated with type 2 diabetes mellitus (T2DM).

Method

The tetra-primers amplification refractory mutation system-polymerase chain reaction technique was used to identify these two single nucleotide polymorphisms (SNPs).

Results

The allele frequency of MIR423- rs6505162; C > A SNP was 0.47 for the wild allele (A) and 0.53 for the mutant allele (C) in the control group, while in the patients group the frequency was 0.54 and 0.46 for the A and C alleles respectively. No association was discovered between this SNP and T2DM (O.R = 0.75, P = 0.47 for AC genotype, and O.R = 0.53, P = 0.15 for CC genotype). The wild type of MIR196A2 rs11614913; C > T SNP showed a 100% prevalence in the study subjects, thus this SNP has no association with T2DM as well.

Conclusion

The current investigation demonstrates that the incidence of T2DM is not associated with the MIR196A2-rs11614913; C > T, and MIR423-rs6505162; C > A SNPs.

Background

Single Nucleotide Polymorphism (SNP)s in the genome and associated genes cause susceptibility to breast cancer, the most common cancer leading to death in women. Variation in different human races' genomes makes breast cancer prognosis challenging in terms of targeted drugs and therapies. The study aimed to compile the Breast cancer associated SNPs used for screening in the existing publications focusing Bangladeshi population, followed by the identification of Expression quantitative trait loci (eQTLs) associated with those SNPs from the eQTL database. eQTLs identify genes whose expression is regulated by specific SNPs. In silico characterization in terms of variant effect prediction, co-expression, Gene Ontology (GO) enrichment, protein-protein interaction, and sequence motif analysis narrowed down a specific set of candidate genes.

Methods

Published reports emphasizing the SNPs screened for Breast cancer in Bangladeshi population were analyzed in PancanQTL for identification of eQTLs which uses genotype and gene expression data from The Cancer Genome Atlas. The gene description and GO associated with identified eQTLs were retrieved from the Ensembl database and characterizations were performed using variant effect predictor, Coexpedia, MEME suite, and STRINGdb.

Results

It was found from the published reports that not all variants showed strong association with the disease in Bangladeshi population. The cis-eQTLs associated with reported SNPs tested so far on Bangladeshi population are ZNF575, MRPL42P5, C15orf57, C15orf62, NFATC3, XRCC1, C14orf153, CKB, BAG5, KLC1, MARK3. Among them only ZNF575 was enlisted as breast cancer associated eQTL and the rest are linked with other types of cancer. These genes are mostly associated in DNA-binding transcription factor activity, protein binding, Intracellular protein transport II, transferase activity. Protein-protein interaction could predict some functional partners to connect the eQTLs with respective SNP harboring genes. Taking the commonly screened genes for breast cancer as targets breast cancer associated cis and trans eQTLs along with the associated survival eQTLs have been retrieved from the database and a list of specific variants are recommended for future studies to get a more comprehensive scenario about the disease prognosis.

Conclusion

Since it was found from the existing literature that the commonly used variants are not always associated with all human races, this simple and precise in silico study was carried out to analyze publicly available data. This helped limit specific candidate genes and variants which will be helpful in future population-based screenings in understanding breast cancer prognosis with a provision to develop population specific personalized drug.

Background

Cockayne syndrome (CS) is a rare form of dwarfism that is characterized by progressive premature aging. The excision repair cross complementing protein group 6 (ERCC8) gene, which codes for the CS group A (CSA) protein, is usually mutated in cases of CS.

Method

We show two Iranian families who have significant speech delay, microcephaly, developmental delay, and notable growth failure. We have discovered a unique homozygous missense variant (c.742G > T) in CSA in an Iranian family with CS, which we discovered using whole exome sequencing as well.

Results

In two related probands, we found a homozygous variant (c.742G > T) in the ERCC8 gene that we believe to be a unique pathogenic mutation.

Conclusion

WES results together with the characteristic clinical manifestations of Cockayne syndrome, provided an accurate diagnosis for two families. Also, our study identified novel variants in Iranian families.

Background

Liquid biopsy (circulating cells and biomolecules) has revolutionized a non-invasive, efficient, and accurate alternative to tissue biopsy.

Aim

To investigate the diagnostic utility of circulating cell-free (cf) DNA levels and lung tissue-specific X(LunX) gene expression and its association with micrometastasis in non-small cell lung carcinoma (NSCLC) patients.

Methods

Blood (serum) samples of 81 NSCLC patients and matched 76 controls were collected, along with clinicopathological details. The cf-DNA was quantitated by amplifying β-globin and compared with the standard curve plotted by TaqMan control human genome DNA. LunX gene expression was measured by reverse transcription and SYBR Green chemistry-based real-time PCR. The relative fold was calculated by using the 2-^ΔΔCT method.

Results

The mean cf. DNA levels in NSCLC, lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) were significantly higher compared to controls (p < 0.0001). LunX gene expression was significantly higher in NSCLC (2.04-fold, p < 0.0001) and LUSC (1.90-fold, p < 0.0001); however, it slightly decreased in LUAD (1.31-fold, p < 0.0001) patients. With increased tumor size (T3 and T4), cf. DNA levels significantly increased (p < 0.0001). However, TNM was not associated with cf. DNA levels (p < 0.05). In contrast, LunX gene expression showed a higher fold with involvement of lymph nodes (N2; p = 0.015, N3; p = 0.009) and LunX 2-fold higher expression of LunX in metastasis (p = 0.0001). Smoking pack-year significantly influenced the levels of cf. DNA and LunX gene expression (p < 0.0001). There was no correlation between cfDNA levels and LunX gene expression (r = 0.06, p = 0.63). LunX demonstrated superior performance (AUC;0.886) with high sensitivity (100%) and specificity (62.96%). The cfDNA also showed good accuracy (AUC;0.729) but had a relatively low PPV.

Conclusion

LunX and cfDNA hold promise as potential non-invasive diagnostic biomarkers for NSCLC; however, LunX exhibited superior diagnostic performance in this study.

Breast cancer (BC) is recognized as the leading cause of death among women worldwide. The hippo signaling pathway is a tumor-suppressive pathway, that regulates organ size, and cell regeneration. Dysregulation of the hippo pathway by the epigenetic modulator, noncoding RNAs (ncRNA) including microRNA(miR) promotes tumorigenesis through many cellular processes, including over proliferation, apoptosis resistance, and cell migration. This study aimed to identify aberrantly expressed miR, associated pathways, and targeted genes in BC. Data of mostly studied miRs were obtained from the miR Cancer database and PubMed. In addition pathway analysis and target prediction of scrutinized miRs were performed by DIANA miRPath v.3.Further functional and enrichment analyses of selected miRs were performed by Gene ontology(GO) annotation tool in DIANA miRPath v.3.Total nine hundred fifteen studies were included for analysis from which 54 mostly studied miRs were identified. Pathway enrichment analysis showed that among 54 miRs, 40 miRs have been significantly associated with core components of the hippo pathway (p-0.00049).i.e. Salvador Family WW Domain-Containing Protein (SAV1), Mammalian STE20-like 1/2(MST1/2), Mps One Binder Kinase Activator Protein 1(MOB1A/B), Large Tumor Suppressor Kinase 1/2 (LATS1/2), Yes-Associated Protein (YAP1), Transcriptional Coactivator With PDZ-binding Motif (TAZ), TEA Domain Transcription Factor (TEAD). The top nine miRs that were strongly associated with these genes have been selected from 40 miRs. I.e. hsa-miR-22-3p, hsa-miR-181a-5p, hsa-let-7a-5p, hsa-miR-34a-5p, hsa-miR-335-5p, hsa-miR-182-5p, hsa-miR-20a-5p, hsa-miR-27a-3p, hsa- miR-335-3p. These miRs play a very important role in apoptosis, tumor development and metastasis, and the prognosis of BC. Hence, the interaction of these miRs with the hippo pathway would modulate the molecular mechanism of the hippo signaling pathway. Thus, experimental studies are required to demonstrate the microRNAs and their targeted genes of the hippo signaling pathway, provide new research ideas for the treatment and diagnosis of BC.

Background

Globally, the incidence of type 2 diabetes mellitus (T2DM) is rising at an alarming rate. Many studies have suggested the dysfunction of non-coding RNAs as pivotal regulators of gene expression in a wide range of illnesses, such as diabetes. The current study set out to investigate lncRNA metastasis-related lung adenocarcinoma transcript 1 (MALAT1), lncRNA plasmacytoma variant translocation 1 (PVT1), miR-214, and miR-9 expression in patients with diabetes, pre-diabetes, and healthy controls to determine if changes in these ncRNAs levels are reliable diagnostic, prognostic markers for T2DM. Additionally, we examined how these ncRNA levels correlate with the nuclear factor of the κ-light chain of enhancer-activated B cells (NF-κB) plasma levels.

Material and method

In this case-control investigation, participants (n = 150) were split evenly among healthy controls, type 2 diabetics, and prediabetics (n = 100/group). Real-time polymerase chain reaction (RT-PCR) was used to analyze lncRNA MALAT1, PVT1, miR-9, miR-214, and NF-κB. Furthermore, the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to discriminate the prediabetic group from the control group.

Result

MiR-214 and miR-9 levels are significantly decreased in T2DM and pre-diabetic patients compared to healthy controls (p < 0.05). In contrast, compared to healthy controls, MALAT1 and PVT1 expression levels rose progressively in pre-diabetic and T2DM subjects. Moreover, an inverse relationship was found between miR-214, miR-9 expression, and NF-κB. Additionally, by ROC curve analysis, miR-214, miR-9, MALAT1, and PVT1's AUC were measured to be 0.8687, 0.8256, 0.7861, and 0.8188.

Conclusion

These findings introduce the PVT1 / miR-214 / NF-κB and MALAT1 / miR-9 / NF-κB axis as critical players in T2DM pathogenesis.

Purpose

Childhood onset retinal dystrophies are heterogeneous group of diseases that include Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa, early onset retinitis pigmentosa (EORP) and Severe Early Childhood Onset Retinal Dystrophy (SECORD) and can present either as an isolated condition or with associated non-ocular features. Genetic testing aids in the differential diagnosis of these conditions, for monitoring and timely management of the systemic manifestations. In this study, we present a case series of childhood onset retinal dystrophies where genetic testing has aided in the diagnosis of syndromic form of inherited retinal degenerations (IRD).

Methods

Patients (N = 10) underwent complete ophthalmic examination including slit lamp biomicroscopy and dilated indirect ophthalmoscopy. ERG, fundus photograph and Optical Coherence Tomography was done for all patients if the child cooperated for the same. This was followed by targeted re-sequencing of IRD gene panel, on the Illumina Hiseq 2500 platform. Clinical follow up for other associated systemic features was advised based on the genetic results, for patients who were asymptomatic at the time of genetic diagnosis. The patients were monitored for the same periodically.

Results

Mutations were identified in IQCB1, ALMS1, SLC19A2, CNNM4, and VPS13B genes suggested associated syndromes. In all these cases, the ocular phenotype was the first presentation in early infancy and genetic testing for IRD genes suggested syndromic disease. The patients could hence be followed up appropriately for other manifestations.

Conclusions

Molecular diagnosis has helped in identifying the associated syndrome in these patients with childhood retinal dystrophies who were asymptomatic for some of the non-ocular features at the time of genetic testing. The patients can be benefitted by frequent clinical surveillance with a scope for effective and timely management of the systemic features wherever applicable.

By anchoring different cell structures like Z-bands, mitochondria, and desmosomes to the cytoskeleton, desmin filaments are essential for cellular integrity, signal transduction and mitochondrial function. The spectrum of clinical phenotypes associated with DES gene mutations is wide and heterogeneous. The most common clinical presentations of desminopathy include cardiomyopathy, cardiac conduction disease, and progressive skeletal myopathy. We present a case of an 11-year-old girl with progressive dilated cardiomyopathy (DCM) needing ECMO treatment. ECMO treatment was complicated by the early development of intracardiac thrombi and lung necrosis. Post-mortem exome sequencing revealed the causative, previously unreported, de novo mutation of DES gene, c.365 A > C, p.Tyr122Ser, characterized with unusually progressive clinical course leading to death.

Ductal adenocarcinoma of the pancreas(PDAC) is one of the malignancies with the worst prognosis still among solid tumors. Local and distant spread is observed at the time of diagnosis in a very significant part of patients. In recent years, significant improvements have been made in pancreatic cancer surgery, and serious decreases in morbidity and mortality rates have been detected, especially in specific centers. Studies on target gene therapy in all types of cancer, including pancreatic cancer, are very laborious and costly. For this reason, it provides convenience for research aimed at determining clinical markers by using bioinformatics software. In this study, it was aimed to determine the target gene and pathway by performing transcriptome analysis of 14 control and 28 PDAC data belonging to GSE123377 and GSE 163031. As a result of the analysis, it was found that 49 genes were in direct interaction with PDAC by determining the targets of 46 miRNAs with DIANA Path, whose expression differences were determined as a result of the analysis. Based on the PPI topological analysis, it was determined that 46 miRNAs of prostate cancer directly target 12 hub proteins (BRAF, STAT3,TGFBR1,SMAD2,SMAD3, TP53, TGFBR2, KRAS, MAPK1,MAPK3, MAPK8 and MAPK9). Functional Enrichment Analysis and biological process; cell communication with 59.18% and signal transmission with 73.47%; It was observed that protein serine/threonine kinase activity in molecular function was associated with a 22.45% effect on pathways. Thus, it is planned to support research by providing a system-level view by processing data networks for potential diagnostic biomarkers and target gene therapy for early diagnosis of PDAC.