Meta Gene最新文献

The combination of three different germline pathogenic variants: APC (NM_000038.5), PMS2 (NM_000535.5), PALB2 (NM_024675.3) in one individual has not been previously reported. In this brief report, we report an individual with the aforementioned autosomal dominant array of pathogenic variants. This individual was afflicted with stage IV colon cancer at age 31. The interaction of three separate germline pathogenic variants in determining cancer risk is not known; with the advent of widespread genetic panel testing, other multi-mutated genomes will surely be found and will have implications for treatment and surveillance.

Objectives

Previous observational studies evaluating the relationship of VEGFA rs2010963 polymorphism with cancer risk reported inconsistent outcomes. We conducted this meta-analysis to confirm a firm correlation of rs2010963 with overall cancers.

Materials and methods

A total of 70 eligible studies, including 25,245 cancer patients and 28,219 controls, were retrieved from online databases and included studies that analyzed odds ratio (OR) with 95% confidence intervals.

Results

In the overall cancers and population, no association between VEGFA rs2010963 and cancer was found. We observed a statistically significant association (p < 0.05) of rs2010963 with increased cancer risk in the African population (codominant 1: OR = 1.44, dominant model: OR = 1.41, allele model: OR = 1.24). Stratification by cancer types showed significant association with urogenital cancer risk under codominant 1 (OR = 1.22), codominant 2 (OR = 1.55), codominant 3 (OR = 1.24), dominant (OR = 1.29), recessive (OR = 1.36), and allele model (OR = 1.24). In renal cell cancer, four genetic models depicted significant correlation, namely codominant 1 (OR = 1.28), codominant 2 (OR = 1.68), dominant (OR = 1.38), and allele model (OR = 1.29). For osteosarcoma, codominant 3 (OR = 0.81) and the overdominant model showed significant association (OR = 1.16). Three genetic models showed a protective effect in thyroid cancer, including codominant 2, recessive, and allele models (OR = 0.48, 0.59, and 0.68, respectively). Only the recessive model in Asian breast cancer patients (OR = 1.16) and codominant 3 and recessive model in mixed patients (OR = 1.43 and 1.39) showed an association.In the overall cancers and population, no association between VEGFA rs2010963 and cancer was found.

Conclusions

The present meta-analysis indicates that VEGFA rs2010963 polymorphism is associated with susceptibility to cancer, especially in African population. Stratified analysis suggests that rs2010963 is also associated with osteosarcoma, urogenital, renal, thyroid, and breast cancer. Trial sequential analysis also validated our findings.

The male infertility accounts for about half of the infertility in couples. The idiotypic asthenospermia and oligospermia, which mostly occur as a result of genetic mutations, are among the main causes of male infertility. Until now, the relationship between different SNPs in the PRM1 gene and male infertility have been reported. In this study, we evaluated the possible correlation between 139C > A (rs737008) SNP in the PRM1 gene and asthenospermia/oligospermia in patients who referred to the Gerash Infertility Center. To aim this, three groups were considered in this study including healthy fertile males, asthenospermia patients and the patients suffering from oligospermia. After DNA extraction from their blood samples, the PCR was carried out to amplify a 558 bp PRM1 gene fragment. Then, the RFLP technique was performed to identified the SNP in the PCR products. Our results showed that the frequency of the 139C > A (rs737008) SNP in the population study was 41%. We found no significant differences between the SNP and asthenospermia/oligospermia in the current study. According to the demographic data, no significant differences were also found between smoking or alcohol consumption and male infertility in this study.

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease that leads to axon demyelination and white matter plaque formation. The aim of the present study is to inspect the association between single nucleotide polymorphisms (SNPs) of IL4 (rs2070874), IL17A (rs2275913), and IL33 (rs7044343) and MS predisposition. The genotyping of the three genetic variants was conducted through tetra-plex-based real-time polymerase chain reaction (T-plex RT-PCR) method combined with the SYBR green fluorescent dye. Sixty-eight Iraqi MS patients and fifty healthy individuals (controls) were enrolled, and their DNA was extracted from whole blood. The optimum annealing/extension temperature was set at 58 °C. For each SNP, allele-specific fragments were identified by their melting points generated through real-time PCR. Agarose gel electrophoresis was performed to confirm the results. The distribution of the IL4 SNP genotypes in patients and controls was in good agreement with Hardy-Weinberg equilibrium, while there was a skewness from Hardy-Weinberg equilibrium in patients' group for both IL17A and IL33 SNPs. Multinomial logistic regression analysis was performed to investigate the association between the studied variants under four genetic models (dominant, recessive, over-dominant, and co-dominant) and MS risk. However, there were no significant differences in genotype/allele frequencies of three SNPs between patients and controls. Taken together, our study indicated that genotype/allele of IL4 (rs2070874), IL17A (rs2275913), and IL33 (rs7044343) SNPs may not play a considerable role in the predisposition to MS in this sample of the Iraqi population. However, SYBR green-dependent T-plex RT-PCR can be a cost-effective, reproducible and simple method for genotyping SNPs of interest.

Physical exercise induces important system disturbances in the human body in a dose-response manner. Meta-analyses of genome-wide expression studies (GWES) might contribute to identify gene expression patterns and to a better understanding of the molecular mechanisms behind the complexity of adaptations to exercise, under a systems biology approach. Here, we aimed to analyze available data for human GWES that have evaluated the effect of exhaustive exercise in peripheral blood mononuclear cells (PBMC) and white blood cells (WBC). Three primary datasets retrieved from the NCBI Gene Expression Omnibus were meta-analyzed using a random effects model in the NetworkAnalyst software. After identifying nine differentially expressed genes (DEGs), we performed functional enrichment analyses to extract relevant biological information. A protein-protein interactions network on DEGs was built to evaluate the associated regulatory pathways. We found that five upregulated genes were members of the heat shock protein family, one of the top stress-response groups of genes. The enrichment analysis revealed key roles of the DEGs on the cellular adaptations to exercise-induced stress (i.e., temperature stimulus, topologically-incorrect and unfolded proteins). Our comparison analysis of DEG signatures found in blood cells with the expression pattern on muscle skeletal tissue showed some common genes. Thus, novel DEGs that might serve as hormetic mediators to exercise-induced adaptations were identified. Further experimental research is needed to validate these findings.

Background

Congenital heart diseases (CHDs) are believed to be caused by abnormal gene functioning during embryonic heart development. Transforming growth factor-beta1 (TGFB1) is known to express in the early embryonic heart and regulates heart development.

Methods

In this study, the coding region of TGFB1 was screened for 238 CHD patients by Sanger sequencing. Case-control association study was performed to identify the risk allele for CHD. In silico and in vitro approaches were used to elucidate the role of rare missense variant of TGFB1 using P19 cell line.

Results

We identified a rare missense variant (c.29C > G; p.P10R) in the signal peptide of the TGFB1 in two cases (MAF = 0.0042017), which was absent in 200 healthy controls. Although this variation is reported in the gnomAD (rs1800470, MAF =0.0002386) and the ExAC database (MAF = 0.00064), it is not reported in INDEX-db and GenomeAsia 100K databases. We also found three polymorphisms, namely c.29C > T; p.P10L, c.74G > C; p.R25P and c.788C > T; p.T263I. Case-control studies revealed that c.29C > T (rs1800470) variation is a risk factor, significantly associated with the CHD phenotype (OR = 1.4361, P = 0.0083). However, c.74G > C (rs1800471) and c.788C > T (rs1800472) alleles are not associated with the disease. Additionally, two rare synonymous variations, i.e. c.348C > T; p.T116T (MAF = 0.0042017) and c.501C > T; p.H167H (MAF = 0.00210084) were also identified in two and one cases, respectively. These were absent in the 200 controls. In silico analysis showed that missense variation p.P10R enhances the formation of the α-helix in the signal peptide, which possibly increases the TGFB1 secretion. The luciferase-reporter assay demonstrated significantly increased activity of p(SBE)₄ (P = 0.016) and p(CAGA)₁₂ (P = 0.0004) promoters in response to p.P10R mutant versus wild-type TGFB1.

Conclusion

The p.P10R variant of TGFB1 implicated a gain-of-function activity which is potentially deleterious, while the c.29C > T variation is a risk factor associated with the CHD.

Present-day forensic DNA analysis is witnessing a paradigm shift from size-based allele determination by capillary electrophoresis (CE) to sequence-based allele determination by Next Generation Sequencing (NGS). An attempt has been made to evaluate the sequence-based allelic data at two tri (D12ATA63, D22S1045), two tetra (D18S51, D1S1656), and two penta- (Penta D, Penta E) nucleotides repeat STR markers in the central Indian population. 183.33 times allele gain has been observed in D1S1656 after evaluating individual allelic sequences in comparison to the size-based alleles. Despite not witnessing any sequence-based allele gain, highest power of discrimination (0.978), Polymorphic Information Content (0.9), Power of Exclusion (0.807), typical paternity index (5.31), Expected heterozygosity (0.906), and lowest matching probability (0.022) was observed at Penta E marker suggesting its more usefulness among the considered markers for forensic and paternity applications. A giant leap in sequence-based allelic information showed a significant increase in forensic and paternity parameters (p = 0.646) in D1S1656. Substitution of TAGA with either TAGG or TAGC was found to be responsible for the generation of sequence variant alleles in D1S1656. Besides, the observation of rs4847015 SNP in 11.5% of sequences further increases the evidentiary value of D1S1656 in comparison to other STR markers analyzed in this study.

Osteoarthritis is a common orthopedic disease among the greatest causes of morbidity and disability worldwide; however, research on its pathogenesis and diagnostic methods remains limited. The present study focuses on analyzing the microarray dataset to elucidate the hub genes and pathways related to the osteoarthritis. The gene expression data was retrieved from GEO database (GSE169077) and differentially expressed genes were determined using GEO2R tool based on adjusted P-value and log2FC values based on which 27 genes were found to be significant of which 9 genes were up-regulated while 18 genes were down-regulated. This was followed by gene enrichment analysis identify the related Gene Ontology terms and pathways. The Protein-Protein Network is constructed with 15 nodes and 22 edges using STRING database and then exported to Cytoscape 3.8 to predict the hub genes. The hub genes identified are POSTN, COL1A2, COL1A1, BMP1, MXRA5, MMP13 and SERPINF1. The hub genes identified were not only found to be associated with bone related disorders but also few were involved in other diseases. Therefore targeting these genes for disease management could be a viable option in osteoarthritis.

Background: The renin–angiotensin system regulates the haemodynamics. ACE gene polymorphisms are known to influence serum angiotensin converting enzyme level. Contrast nephropathy develops after exposure to intravascular contrast media that influence vascular hemodynamics. ACE gene polymorpisms may have an enhancing role in contrast media related renal injury.

The aim of the study: The aim of this study was to investigate the impact of ACE insertion/deletion (I/D) polymorphism in contrast-induced nephropathy (CIN) development.

Methods: 194 patients with chronic kidney disease that were administered iodinated contrast media were examined. Patients were monitored for at least 7 days for CIN development after parenteral contrast exposure. Control and patient groups were divided in terms of CIN development status. Polymerase chain reaction was performed for the genotyping of the ACE gene polymorphism from DNAs that were isolated from peripheral blood of the patients.

Results: 83 patients with CIN (34 women, 49 men) and 111 control patients without CIN (43 women, 68 men) were enrolled. Gender was not statistically different between the two groups (p = 0.75). The average age of the CIN group (71) was greater than that of the control group (68). No association was detected between ACE gene polymorphism (II, ID AND DD genotypes) and CIN in both patients and controls.

Conclusion: ACE gene polymorphisms does not influence contrast induced nephropathy development.