Mahmood, Niaz;Moosa, Mahdi Muhammad;Matin, S. Abdul;Khan, Haseena
Interdisciplinary Bio Central
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제4권1호
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pp.1.1-1.7
/
2012
Background: The F-box proteins represent one of the largest families of proteins in eukaryotes. Apart from being a component of the ubiquitin (Ub)/26 S proteasome pathways, their regulatory roles in other cellular and developmental pathways have also been reported. One interesting feature of the genes encoding the proteins of this particular family is their variable selection patterns across different lineages. This resulted in the presence of lineage specific F-box proteins across different species. Findings: In this study, 48 non-redundant F-box proteins in E. siliculosus have been identified by a homology based approach and classified into three classes based on their variable C-terminal domains. A greater number of the F-box proteins have domains similar to the ones identified in other species. On the other hand, when the proteins having unknown or no C-terminal domain (as predicted by InterProScan) were analyzed, it was found that some of them have the polyglutamine repeats. To gain evolutionary insights on the genes encoding the F-box proteins, their selection patterns were analyzed and a strong positive selection was observed which indicated the adaptation potential of the members of this family. Moreover, four lineage specific F-box genes were found in E. siliculosus with no identified homolog in any other species. Conclusions: This study describes a genome wide in silico analysis of the F-box proteins in E. siliculosus which sheds light on their evolutionary patterns. The results presented in this study provide a strong foundation to select candidate sequences for future functional analysis.
Kim, Beom Su;Lee, Inchul;Yook, Jeong Hwan;Song, Kyuyoung;Kim, Byung-Sik
Journal of Gastric Cancer
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제20권2호
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pp.127-138
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2020
Purpose: Mucin 1 (MUC1) was identified as a gastric cancer (GC) susceptibility gene by genome-wide association studies in Asians and candidate gene studies in Europeans. This study aimed to investigate the association between the MUC1 rs4072037 polymorphism and GC in terms of the Lauren classification and long-term clinical outcomes. Materials and Methods: A total of 803 patients with GC and 816 unrelated healthy controls were enrolled in the study. The association between the MUC1 rs4072037 variant and GC histological types and clinical outcomes, including tumor recurrence and prognosis was investigated. Results: The major A allele of rs4072037 was associated with increased GC risk (P<0.05). In subtype analysis, the association was most significant for diffuse-type GC (P<0.05) and in a dominant model (P<0.05), whereas there was no association with intestinal-type GC (P>0.05). Cox proportional hazards analysis revealed the heterozygote AG rs4072037 allele as an independent risk factor influencing tumor recurrence and disease-related death in diffusetype GC (P<0.05). but not in intestinal-type GC (P>0.05). Conclusions: The exonic single nucleotide polymorphism rs4072037 in MUC1 was associated with diffuse-type GC and was an independent risk factor influencing tumor recurrence and disease-related death in diffuse-type GC.
Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein ($AFP{\geq}600$ IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.
Type VI secretion system (T6SS) has been discovered in a variety of gram-negative bacteria as a versatile weapon to stimulate the killing of eukaryotic cells or prokaryotic competitors. Type VI secretion effectors (T6SEs) are well known as key virulence factors for important pathogenic bacteria. In many Burkholderia species, T6SS has evolved as the most complicated secretion pathway with distinguished types to translocate diverse T6SEs, suggesting their essential roles in this genus. Here we attempted to detect and characterize T6SSs and potential T6SEs in target genomes of plant-associated and environmental Burkholderia species based on computational analyses. In total, 66 potential functional T6SS clusters were found in 30 target Burkholderia bacterial genomes, of which 33% possess three or four clusters. The core proteins in each cluster were specified and phylogenetic trees of three components (i.e., TssC, TssD, TssL) were constructed to elucidate the relationship among the identified T6SS clusters. Next, we identified 322 potential T6SEs in the target genomes based on homology searches and explored the important domains conserved in effector candidates. In addition, using the screening approach based on the profile hidden Markov model (pHMM) of T6SEs that possess markers for type VI effectors (MIX motif) (MIX T6SEs), 57 revealed proteins that were not included in training datasets were recognized as novel MIX T6SE candidates from the Burkholderia species. This approach could be useful to identify potential T6SEs from other bacterial genomes.
Park, Bo-Ruem;Ma, Jae-Kyung;Park, Kwang-Bum;Hong, Kyung-Won
대한의생명과학회지
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제23권2호
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pp.133-137
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2017
Periodontitis is the major causation of tooth loss in the elderly population. Multiple risk factors include oral microorganisms, smoking, metabolic syndrome, and genetic factors influence periodontitis development. In this study, we conducted a replication study of using previous Korean GWAS results by examining an independent population. The study population was recruited from Mir Dental Clinic, Daegu, Korea. In total, 93 samples were evaluated from July 2016 to January 2017. The sample groups include relatively older patients (>60 years) with no periodontitis (n = 31) and relatively younger patients (range 40~60 years) with severe periodontitis (n = 62). A total of seven markers which were previously reported to be associated with periodontitis were genotyped. Among the seven SNPs, rs16846206 and rs2392510 showed a significant association by logistic regression analysis and Chi square test, respectively. The former SNP showed significant association with severe periodontitis, whereas this study also showed same tendency in which individuals with the minor allele are significantly more frequent in cases than those in controls. The SNP is located on a coding gene (SLC9C2), where the alanine residue 505 is replaced by glycine (Ala505Gly). The later SNP was significant when differed between case and control groups, but there was no significance by logistic regression analysis when controlled for age and sex as covariant. Although the study population size examined in the current study was relatively smaller compared to previous studies, our results implicated that at least the two SNPs (rs16846206 and rs2392510) might be important candidates for the further genetic study.
Recently, several new methods for the detection of genetic damages in vitro and in vivo based on molecular biological techniques were introduced according to the rapid progress in toxicology combined with cellular and molecular biology. Among these methods, mouse lymphoma thymidine kanase (tk) gene forward mutation assay, single cell gel electrophoresis (comet assay) and transgenic animal and cell line model as a target gene of lac I (Big Blue) and lac Z (Muta Mouse) gene mutation are newly introduced based on molecular toxicological approaches. The mouse lymphoma tk$\^$+/-/ gene assay (MOLY) using L5178Y tk$\^$+/-/ mouse lymphoma cell line is one of the mammalian forward mutation assays, and has many advantages and more sensitive than hprt assay. The target gene of MOLY is a heterozygous tk$\^$+/-/ gene located in 11 chromosome, so it is able to detect the wide range of genetic changes like point mutation, deletion, rearrangement, and mitotic recombination within tk gene or deletion of entire chromosome 11. The comet assay is a rapid, simple, visual and sensitive technique for measuring and analysing DNA breakages in mammalian cells, Also, transgenic animal and cell line models, which have exogenous DNA incorporated into their genome, carry recoverable shuttle vector containing reporter genes to assess endogenous effects or alteration in specific genes related to disease process, are powerful tools to study the mechanism of mutation in vivo and in vitro, respectively. Also in vivo acridine orange supravital staining micronucleus assay by using mouse peripheral reticulocytes was introduced as an alternative of bone marrow micronucleus assay. In this respect, there was an International workshop on genotoxicity procedure (IWGTP) supported by OECD and EMS (Environmental Mutagen Society) at Washington D. C. in March 25-26, 1999. The objective of IWGTP is to harmonize the testing procedures internationally, and to extend to finalization of OECD guideline, and to the agreement of new guidelines under the International Conference of Harmonization (ICH) for these methods mentioned above. Therefore, we introduce and review the principle, detailed procedure, and application of MOLY, comet assay, transgenic mutagenesis assay and supravital staining micronucleus assay.
The effect of carbon dioxide on yeast growth was investigated during the cultivation of pH 5.0 and pH 6.8. by replacing the nitrogen part with carbon dioxide under aerobic conditions. The values of the specific growth rate under pH 5.0 and pH 6.8 conditions became 64.0% and 46.9%, respectively, compared to those before the change in gas composition. This suggests that the effect of carton dioxide was greater pronounced in pH 6.8 than in pH 5.0. The genome-wide transcriptional response to elevated carbon dioxide was examined using a DNA microarray. As for upregulated genes, it was noteworthy that 3 genes were induced upon entry into a stationary phase and 6 genes were involved in stress response. Of 53 downregulated genes, 22 genes were involved in the ribosomal biogenesis and assembly and 5 genes were involved in the lipid metabolism. These facts suggest that carbon dioxide could bring the cell conditions partially to a stationary phase. The ALD6 gene encoding for cytosolic acetaldehyde dehydrogenase was downregulated, which would lead to a lack of cell components for the growth. The downregulation of ALD6 was greater in pH 6.8 than in pH 5.0. consistent with physiological response. This suggests that it might be the most effective factor for growth inhibition.
Kim, Hyo-Young;Cho, Seo-Ae;Yu, Jeong-Mi;Sung, Sam-Sun;Kim, Hee-Bal
BMB Reports
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제43권8호
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pp.547-553
/
2010
Biochemical tests such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are useful for diagnosing patients with liver disease. In this study, we tested the association between copy number variation and the hepatic biomarkers AST and ALT based on 8,842 samples from population-based cohorts in Korea. We used Affymetrix Genome-Wide Human 5.0 arrays and identified 10,534 CNVs using HelixTree software. Of the CNVs tested using univariate linear regression, 100 CNVs were significant for AST and 16 were significant for ALT (P < 0.05). We identified 39 genes located within the CNV regions. DKK1 and HS3ST3B1 were shown to play roles in heparan sulfate biosynthesis and the Wnt signaling pathway, respectively. NAF1 and NPY1R were associated with glycoprotein processes and neuropeptide Y receptor activity based on GO categories. PTER, SOX14 and TM7SF4 were expressed in liver. DPYS and CTSC were found to be associated with dihydropyrimidinuria and Papillon-Lefevre syndrome phenotypes using OMIM. NPY5R was found to be associated with dyslipidemia using the Genetic Association Database.
Objectives: Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1), which was associated with central obesity-related traits via interactions with stress levels. We aimed to evaluate EBF1 gene-by-stress interaction effects on central adiposity traits, including visceral adipose tissue (VAT), in Korean adults. Methods: A total of 1467 Korean adults were included in this study. We selected 22 single-nucleotide polymorphisms (SNPs) in the EBF1 gene and analyzed their interactions with stress on central adiposity using additive, dominant, and recessive genetic modeling. Results: The four SNPs that had strong linkage disequilibrium relationships (rs10061900, rs10070743, rs4704967, and rs10056564) demonstrated significant interactions with the waist-hip ratio in the dominant model ($p_{int}$<0.007). In addition, two other SNPs (rs6556377 and rs13180086) were associated with VAT by interactions with stress levels, especially in the recessive genetic model ($p_{int}$<0.007). As stress levels increased, the mean values of central adiposity traits according to SNP genotypes exhibited gradual but significant changes (p<0.05). Conclusions: These results suggest that the common genetic variants for EBF1 are associated with central adiposity through interactions with stress levels, emphasizing the importance of managing stress in the prevention of central obesity.
Objectives : ICH breaks down blood vessels within the brain parenchyma, which finally leads to neuronal loss, drugs to treat ICH have not yet been established. In this experiment, we measured the effect of Woowhangchongshim-won (WWCSW) on intracerebral hemorrhage (ICH) in rat using microarray technology. Methods : We measured the effect of WWCSW on ICH in rat using microarray technology. ICH was induced by injection of collagenase type IV, and total RNA was isolated. Image files of microarray were measured using a ScanArray scanner, and the criteria of the threshold for up- and down-regulation was 2 fold. Hierarchical clustering was implemented using CLUSTER and TREEVIEW program, and for Ontology analysis. GOSTAT program was applied in which p-value was calculated by Chi square or Fisher's exact test based on the total array element. Results : WWCSW-treatment restored the gene expression altered by ICH-induction in brain to the levels of 76.0% and 70.1% for up- and down-regulated genes, respectively. Conclusion : Co-regulated genes by ICH model of rat could be used as molecular targets for therapeutic effects of drug including WWCSW. That is, the presence of co-regulated genes may represent the importance of these genes in ICH in the brain and the change of expression level of these co-regulated genes would also indicate the functional change of brain tissue.
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