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1.
Article in English | WPRIM | ID: wpr-925668

ABSTRACT

Purpose@#The value of the genomic profiling by targeted gene-sequencing on radiation therapy response prediction was evaluated through integrated analysis including clinical information. Radiation response prediction model was constructed based on the analyzed findings. @*Materials and Methods@#Patients who had the tumor sequenced using institutional cancer panel after informed consent and received radiotherapy for the measurable disease served as the target cohort. Patients with irradiated tumor locally controlled for more than 6 months after radiotherapy were defined as the durable local control (DLC) group, otherwise, non-durable local control (NDLC) group. Significant genomic factors and domain knowledge were used to develop the Bayesian Network model to predict radiotherapy response. @*Results@#Altogether, 88 patients were collected for analysis. Of those, 41 (43.6%) and 47 (54.4%) patients were classified as the NDLC and DLC group, respectively. Somatic mutations of NOTCH2 and BCL were enriched in the NDLC group, whereas, mutations of CHEK2, MSH2, and NOTCH1 were more frequently found in the DLC group. Altered DNA repair pathway was associated with better local failure–free survival (hazard ratio, 0.40; 95% confidence interval, 0.19 to 0.86; p=0.014). Smoking somatic signature was found more frequently in the DLC group. Area under the receiver operating characteristic curve of the Bayesian network model predicting probability of 6-month local control was 0.83. @*Conclusion@#Durable radiation response was associated with alterations of DNA repair pathway and smoking somatic signature. Bayesian network model could provide helpful insights for high precision radiotherapy. However, these findings should be verified in prospective cohort for further individualization.

2.
Article in English | WPRIM | ID: wpr-924992

ABSTRACT

The method of single-cell RNA sequencing has been rapidly developed, and numerous experiments have been conducted over the past decade. Their results allow us to recognize various subpopulations and rare cell states in tissues, tumors, and immune systems that are previously unidentified, and guide us to understand fundamental biological processes that determine cell identity based on single-cell gene expression profiles. However, it is still challenging to understand the principle of comprehensive gene regulation that determines the cell fate only with transcriptome, a consequential output of the gene expression program. To elucidate the mechanisms related to the origin and maintenance of comprehensive single-cell transcriptome, we require a corresponding single-cell epigenome, which is a differentiated information of each cell with an identical genome. This review deals with the current development of single-cell epigenomic library construction methods, including multi-omics tools with crucial factors and additional requirements in the future focusing on DNA methylation, chromatin accessibility, and histone post-translational modifications. The study of cellular differentiation and the disease occurrence at a single-cell level has taken the first step with single-cell transcriptome and is now taking the next step with single-cell epigenome.

3.
Journal of Breast Cancer ; : 162-170, 2020.
Article | WPRIM | ID: wpr-835605

ABSTRACT

Purpose@#Paclitaxel is a cytotoxic chemotherapy commonly used in patients with triple negative breast cancer (TNBC); however, the resistance to paclitaxel is a cause of poor response in the patients. The aim of this study was to examine the role of protein phosphatase 1H (PPM1H) in paclitaxel resistance in breast cancer patients. @*Methods@#To investigate the function of PPM1H in paclitaxel treatment, we conducted in vitro assays and molecular experiments using a stable cell line (MDA-MB-231) in which PPM1H is overexpressed. We also performed molecular analyses on patient tissue samples. Molecular expression related to PPM1H in breast cancer patients was analyzed using TCGA data. @*Results@#We investigated whether PPM1H was associated with paclitaxel resistance in breast cancer. PPM1H expression was upregulated in breast cancer cells treated with paclitaxel. We also observed that overexpression of PPM1H in breast cancer cells resulted in increased sensitivity to paclitaxel in vitro. Additionally, paclitaxel treatment induced dephosphorylation of cyclin-dependent kinase (CDK) inhibitor p27 (p27), which was more evident in PPM1H-overexpressing cells. To understand how upregulation of PPM1H increases paclitaxel sensitivity, we determined the levels of p27, phospho-p27, and CDK2, since CDK2 exerts antagonistic effects against PPM1H on p27 phosphorylation. The patient-derived xenograft (PDX) tumors that did not respond to paclitaxel showed increased levels of CDK2 and phospho-p27 and decreased levels of total p27 compared to the other breast tumor tissues. The use of dinaciclib, a selective CDK inhibitor, significantly inhibited tumor growth in the PDX model. @*Conclusion@#CDK2 kinase activity was significantly upregulated in basal breast cancer tumors and was negatively correlated with p27 protein levels in the TCGA breast cancer dataset, suggesting that targeting CDK2 may be an effective treatment strategy for TNBC patients.

4.
Article in English | WPRIM | ID: wpr-915016

ABSTRACT

Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies that has extremely heterogeneous clinical features and genetic background. The caveolin-3 gene (CAV3) is one of the causative genes. LGMD appears as a clinical continuum, from isolated skeletal muscle involvement to long QT syndrome. Here we report two patients without apparent muscle weakness in a family with CAV3 mutation.A 7-month-old Korean boy visited our muscle clinic because of an incidental finding of elevated serum creatine kinase (CK) concentration (680 IU/L, reference range, 20-270 IU/L) without clinical symptoms. The patient was born after an uneventful pregnancy and showed normal developmental milestones. He developed pseudohypertrophy of his calf muscle during the follow-up. We obtained a muscle biopsy at age 14 months, which showed size variations and degenerating/regenerating myofibers with endomysial fibrosis and immunohistochemical evidence of normal dystrophin. Under the impression of LGMD, we performed target panel sequencing and identified a heterozygous in-frame mutation of CAV3, c.307_312delGTGGTG (p.Val103_Val104del). Immunohistochemical staining of muscle indicated complete loss of caveolin-3 compared with normal control muscle, which supported the variant's pathogenicity. We performed segregation analysis and found that the patient's mother had the same variant with elevated serum CK level (972 IU/L).We report on autosomal dominant familial caveolinopathy caused by a pathogenic variant in CAV3, which was asymptomatic until the fourth decade. This case highlights the utility of next generation sequencing in the diagnosis of muscular dystrophies and the additive role of muscle biopsy to confirm the variants.

5.
Article in English | WPRIM | ID: wpr-719428

ABSTRACT

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.


Subject(s)
Academies and Institutes , Asians , DNA , Humans , Korea , Methods , Paraffin , Point Mutation , Precision Medicine , Prevalence
7.
Genomics & Informatics ; : 21-21, 2018.
Article in English | WPRIM | ID: wpr-714917

ABSTRACT

No abstract available.

8.
Safety and Health at Work ; : 180-183, 2018.
Article in English | WPRIM | ID: wpr-714880

ABSTRACT

BACKGROUND: This research investigates the degrees of slipperiness felt by the participants who walk on contaminants applied to a floor surface to decide degrees of slipperiness for various contaminants. METHODS: For the experiment, 30 participants walked on a floor to which six contaminants were applied. All participants took the analytic hierarchy process (AHP)–based slipperiness questionnaire survey for the six kinds of contaminants, and the results were compared with the coefficient of friction. RESULTS: The results of slip risk from the AHP indicate that grease is the most slippery of the six contaminants, followed by diesel engine oil, hydraulic oil, cooking oil, water-soluble cutting oil, and water in a decreasing order of slipperiness. When the results of slip risk from the AHP are compared with the static coefficient of friction for each contaminant, the order of slip risk follows the same trend. Although the results of slip risk from the AHP coincide with the static coefficient of friction, further study would be needed to investigate this relationship. CONCLUSION: This study will contribute as reference material for future research on preventing industrial accidents that result in falls from high places due to slipping.


Subject(s)
Accidental Falls , Accidents, Occupational , Cooking , Friction , Water
9.
Article in English | WPRIM | ID: wpr-212089

ABSTRACT

Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87–199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial–mesenchymal transition (EMT) process of sarcomatous components of GS. We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.


Subject(s)
Glioblastoma , Gliosarcoma , Humans , Prevalence , Prognosis
10.
Article in English | WPRIM | ID: wpr-655767

ABSTRACT

Mesenchymal stem cells (MSCs), which are multipotent and have self-renewal ability, support the regeneration of damaged normal tissue. A number of external stimuli promote migration of MSCs into peripheral blood and support their participation inwound healing. In an attempt to harness the potential beneficial effects of such external stimuli, we exposed human MSCs (hMSCs) to one such stimulus-low-dose ionizing radiation (LDIR)-and examined their biological properties. To this end, we evaluated differences in proliferation, cell cycle, DNA damage, expression of surface markers (CD29, CD34, CD90, and CD105), and differentiation potential ofhMSCs before and after irradiation with γ-rays generated using a ¹³⁷ CSirradiator.At doses less than 50 mGy, LDIR had no significant effect on the viability or apoptosis of hMSCs. Interestingly, 10 mGyofLDIR increased hMSC viability by 8% (p<0.001) comparedwith non-irradiatedhMSCs.At doses less than 50 mGy, LDIR did not induceDNA damage, including DNA strand breaks, or cause cellular senescence or cell-cycle arrest. Surface marker expression and in vitro differentiation potential of hMSCs were maintained after two exposures to LDIR at 10 mGy per dose. In conclusion, a two-dose exposure to LDIR at 10 mGy per dose not only facilitates proliferation of hMSCs, it alsomaintains the stem cell characteristics of hMSCswithout affecting their viability.These results provide evidence for the potential ofLDIRas an external stimulus for in vitro expansion of hMSCs and application in tissue engineering and regenerative medicine.


Subject(s)
Apoptosis , Cellular Senescence , Cell Proliferation , DNA , DNA Damage , Humans , In Vitro Techniques , Mesenchymal Stem Cells , Radiation, Ionizing , Regeneration , Regenerative Medicine , Stem Cells , Tissue Engineering
11.
Genomics & Informatics ; : 56-64, 2017.
Article in English | WPRIM | ID: wpr-93440

ABSTRACT

We have previously reported that NS-398, a cyclooxygenase-2 (COX-2)–selective inhibitor, inhibited replicative cellular senescence in human dermal fibroblasts and skin aging in hairless mice. In contrast, celecoxib, another COX-2–selective inhibitor, and aspirin, a non-selective COX inhibitor, accelerated the senescence and aging. To figure out causal factors for the senescence-modulating effect of the inhibitors, we here performed cDNA microarray experiment and subsequent Gene Set Enrichment Analysis. The data showed that several senescence-related gene sets were regulated by the inhibitor treatment. NS-398 up-regulated gene sets involved in the tumor necrosis factor β receptor pathway and the fructose and mannose metabolism, whereas it down-regulated a gene set involved in protein secretion. Celecoxib up-regulated gene sets involved in G2M checkpoint and E2F targets. Aspirin up-regulated the gene set involved in protein secretion, and down-regulated gene sets involved in RNA transcription. These results suggest that COX inhibitors modulate cellular senescence by different mechanisms and will provide useful information to understand senescence-modulating mechanisms of COX inhibitors.


Subject(s)
Aging , Animals , Aspirin , Celecoxib , Cellular Senescence , Cyclooxygenase 2 , Fibroblasts , Fructose , Gene Expression , Genes, vif , Humans , Mannose , Metabolism , Mice , Mice, Hairless , Oligonucleotide Array Sequence Analysis , RNA , Skin Aging , Tumor Necrosis Factor-alpha
12.
Article in English | WPRIM | ID: wpr-153372

ABSTRACT

Ethnically specific data on genetic variation are crucial for understanding human biology and for clinical interpretation of variant pathogenicity. We analyzed data obtained by deep sequencing 1303 Korean whole exomes; the data were generated by three independent whole exome sequencing projects (named the KOEX study). The primary focus of this study was to comprehensively analyze the variant statistics, investigate secondary findings that may have clinical actionability, and identify loci that should be cautiously interpreted for pathogenicity. A total of 495 729 unique variants were identified at exonic regions, including 169 380 nonsynonymous variants and 4356 frameshift insertion/deletions. Among these, 76 607 were novel coding variants. On average, each individual had 7136 nonsynonymous single-nucleotide variants and 74 frameshift insertion/deletions. We classified 13 pathogenic and 13 likely pathogenic variants in 56 genes that may have clinical actionability according to the guidelines of the American College of Medical Genetics and Genomics, and the Association for Molecular Pathology. The carrier frequency of these 26 variants was 2.46% (95% confidence interval 1.73–3.46). To identify loci that require cautious interpretation in clinical sequencing, we identified 18 genes that are prone to sequencing errors, and 671 genes that are highly polymorphic and carry excess nonsynonymous variants. The catalog of identified variants, its annotation and frequency information are publicly available (https://koex.snu.ac.kr). These findings should be useful resources for investigating ethnically specific characteristics in human health and disease.


Subject(s)
Biology , Clinical Coding , Exome , Exons , Genetic Variation , Genetics, Medical , Genomics , High-Throughput Nucleotide Sequencing , Humans , Pathology, Molecular , Virulence
13.
Article in English | WPRIM | ID: wpr-17711

ABSTRACT

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.


Subject(s)
Alzheimer Disease , Brain , Brain Injury, Chronic , Cell Line , Craniocerebral Trauma , Gene Expression Profiling , Humans , Models, Animal , Neurodegenerative Diseases , Phosphoprotein Phosphatases , Phosphotransferases , Sequence Analysis, RNA , Tauopathies , Transcriptome
14.
Article in English | WPRIM | ID: wpr-72758

ABSTRACT

This study aimed at constructing a draft genome of the adult female worm Toxocara canis using next-generation sequencing (NGS) and de novo assembly, as well as to find new genes after annotation using functional genomics tools. Using an NGS machine, we produced DNA read data of T. canis. The de novo assembly of the read data was performed using SOAPdenovo. RNA read data were assembled using Trinity. Structural annotation, homology search, functional annotation, classification of protein domains, and KEGG pathway analysis were carried out. Besides them, recently developed tools such as MAKER, PASA, Evidence Modeler, and Blast2GO were used. The scaffold DNA was obtained, the N50 was 108,950 bp, and the overall length was 341,776,187 bp. The N50 of the transcriptome was 940 bp, and its length was 53,046,952 bp. The GC content of the entire genome was 39.3%. The total number of genes was 20,178, and the total number of protein sequences was 22,358. Of the 22,358 protein sequences, 4,992 were newly observed in T. canis. Following proteins previously unknown were found: E3 ubiquitin-protein ligase cbl-b and antigen T-cell receptor, zeta chain for T-cell and B-cell regulation; endoprotease bli-4 for cuticle metabolism; mucin 12Ea and polymorphic mucin variant C6/1/40r2.1 for mucin production; tropomodulin-family protein and ryanodine receptor calcium release channels for muscle movement. We were able to find new hypothetical polypeptides sequences unique to T. canis, and the findings of this study are capable of serving as a basis for extending our biological understanding of T. canis.


Subject(s)
Adult , B-Lymphocytes , Base Composition , Classification , DNA , Female , Genome , Genomics , Humans , Larva Migrans, Visceral , Metabolism , Mucins , Peptides , Protein Structure, Tertiary , Receptors, Antigen, T-Cell , RNA , Ryanodine Receptor Calcium Release Channel , T-Lymphocytes , Toxocara canis , Toxocara , Transcriptome , Ubiquitin-Protein Ligases
15.
Yonsei Medical Journal ; : 872-878, 2016.
Article in English | WPRIM | ID: wpr-63338

ABSTRACT

PURPOSE: Lymphatic invasion (LI) is regarded as a predictor of the aggressiveness of ovarian cancer (OC). However, LI is not always the major determinant of long-term patient survival. To establish proper diagnosis and treatment for OC, we analyzed differentially expressed genes (DEGs) for patients with serous epithelial OC, with or without LI, who did or did not survive for 5 years. MATERIALS AND METHODS: Gene expression data from 63 patients with OC and LI, and 35 patients with OC but without LI, were investigated using an Affymetrix Human Genome U133 Array and analyzed using The Cancer Genome Atlas (TCGA) database. Among these 98 patients, 16 survived for 5 years or more. DEGs were identified using the Bioconductor R package, and their functions were analyzed using the DAVID web tool. RESULTS: We found 55 significant DEGs (p<0.01) from the patients with LI and 20 highly significant DEGs (p<0.001) from those without it. Pathway analysis showed that DEGs associated with carbohydrate metabolism or with renal cell carcinoma pathways were enriched in the patients with and without LI, respectively. Using the top five prognostic marker genes, we generated survival scores that could be used to predict the 5-year survival of patients with OC without LI. CONCLUSION: The DEGs identified in this study could be used to elucidate the mechanism of tumor progression and to guide the prognosis and treatment of patients with serous OC but without LI.


Subject(s)
Cystadenocarcinoma, Serous/genetics , Databases, Genetic , Female , Gene Expression Regulation, Neoplastic , Humans , Microarray Analysis , Middle Aged , Ovarian Neoplasms/genetics , Prognosis , Regression Analysis , Retrospective Studies , Survival Rate
16.
Article in English | WPRIM | ID: wpr-225574

ABSTRACT

During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV.


Subject(s)
Animals , Chlorocebus aethiops , Coronavirus Infections/diagnosis , Disease Outbreaks , Humans , Microscopy, Electron , Middle East Respiratory Syndrome Coronavirus/classification , Phylogeny , Polymerase Chain Reaction , RNA, Viral/analysis , Republic of Korea/epidemiology , Sequence Analysis, RNA , Vero Cells
17.
Genomics & Informatics ; : 62-68, 2016.
Article in English | WPRIM | ID: wpr-213648

ABSTRACT

Osteoporosis is a medical condition of global concern, with increasing incidence in both sexes. Bone mineral density (BMD), a highly heritable trait, has been proven a useful diagnostic factor in predicting fracture. Because medical information is lacking about male osteoporotic genetics, we conducted a genome-wide association study of BMD in Korean men. With 1,176 participants, we analyzed 4,414,664 single nucleotide polymorphisms (SNPs) after genomic imputation, and identified five SNPs and three loci correlated with bone density and strength. Multivariate linear regression models were applied to adjust for age and body mass index interference. Rs17124500 (p = 6.42 × 10⁻⁷), rs34594869 (p = 6.53 × 10⁻⁷) and rs17124504 (p = 6.53 × 10⁻⁷) in 14q31.3 and rs140155614 (p = 8.64 × 10⁻⁷) in 15q25.1 were significantly associated with lumbar spine BMD (LS-BMD), while rs111822233 (p = 6.35 × 10⁻⁷) was linked with the femur total BMD (FT-BMD). Additionally, we analyzed the relationship between BMD and five genes previously identified in Korean men. Rs61382873 (p = 0.0009) in LRP5, rs9567003 (p = 0.0033) in TNFSF11 and rs9935828 (p = 0.0248) in FOXL1 were observed for LS-BMD. Furthermore, rs33997547 (p = 0.0057) in ZBTB and rs1664496 (p = 0.0012) in MEF2C were found to influence FT-BMD and rs61769193 (p = 0.0114) in ZBTB to influence femur neck BMD. We identified five SNPs and three genomic regions, associated with BMD. The significance of our results lies in the discovery of new loci, while also affirming a previously significant locus, as potential osteoporotic factors in the Korean male population.


Subject(s)
Asians , Body Mass Index , Bone Density , Femur , Femur Neck , Genetics , Genome-Wide Association Study , Humans , Incidence , Linear Models , Male , Osteoporosis , Polymorphism, Single Nucleotide , Spine
18.
Genomics & Informatics ; : 126-131, 2015.
Article in English | WPRIM | ID: wpr-42762

ABSTRACT

Fulminant type 1 diabetes (T1DM) is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA) genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The HLA-DRB1*04:05-HLA-DQB1*04:01 haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009). A histidine residue at HLA-DRbeta1 position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI ,1.01 to 5.94; p = 0.054). Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.


Subject(s)
Autoimmunity , Exome , Genetic Predisposition to Disease , Genotype , Haplotypes , Glycated Hemoglobin A , Histidine , HLA Antigens , Humans , Hyperglycemia , Insulin , Ketosis , Leukocytes , Risk Factors
19.
Genomics & Informatics ; : 247-253, 2014.
Article in English | WPRIM | ID: wpr-113804

ABSTRACT

Osteosarcoma is the most common primary bone tumor, generally affecting young people. While the etiology of osteosarcoma has been largely unknown, recent studies have suggested that cyclooxygenase-2 (COX-2) plays a critical role in the proliferation, migration, and invasion of osteosarcoma cells. To understand the mechanism of action of COX-2 in the pathogenesis of osteosarcoma, we compared gene expression patterns between three stable COX-2-overexpressing cell lines and three control cell lines derived from U2OS human osteosarcoma cells. The data showed that 56 genes were upregulated, whereas 20 genes were downregulated, in COX-2-overexpressed cell lines, with an average fold-change > 1.5. Among the upregulated genes, COL1A1, COL5A2, FBN1, HOXD10, RUNX2, and TRAPPC2are involved in bone and skeletal system development, while DDR2, RAC2, RUNX2, and TSPAN31are involved in the positive regulation of cell proliferation. Among the downregulated genes, HIST1H1D, HIST1H2AI, HIST1H3H, and HIST1H4C are involved in nucleosome assembly and DNA packaging. These results may provide useful information to elucidate the molecular mechanism of the COX-2-mediated malignant phenotype in osteosarcoma.


Subject(s)
Cell Line , Cell Proliferation , Cyclooxygenase 2 , DNA Packaging , Gene Expression , Humans , Nucleosomes , Osteosarcoma , Phenotype
20.
Genomics & Informatics ; : 83-92, 2013.
Article in English | WPRIM | ID: wpr-74505

ABSTRACT

Genetic studies on facial morphology targeting healthy populations are fundamental in understanding the specific genetic influences involved; yet, most studies to date, if not all, have been focused on congenital diseases accompanied by facial anomalies. To study the specific genetic cues determining facial morphology, we estimated familial correlations and heritabilities of 14 facial measurements and 3 latent factors inferred from a factor analysis in a subset of the Korean population. The study included a total of 229 individuals from 38 families. We evaluated a total of 14 facial measurements using 2D digital photographs. We performed factor analysis to infer common latent variables. The heritabilities of 13 facial measurements were statistically significant (p < 0.05) and ranged from 0.25 to 0.61. Of these, the heritability of intercanthal width in the orbital region was found to be the highest (h2 = 0.61, SE = 0.14). Three factors (lower face portion, orbital region, and vertical length) were obtained through factor analysis, where the heritability values ranged from 0.45 to 0.55. The heritability values for each factor were higher than the mean heritability value of individual original measurements. We have confirmed the genetic influence on facial anthropometric traits and suggest a potential way to categorize and analyze the facial portions into different groups.


Subject(s)
Cues , Facial Bones , Factor Analysis, Statistical , Genetic Research , Humans , Orbit
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