687 results on '"Jong Il Kim"'
Search Results
152. Collagen VI-related myopathy: Expanding the clinical and genetic spectrum
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Byung Chan Lim, Anna Cho, Soo Yeon Kim, H.S. Kim, Woo Joong Kim, Sun Ah Choi, Se Song Jang, Jong Hee Chae, Ki Joong Kim, Jin Sook Lee, Jong Il Kim, and Si Houn Hahn
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Physiology ,Ullrich congenital muscular dystrophy ,Gene mutation ,medicine.disease_cause ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Collagen VI ,Physiology (medical) ,medicine ,Myopathy ,Genetic testing ,Mutation ,medicine.diagnostic_test ,business.industry ,Bethlem myopathy ,medicine.disease ,030104 developmental biology ,Congenital muscular dystrophy ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Introduction We aimed to analyze the clinical and genetic characteristics of collagen VI-related myopathy. Methods We analyzed the clinical course and mutation spectrum in patients with collagen VI gene mutations among our congenital muscular dystrophy cohort. Results Among 24 patients with mutations in collagen VI coding genes, 13 (54.2%) were categorized as Ullrich type, and 11 (45.8%) as non-Ullrich type. Congenital orthopedic problems were similarly observed in both types, yet multiple joint contractures were found only in the Ullrich type. Clinical courses and pathology findings varied between patients. Mutations in COL6A1, COL6A2, and COL6A3 were found in 15 (65%), 3 (13%), and 5 (22%) patients, respectively, without genotype-phenotype association. Five novel variants were detected. Discussion We verified clinical heterogeneity of collagen VI-related myopathy, which emphasizes the importance of genetic testing. Genotype-phenotype association or early predictors for progression were not identified. Multiple joint contractures predict rapid deterioration. Muscle Nerve 58: 381-388, 2018.
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- 2018
153. Evaluation of Structural Stability of Small Wind Turbine Blade by Blade Test and Structural Analysis and Improvement of Blade Design
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Youn Gi Choi, Shin You Kang, and Jong Il Kim
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Small wind turbine ,Materials science ,Blade (geometry) ,Structural stability ,business.industry ,Mechanical Engineering ,Composite blade ,Structural engineering ,Safety, Risk, Reliability and Quality ,business ,Industrial and Manufacturing Engineering ,Finite element method ,Tensile testing - Published
- 2018
154. Identification of African-Specific Admixture between Modern and Archaic Humans
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Jeffrey D. Wall, Aakrosh Ratan, Eric Stawiski, Hie Lim Kim, Changhoon Kim, Ravi Gupta, Kushal Suryamohan, Elena S. Gusareva, Rikky Wenang Purbojati, Tushar Bhangale, Vadim Stepanov, Vladimir Kharkov, Markus S. Schrӧder, Vedam Ramprasad, Jennifer Tom, Steffen Durinck, Qixin Bei, Jiani Li, Joseph Guillory, Samir Phalke, Analabha Basu, Jeremy Stinson, Sandhya Nair, Sivasankar Malaichamy, Nidhan K. Biswas, John C. Chambers, Keith C. Cheng, Joyner T. George, Seik Soon Khor, Jong-Il Kim, Belong Cho, Ramesh Menon, Thiramsetti Sattibabu, Akshi Bassi, Manjari Deshmukh, Anjali Verma, Vivek Gopalan, Jong-Yeon Shin, Mahesh Pratapneni, Sam Santhosh, Katsushi Tokunaga, Badrul M. Md-Zain, Kok Gan Chan, Madasamy Parani, Purushothaman Natarajan, Michael Hauser, R. Rand Allingham, Cecilia Santiago-Turla, Arkasubhra Ghosh, Santosh Gopi Krishna Gadde, Christian Fuchsberger, Lukas Forer, Sebastian Shoenherr, Herawati Sudoyo, J. Stephen Lansing, Jonathan Friedlaender, George Koki, Murray P. Cox, Michael Hammer, Tatiana Karafet, Khai C. Ang, Syed Q. Mehdi, Venkatesan Radha, Viswanathan Mohan, Partha P. Majumder, Sekar Seshagiri, Jeong-Sun Seo, Stephan Schuster, and Andrew S. Peterson
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Neanderthal ,Black People ,Archaic humans ,Genome ,Article ,03 medical and health sciences ,0302 clinical medicine ,biology.animal ,Genetics ,Animals ,Humans ,Denisovan ,Genetics (clinical) ,030304 developmental biology ,Neanderthals ,0303 health sciences ,biology ,Fossils ,Genome, Human ,Hominidae ,Gene Pool ,biology.organism_classification ,Homo floresiensis ,Geography ,Genetics, Population ,Evolutionary biology ,Identification (biology) ,Gene pool ,030217 neurology & neurosurgery ,Reference genome - Abstract
Recent work has demonstrated that two archaic human groups (Neanderthals and Denisovans) interbred with modern humans and contributed to the contemporary human gene pool. These findings relied on the availability of high-coverage genomes from both Neanderthals and Denisovans. Here we search for evidence of archaic admixture from a worldwide panel of 1,667 individuals using an approach that does not require the presence of an archaic human reference genome. We find no evidence for archaic admixture in the Andaman Islands, as previously claimed, or on the island of Flores, where Homo floresiensis fossils have been found. However, we do find evidence for at least one archaic admixture event in sub-Saharan Africa, with the strongest signal in Khoesan and Pygmy individuals from Southern and Central Africa. The locations of these putative archaic admixture tracts are weighted against functional regions of the genome, consistent with the long-term effects of purifying selection against introgressed genetic material.
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- 2019
155. A Study on Value Relevance of Mandatory Auditor Rotation Firm
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Jong Il Kim and Im Uni
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business.industry ,Relevance (law) ,Accounting ,Audit ,business ,Rotation (mathematics) ,Value (mathematics) ,Mathematics - Published
- 2018
156. Development of a common platform for the noninvasive prenatal diagnosis of X-linked diseases
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Ki Young Yoo, Seong Keun Yoo, Jong Hee Chae, Jeong-Sun Seo, Jong Yeon Shin, Jong Il Kim, Doyeong Hwang, Se Song Jang, and Byung Chan Lim
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0301 basic medicine ,Proband ,DNA Mutational Analysis ,Prenatal diagnosis ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Genotype ,medicine ,Humans ,Genetics (clinical) ,Recombination, Genetic ,Genetics ,Fetus ,Massive parallel sequencing ,Maternal Serum Screening Tests ,Haplotype ,Obstetrics and Gynecology ,Genetic Diseases, X-Linked ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female - Abstract
Objective The aim of this study was to develop a common targeted massively parallel sequencing platform for the noninvasive prenatal diagnosis (NIPD) of multiple X-linked diseases. Method The custom capture probe was designed to target 33 genes and recombination hotspots. We tested the carrier mother and male proband pair of 6 families. Plasma DNA of the pregnant carrier mother was collected at different gestational weeks and sequenced. The fetal genotype of each family was determined by estimating the imbalance between the 2 maternal haplotypes constructed using a common custom-designed platform. Results The targeted sequencing of the maternal, proband, and fetal genomic DNAs and maternal plasma DNAs resulted in uniform coverage across the target region. Three to 5 recombination points were observed in each sample. However, these recombination points did not affect the haplotype dosage analysis for fetal genotype prediction. Consequently, all fetal genotypes in the 6 families obtained from haplotype dosage analysis of maternal plasma sequencing data were predicted correctly. Conclusions Since a single platform that covers multiple diseases may prevent the need for disease-specific probes for the NIPD of individual disorders, this approach may provide a practical advantage for clinically implementing the NIPD of X-linked diseases.
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- 2018
157. Association between Sleep Duration and Osteoarthritis in Korean Adults Over 30 Years Old: The Sixth Korea National Health and Nutrition Examination Survey (2013-2015)
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Jong Il Kim, Hee Joo Lee, Rae Ho Chung, and Hyun Jin Kim
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Gerontology ,National Health and Nutrition Examination Survey ,business.industry ,Medicine ,Osteoarthritis ,business ,medicine.disease ,Association (psychology) ,Sleep duration - Published
- 2018
158. Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules From Thyroid Cancer
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Hoon Sung Choi, Nam H. Cho, S. Im, Chang Hwan Ryu, Ji Won Yoon, Ho Young Son, Min Joo Kim, Eun Kyung Lee, Soo Jung Kwak, Jeongseon Kim, Yul Hwangbo, Young Joo Park, You Jin Lee, and Jong Il Kim
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Adult ,Male ,0301 basic medicine ,Thyroid nodules ,medicine.medical_specialty ,Pathology ,Endocrinology, Diabetes and Metabolism ,Quantitative Trait Loci ,Thyroid Nuclear Factor 1 ,Clinical Biochemistry ,Population ,Thyroid Gland ,TRPM Cation Channels ,Genome-wide association study ,Context (language use) ,Biology ,Polymorphism, Single Nucleotide ,Biochemistry ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Gene Frequency ,Internal medicine ,Republic of Korea ,Biomarkers, Tumor ,Prevalence ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,Thyroid Neoplasms ,Thyroid Nodule ,education ,Thyroid cancer ,education.field_of_study ,Biochemistry (medical) ,Thyroid ,Middle Aged ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Expression quantitative trait loci ,Female ,Genome-Wide Association Study - Abstract
Context Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown. Objective To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer. Design and Setting We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data. Results The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10−8) and meta-analysis (OR, 1.28; P = 2.11 × 10−8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10−5; rs944289, P = 8.68 × 10−5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues. Conclusions To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.
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- 2018
159. Whole Genome Sequencing of Nontuberculous Mycobacterium (NTM) Isolates from Sputum and Environmental Specimens in Co-Habiting Patients with NTM Pulmonary Disease
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Jae-Joon Yim, Jong Il Kim, Jung-Ki Yoon, and Taek Soo Kim
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Whole genome sequencing ,medicine ,Sputum ,Pulmonary disease ,Biology ,medicine.symptom ,bacterial infections and mycoses ,Microbiology ,Nontuberculous mycobacterium - Abstract
Background : Nontuberculous mycobacterium (NTM) species are ubiquitous microorganisms. NTM pulmonary disease (NTM-PD) is caused not by human-to-human transmission but by independent environmental acquisition. However, recent studies using next-generation sequencing (NGS) have reported trans-continental spread of Mycobacterium abscessus among patients with cystic fibrosis. Results : We investigated NTM genomes through NGS to examine transmission patterns in three pairs of co-habiting NTM-PD patients who were suspected of patient-to-patient transmission. Three pairs of patients with NTM-PD co-habiting for at least 15 years were enrolled: a mother and a daughter with M. avium PD, a couple with M. intracellulare PD, and a second couple, one of whom was infected with M. intracellulare PD and the other of whom was infected with M. abscessus subsp. massiliense PD. Whole genome sequencing was performed using NTM colonies isolated from patients and environmental specimens. Genetic distances were estimated based on single nucleotide polymorphisms (SNPs) in the NTM genomes. Comparing SNPs in the consensus regions, the minimum pairwise SNP distances of NTM isolates derived from the two pairs of patients infected with the same NTM species were over 10,000. In phylogenetic analysis, the NTM isolates from patients with M. avium PD clustered with isolates from different environmental sources. Conclusions : In conclusion, considering the genetic distances between NTM strains, the likelihood of patient-to-patient transmission in pairs of co-habiting NTM-PD patients without overt immune deficiency is minimal.
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- 2019
160. CYP1A1 gene polymorphisms modify the association between PM10 exposure and lung function
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Hyun-Jin Kim, Belong Cho, Thomas M. Holsen, Ho Young Son, Yong-Seok Seo, Jong Il Kim, Philip K. Hopke, Jae Moon Yun, Hyuktae Kwon, Jin Ho Park, and Joohon Sung
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0301 basic medicine ,Vital capacity ,medicine.medical_specialty ,Environmental Engineering ,Health, Toxicology and Mutagenesis ,Physiology ,Single-nucleotide polymorphism ,010501 environmental sciences ,Biology ,01 natural sciences ,03 medical and health sciences ,FEV1/FVC ratio ,Polymorphism (computer science) ,Genotype ,Epidemiology ,medicine ,Environmental Chemistry ,Gene ,Lung function ,0105 earth and related environmental sciences ,Public Health, Environmental and Occupational Health ,General Medicine ,General Chemistry ,respiratory system ,Pollution ,respiratory tract diseases ,030104 developmental biology - Abstract
Genetic epidemiological studies have provided evidence that several genes modify the link between air pollution and lung function. We assessed whether the adverse impacts of particulate matter with an aerodynamic diameter ≤10 μm (PM10) on lung function are modified by CYP1A1 gene polymorphisms in Korean adults. We used health check-up data from 1817 men, and the annual mean concentrations of ambient PM10 estimated from the ambient data. Three single nucleotide polymorphisms (SNPs) of CYP1A1 were selected for our study. We identified significant CYP1A1 SNPs-by-PM10 interactions for forced expiratory volume 1 s (FEV1) and forced vital capacity (FVC) (all pint 0.05), whereas in heterozygous or homozygous alternate genotype groups, PM10 was significantly associated with decreased FEV1 (all passoc for FEV1
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- 2018
161. Comparative Genomics of Mycoplasma pneumoniae isolated from Children with Pneumonia: South Korea, 2010-2016
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Youbin Yeon, Jong Il Kim, Moon Woo Seong, Mi Seon Han, Dongjin Shin, Joon Kee Lee, Sung Im Cho, Sung Sup Park, and Eun Hwa Choi
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Mycoplasma pneumoniae ,lcsh:QH426-470 ,lcsh:Biotechnology ,Biology ,medicine.disease_cause ,Genome ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Bacterial Proteins ,INDEL Mutation ,lcsh:TP248.13-248.65 ,Pneumonia, Mycoplasma ,Republic of Korea ,Genetics ,medicine ,Humans ,Typing ,Child ,Epidemics ,Phylogeny ,030304 developmental biology ,Whole genome sequencing ,Comparative genomics ,0303 health sciences ,Phylogenetic tree ,030306 microbiology ,Genomics ,lcsh:Genetics ,Whole genome analysis ,Multilocus sequence typing ,GC-content ,Genome, Bacterial ,Biotechnology ,Research Article - Abstract
Background Mycoplasma pneumoniae is a common cause of respiratory tract infections in children and adults. This study applied high-throughput whole genome sequencing (WGS) technologies to analyze the genomes of 30 M. pneumoniae strains isolated from children with pneumonia in South Korea during the two epidemics from 2010 to 2016 in comparison with a global collection of 48 M. pneumoniae strains which includes seven countries ranging from 1944 to 2017. Results The 30 Korean strains had approximately 40% GC content and ranged from 815,686 to 818,669 base pairs, coding for a total of 809 to 828 genes. Overall, BRIG revealed 99% to > 99% similarity among strains. The genomic similarity dropped to approximately 95% in the P1 type 2 strains when aligned to the reference M129 genome, which corresponded to the region of the p1 gene. MAUVE detected four subtype-specific insertions (three in P1 type 1 and one in P1 type 2), of which were all hypothetical proteins except one tRNA insertion in all P1 type 1 strains. The phylogenetic associations of 30 strains were generally consistent with the multilocus sequence typing results. The phylogenetic tree constructed with 78 genomes including 30 genomes from Korea formed two clusters and further divided into two sub-clusters. eBURST analysis revealed two clonal complexes according to P1 typing results showing higher diversity among P1 type 2 strains. Conclusions The comparative whole genome approach was able to define high genetic identity, unique structural diversity, and phylogenetic associations among the 78 M. pneumoniae strains isolated worldwide.
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- 2019
162. Human Reference Genome and a High Contiguity Ethnic Genome AK1
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Seyoung Mun, Wooseok Lee, Kunhyung Bahk, Young-Kyung Bae, Jong Il Kim, Inchul Yang, Joohon Sung, Jeong-Sun Seo, Jooyeon Lee, Kyudong Han, Changhoon Kim, and Jina Kim
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chemistry.chemical_compound ,chemistry ,Evolutionary biology ,Contiguity ,Biology ,Genome ,DNA ,Human genetics ,Reference genome - Abstract
Studies have shown that the current human reference genome (GRCh38) might miss information for some populations, but “exactly what we miss” is still elusive due to the lower contiguity of non-reference genomes. We juxtaposed the GRCh38 with high contiguity genome assemblies, AK1, to show that ∼1.8% (∼53.4 Mbp) of AK1 sequences missed in GRCh38 with ∼0.76% (∼22.2 Mbp) of ectopic chromosomes. The unique AK1 sequences harbored ∼1,390 putative coding elements. We found that ∼5.3Mb (∼0.2%) of the AK1 sequences aligned and recovered the “unmapped” reads of fourteen individuals (5 East-Asians, 4 Europeans, and 5 Africans) as a reference. The regions that “unmapped” reads aligned included 110 common (shared between ≥2 individuals) and 38 globally (≥7 individuals) missing regions with 25 candidate coding elements. We verified that many of the common missing regions exist in multiple populations and chimpanzee’s DNA. Our study illuminates not only the discovery of missing information but the use of highly precise ethnic genomes in understanding human genetics.
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- 2019
163. Targeted linked-read sequencing for direct haplotype phasing of maternal DMD alleles: a practical and reliable method for noninvasive prenatal diagnosis
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Jong Il Kim, Se Song Jang, Jong Hee Chae, Jong Yeon Shin, Seong Keun Yoo, Byung Chan Lim, Ki Joong Kim, and Jeong-Sun Seo
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0301 basic medicine ,Proband ,congenital, hereditary, and neonatal diseases and abnormalities ,DNA Mutational Analysis ,Chorionic villus sampling ,lcsh:Medicine ,Prenatal diagnosis ,Polymorphism, Single Nucleotide ,Deep sequencing ,Dystrophin ,03 medical and health sciences ,Pregnancy ,Prenatal Diagnosis ,medicine ,Humans ,Allele ,lcsh:Science ,Alleles ,Genetic testing ,Genetics ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Haplotype ,lcsh:R ,High-Throughput Nucleotide Sequencing ,Muscular Dystrophy, Duchenne ,030104 developmental biology ,Haplotypes ,Mutation ,Amniocentesis ,Female ,lcsh:Q ,business - Abstract
For the noninvasive prenatal diagnosis (NIPD) of X-linked recessive diseases such as Duchenne muscular dystrophy (DMD), maternal haplotype phasing is a critical step for dosage analysis of the inherited allele. Until recently, the proband-based indirect haplotyping method has been preferred despite its limitations for use in clinical practice. Here, we describe a method for directly determining the maternal haplotype without requiring the proband’s DNA in DMD families. We used targeted linked-read deep sequencing (mean coverage of 692×) of gDNA from 5 mothers to resolve their haplotypes and predict the mutation status of the fetus. The haplotype of DMD alleles in the carrier mother was successfully phased through a targeted linked-read sequencing platform. Compared with the proband-based phasing method, linked-read sequencing was more accurate in differentiating whether the recombination events occurred in the proband or in the fetus. The predicted inheritance of the DMD mutation was diagnosed correctly in all 5 families in which the mutation had been confirmed using amniocentesis or chorionic villus sampling. Direct haplotyping by this targeted linked-read sequencing method could be used as a phasing method for the NIPD of DMD, especially when the genomic DNA of the proband is unavailable.
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- 2018
164. A Study of Cognitive Slips According to Contaminants on the Floor
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Jong-Il Kim, Min Soo Park, and Tae-gu Kim
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musculoskeletal diseases ,Engineering ,Analytic hierarchy process ,02 engineering and technology ,Slip (materials science) ,Diesel engine ,03 medical and health sciences ,0302 clinical medicine ,Grease ,Geotechnical engineering ,Safety, Risk, Reliability and Quality ,Coefficient of friction ,Slipping ,Chemical Health and Safety ,business.industry ,lcsh:Public aspects of medicine ,Public Health, Environmental and Occupational Health ,lcsh:RA1-1270 ,Contamination ,021001 nanoscience & nanotechnology ,body regions ,Hydraulic fluid ,0210 nano-technology ,business ,Safety Research ,030217 neurology & neurosurgery - 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. Keywords: AHP, Coefficient of friction, Contaminants, Slip accidents, Slipperiness
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- 2018
165. Aspects of urinary tract infections and antimicrobial resistance in hospitalized urology patients in Asia: 10-Year results of the Global Prevalence Study of Infections in Urology (GPIU)
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Hyun-Sop Choe, Seung-Ju Lee, Yong-Hyun Cho, Mete Çek, Zafer Tandoğdu, Florian Wagenlehner, Truls Erik Bjerklund-Johansen, Kurt Naber, Abolghasem Nikfallah, Adham Mohamad Kassem, Ahmed Khalil Aljubory, Ahmed Salman, Ainura Zarylbekovna Kutmanova, Akylbek Ch Usupbaev, Ala Eddin Daud Natsheh, Alexander Vladimirovich Andreychikov, Alexei Yurievich Plekhanov, Alexey Dmitrievich Vinokurov, Alexey Alexeevitch Dolgiy, Ali Taghizade Afshari, Ali Naghoni, Amitabh Dash, Andrey Vladimirovych Zaitcev, Anton Tsukanov, Anton Dashko, Anton I. Maliavin, Ardala Abdolghafouri Ghafouri, Arif Maqsood Ali, Arthur Grabsky, Aso Omer Rashed, Badrulhisham Bahadzor, Basuki B. Purnomo, Begench Gurbangeldiyevich Gadamov, Behrooz Rahnavardi Azari, Bongsuk Shim, Boris Vitalyevitch Berejanski, Brian Penero Blas, Chang Hee Han, Chang-Ho Lee, Chao Guan Xu, Chong Chien Ooi, Chu Leong The, Chul Sung Kim, Chuyen Vu Le, Daniel Landau, Deepak Babu Rauniyar, Dinyar Khazaeli, Doddy M. Soebadi, Donghoon Lim, Edmund Chiong, Egote Kofi Alexander, Ekaterina V. Kulchavenya, Elisaveta Asenova Draghijeva, Emad Rashad Mohamed Elsobky, Emad Eldin Khalid, Fahimeh Kazemi Rashed, Fiona Mei Wen Wu, Firuz Barakaev, Garnik Shahbazyan, Haitham Saeed Nakad, Hamid Reza Tajari, Hani R. Dahmash, Hasan S. Pliev, Hassan Mikhael Saloum, Hiromi Kumon, Hiroshi Kiyota, Hiroshi Hayami, Hisato Inatomi, Ho Jong Jeon, Hong Bin Kim, Hyun-Rim Lee, Ida Soo-fan Mah, Igor Artemovich Aboyan, InRae Cho, Iouri M. Essilevski, Iradj Khosropanah, Iskander Ilfakovich Abdullin, Ismail M. Hassan, Ivan S. Palagin, Jacob Kaneti, Jae Young Jeong, Jakhongir Fatikhovich Alidjanov, Jin-Bong Choi, Jong Il Kim, Jose-Vicente Tablante Prodigalidad, Joseph Philipraj Sebastian, Julia Makarycheva, Jun-Mo Kim, Kagan Felixovich Oleg, Kang-Jun Cho, null Karthi Keyan, Kazushi Tanaka, Kevin Lu, Khac Linh Tran Ngoc, Kiho Kim, Koichi Takahashi, Konstantin Antonovich Dunets, Lan Ru Zhu, Le Nguyen Vu, Levon Dm Arustamov, Liubov Alexandrovna Sinyakova, Lyidmila Pavlovna Barashova, M. Hammad Ather, Ma Yong, Madhav Harihar Waze, Maher Fawzi Zabaneh, Mahmood Reza Baghinia, Manoj Kumar Panigrahi, Maria Fe Raymundo Tayzon, Maroun Serhal, Mayad Nouma Moktash, Medhat Ahmad Mohammad Elsayed, Mehrdad Tahami, Michael Dan, Michael Yu Leh, Michail Frank, Mihir V. Baxi, Mikhail Josefovich Kogan, Ming Kui Wong, Mohamad Alsayed Habous, Mohamadali Aslmonadi, Mohamed Hani Abdulwahab Helal, Mohammad Salehi, Mohammad Kazem Moslemi, Mohammad Reza Moein, Mohammad Khalil Ibrahim Aldahiri, Msasanobu Tanimura, Mstislav Morozov Valentinovich, Muhammad Rafique, Mumtaz Ahmad, Muppidi Satyavani, Muthu Veeramani Veeramani, Nahed Ahmad Al Tabash, Naimet Kamal Alsaigh, Nayel Abdullah Altarwneh, Neelam Taneja, Nelson A. Cayco, Nguyen Dinh Xuong, Nguyen Phu Viet, Nguyen Van Tran, Nikolay Andreevich Vorobyov, Noor Nabi Junejo, Nourkhoda Sadeghifard, Nurbek Kytaibekovich, Oleg Nickolay Zuban, Paul Anthony Lugue Sunga, Perepanova Sergeevna Tamara, Polvonov Abror Aminovich, Prem Raj Gyawali, Quang Oanh Dao, Radman Abdullah Mohammed, Rahim Razavi Taghavi, Rajni Kapoor, Ramin Hakimzadeh, Rachhpal S. Singh, Raul Raz, Ravisankar Gopakumarapillai, Renu Bharadwaj, Reza aghelnezhad, Rinat Khammatov, Riyadh Al Salh, Roman Vladislavovich Gamazkov, Rosanna Tubo Santillan, Ryoichi Hamasuna, Saeid Arasteh, Saidamin Anvarovich Makhsudov, Sammy KK. Chan, Sang Don Lee, Sanjay Pandey, Satoshi Ishihara, Satoshi Takahashi, Sergey Vladislavovich Kotov, Seung Baik, Seung Chol Park, Seydali Eredjepov, Seyed Habibollah, Shashikant R. Bhange, Shigeru kosugi, Shin Jae Park, Shing-Hwa Lu, Siavash Falahatkar, Sobhan Ghafouryan, Starodoubtsevan Nadia Vladimirovna, Stephen Nazareth, Suchart Chaimuangraj, Sudhir Kumar Lokwani, Syed Johar Raza, Tahim Razavi Taghavi, Tahir Uddin Qazi, Takehiko Sho, Tamara Sergeevna Perepanova, Tamara Perepanova Sergeeuna, Taskeen Ahmad Khan, Tatyana Nikolaevna Moiseenko, Tawiz Gul, Teng Lung Lin, Teresita Tanaglin Gaviola, T.H. Kim, Thamara Wijesuriya, Thirumalai Ganesan, Tomohiro Ueda, U. Sin Ha, Vafa Abd Allahpour, Vitaly Eduardovich Aboyan, Vladimir Startsev, Waleed Ali Hasan, Walid Falou, Warli Syah Mirsya, Wasim Qasim, Wataru Nakamura, Wei Wang, WonYeol Cho, Xiaoming Huang, Yanwei Cao, Yasser Abd Elraouf Farahat, Yong Gil Na, Yoram Itchak Siegel, Youssef Moussa, and Zhang Xiangbo
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Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Imipenem ,Asia ,medicine.drug_class ,030106 microbiology ,Cephalosporin ,Antibiotics ,Urology ,Prevalence ,03 medical and health sciences ,Antibiotic resistance ,Levofloxacin ,Drug Resistance, Multiple, Bacterial ,Cystitis ,Escherichia coli ,Humans ,Medicine ,Pharmacology (medical) ,Escherichia coli Infections ,Aged ,Pyelonephritis ,business.industry ,Middle Aged ,Hospitals ,Anti-Bacterial Agents ,Ciprofloxacin ,Infectious Diseases ,Amikacin ,Urinary Tract Infections ,Female ,business ,medicine.drug - Abstract
Objectives To assess Asian data from Global Prevalence Study on Infections in Urology (GPIU study) which has been performed more than 10 years. Methods Seventeen Asian countries participated in the GPIU study between 2004 and 2013. Data for these countries were collected from the web-based GPIU database. The point prevalence of urinary tract infections (UTI) and antimicrobial susceptibility of representative pathogens were analysed for Asian geographic regions. Results A total of 6706 patients (5271 male, 1435 female) were assessed during the study period, and 659 patients were diagnosed with a UTI (9.8%). Of these UTI patients, 436 were male and 223 were female. Mean patient age was 54.9 ± 19.3 years. Pyelonephritis and cystitis were the most common clinical diagnoses, representing 30.7% and 29.9% of patients, respectively. Escherichia coli was the most frequently identified uropathogen (38.7%). For the patients with urinary tract infection, cephalosporins were the most frequently used antibiotics (34.4%), followed by fluoroquinolones (24.1%), aminoglycosides (16.8%). Fluoroquinolone resistance was relatively high (ciprofloxacin 54.9%, levofloxacin 39.0%), and cephalosporin resistance 42% (42.5–49.4%). Of the antibiotics evaluated, uropathogens had maintained the highest level of susceptibility to amikacin and imipenem (24.9% and 11.3% resistance rates, respectively). Conclusion Uropathogens in many Asian countries had high resistance to broad-spectrum antibiotics. Knowledge of regional and local resistance data and prudent use of antibiotics are important for proper management of UTI in Asian countries.
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- 2018
166. Valuation of the New Drug Biotechnology under Business Combinations : Based on Optional DCF Method
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Jong-Il Kim and Woo-Youn Jung
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Business combinations ,Actuarial science ,General Medicine ,Business ,Valuation (finance) - Published
- 2018
167. On the Problems of the Korean Regulation on Gambling Games based on the Game Industry Act
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Jong-Il Kim
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Game industry ,Advertising ,Business - Published
- 2018
168. Status of HCCR TBM program for DEMO blanket
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Soon Chang Park, Seungyon Cho, Jong-Il Kim, Eo Hwak Lee, Mu-Young Ahn, Bum Seok Kim, Young-Bum Chun, Seong Dae Park, Hyeong-Yeon Lee, Hyung Gon Jin, Dong Won Lee, Chang-Shuk Kim, Jae Sung Yoon, Young-Min Lee, Hyoseong Gwon, Suk-Kwon Kim, Duck Young Ku, Seok-Kwon Son, Cheol Woo Lee, Chang Wook Shin, Yi-Hyun Park, and Sunghwan Yun
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Integrated design ,Design stage ,Computer science ,business.industry ,Mechanical Engineering ,Nuclear engineering ,Fusion power ,Blanket ,01 natural sciences ,010305 fluids & plasmas ,Coolant ,Breeder (animal) ,Nuclear Energy and Engineering ,0103 physical sciences ,System integration ,General Materials Science ,010306 general physics ,business ,Civil and Structural Engineering - Abstract
Development of the Helium Cooled Ceramic Reflector (HCCR) breeding blanket is underway according to the development strategy of core technology for K-DEMO under the fusion energy development roadmap in Korea. The main goals are to validate integrated design tools and to develop core technologies in the field of materials, manufacturing and joining technologies, helium cooling and tritium technologies, system integration, and safety technologies. A unique graphite reflector concept was adopted to save cost by reducing the amount of beryllium neutron multiplier. The main functions and design concepts of the HCCR breeding blanket are to be verified in ITER through the HCCR Test Blanket Module (TBM) program. Not only breeder modules are to be tested in ITER but also the technologies of cooling, coolant purification, tritium extraction, etc. are to be tested or proved in ITER before employed in DEMO. This paper introduces the current updates of the design and R&D activities of the HCCR TBM systems in the preliminary design stage.
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- 2021
169. The Effect of Incentive and Labor Union on Financial Performance
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Jong Il Kim and Ki Wan Yoon
- Subjects
Labour economics ,Incentive ,Financial performance ,Economics ,General Medicine ,Labor union - Published
- 2017
170. Problems of Game Rating Policy in Korea and Proposal for Improvement
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Jong-Il Kim
- Subjects
030506 rehabilitation ,03 medical and health sciences ,Computer science ,0502 economics and business ,05 social sciences ,0305 other medical science ,050203 business & management - Published
- 2017
171. A Novel Combination Treatment Targeting BCL-XL and MCL1 for KRAS/BRAF-mutated and BCL2L1-amplified Colorectal Cancers
- Author
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Hansoo Park, Joo Young Kim, Ji Eun Lee, Seoyeon Min, Won-Suk Lee, Deukchae Na, Jeesoo Chae, Jinjoo Kang, Jee Yun Han, Ahra Lee, Jong Il Kim, Sung Yup Cho, Wonyoung Kang, and Charles Lee
- Subjects
0301 basic medicine ,Cancer Research ,Mutation ,biology ,Colorectal cancer ,Cancer ,Bcl-xL ,Disease ,medicine.disease ,medicine.disease_cause ,03 medical and health sciences ,030104 developmental biology ,Oncology ,In vivo ,medicine ,Cancer research ,biology.protein ,MCL1 ,KRAS - Abstract
Colorectal cancer is the third most commonly diagnosed cancer in the world, and exhibits heterogeneous characteristics in terms of genomic alterations, expression signature, and drug responsiveness. Although there have been considerable efforts to classify this disease based on high-throughput sequencing techniques, targeted treatments for specific subgroups have been limited. KRAS and BRAF mutations are prevalent genetic alterations in colorectal cancers, and patients with mutations in either of these genes have a worse prognosis and are resistant to anti-EGFR treatments. In this study, we have found that a subgroup of colorectal cancers, defined by having either KRAS or BRAF (KRAS/BRAF) mutations and BCL2L1 (encoding BCL-XL) amplification, can be effectively targeted by simultaneous inhibition of BCL-XL (with ABT-263) and MCL1 (with YM-155). This combination treatment of ABT-263 and YM-155 was shown to have a synergistic effect in vitro as well as in in vivo patient-derived xenograft models. Our data suggest that combined inhibition of BCL-XL and MCL1 provides a promising treatment strategy for this genomically defined colorectal cancer subgroup. Mol Cancer Ther; 16(10); 2178–90. ©2017 AACR.
- Published
- 2017
172. Impact of anesthetic agents on overall and recurrence-free survival in patients undergoing esophageal cancer surgery: A retrospective observational study
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Jun-Young Jo, Eun-Ho Lee, In-Cheol Choi, In-Jung Jun, Jong-Il Kim, Hyeong Ryul Kim, Wook-Jong Kim, and Ji-Hyun Chin
- Subjects
Male ,medicine.medical_specialty ,Surgical stress ,Esophageal Neoplasms ,lcsh:Medicine ,Disease-Free Survival ,Article ,03 medical and health sciences ,0302 clinical medicine ,030202 anesthesiology ,medicine ,Humans ,Anesthesia ,lcsh:Science ,Survival analysis ,Aged ,Anesthetics ,Proportional Hazards Models ,Retrospective Studies ,Multidisciplinary ,Proportional hazards model ,business.industry ,lcsh:R ,Cancer ,Retrospective cohort study ,Esophageal cancer ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,Treatment Outcome ,Intravenous anesthesia ,030220 oncology & carcinogenesis ,Anesthetic ,Multivariate Analysis ,Administration, Intravenous ,Female ,lcsh:Q ,business ,medicine.drug - Abstract
Given that surgical stress response and surgical excision may increase the likelihood of post-surgery cancer dissemination and metastasis, the appropriate choice of surgical anesthetics may be important for oncologic outcomes. We evaluated the association of anesthetics used for general anesthesia with overall survival and recurrence-free survival in patients who underwent esophageal cancer surgery. Adult patients (922) underwent elective esophageal cancer surgery were included. The patients were divided into two groups according to the anesthetics administered during surgery: volatile anesthesia (VA) or intravenous anesthesia with propofol (TIVA). Propensity score and Cox regression analyses were performed. There were 191 patients in the VA group and 731 in the TIVA group. In the entire cohort, VA was independently associated with worse overall survival (HR 1.58; 95% CI 1.24–2.01; P P = 0.003) after multivariable analysis adjustment. Similarly, in the propensity score matched cohorts, VA was associated with worse overall survival (HR 1.45; 95% CI 1.11–1.89; P = 0.006) and recurrence-free survival (HR 1.44; 95% CI 1.11–1.87; P = 0.006). TIVA during esophageal cancer surgery was associated with better postoperative survival rates compared with volatile anesthesia.
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- 2017
173. Improvement of Online Game Use Restriction System
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법학박사 NHN엔터테인먼트(주) 대외협력실 이사 and Jong-Il Kim
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business.industry ,Computer science ,Internet privacy ,business ,Paternalism - Published
- 2017
174. Analysis of Private Company Stock Valuation under Enforcement Regulations for Issuance and Disclosure of Securities
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Hong Seok Jang and Jong Il Kim
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Finance ,business.industry ,Stock valuation ,business ,Enforcement - Published
- 2017
175. A critical review on theory and methodology of archaeology in nationalism
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Jong Il Kim
- Subjects
Anthropology ,Sociology ,Archaeology ,Nationalism - Published
- 2017
176. CDH13 gene-by-PM10 interaction effect on lung function decline in Korean men
- Author
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Jae Moon Yun, Hyuktae Kwon, Jin Young Min, Yong-Seok Seo, Jin Ho Park, Joohon Sung, Kyoung-Bok Min, Jong Il Kim, Hyun-Jin Kim, and Belong Cho
- Subjects
0301 basic medicine ,Vital capacity ,Environmental Engineering ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Physiology ,Single-nucleotide polymorphism ,General Medicine ,General Chemistry ,010501 environmental sciences ,Biology ,01 natural sciences ,Pollution ,respiratory tract diseases ,03 medical and health sciences ,FEV1/FVC ratio ,030104 developmental biology ,Genotype ,Environmental Chemistry ,SNP ,Gene–environment interaction ,Gene ,0105 earth and related environmental sciences ,Genetic association - Abstract
Lung function can be influenced by genetic factors, which may explain individual differences in susceptibility to the effects of air pollution. This study investigated whether the effect of particulate matter with an aerodynamic diameter ≤10 μm (PM10) on lung function is modified by Cadherin 13 (CDH13) genetic variants in Korean men. This study included a total of 1827 men who were recruited from two health check-up centers, and the annual average PM10 concentrations were used. A total of 200 single-nucleotide polymorphisms (SNPs) of the CDH13 gene were selected for this study. We found that a SNP in CHD13 intron, rs1862830, had the strongest associations with both forced expiratory volume in 1 s (FEV1) (pint = 1.90 × 10−4) and forced vital capacity (FVC) (pint = 1.88 × 10−3) by interacting with PM10 in a recessive model. A stratified association analysis according to this SNP showed that PM10 in the AG or GG genotype group was not significantly associated with either FEV1 or FVC, whereas in homozygous risk-allele carriers (AA), FEV1 and FVC decreased significantly (by 3.8% and 3.1%, respectively) per 10 μg/m3 of increase in PM10 concentration. This pattern was also reproducible in the independent subgroups that were classified according to recruitment site. The present study replicated the CDH13 gene-by-PM10 interaction effect on lung function at the gene level, revealing that a genetic variant of CDH13 modified the relationship between PM10 and lung function decline in Korean men.
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- 2017
177. A Study on Selecting Personal Protective Equipment for Listed Hazardous Chemicals (2): Analysis Using an Exposure Risk Matrix
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Don-Hee Han, Sang-Tae Chung, Jong-Il Kim, Chung-Soo Lee, and Yong-Sung Cho
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03 medical and health sciences ,Engineering ,0302 clinical medicine ,Risk analysis (engineering) ,business.industry ,Hazardous waste ,Environmental health ,030212 general & internal medicine ,business ,030210 environmental & occupational health ,Personal protective equipment ,Risk matrix - Published
- 2016
178. A Study on Selecting Personal Protective Equipment for Listed Hazardous Chemicals (1): Analysis of Hazard Ranks and Workplace Exposure Risks
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Jong-Il Kim, Yong-Sung Cho, Don-Hee Han, Sang-Tae Chung, and Chung-Soo Lee
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Engineering ,business.industry ,Hazardous waste ,Environmental health ,business ,Personal protective equipment ,Hazard - Published
- 2016
179. Clinical whole exome sequencing in early onset diabetes patients
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Jong Il Kim, Soo Heon Kwak, Chang Ho Ahn, Jungsun Park, Jeesoo Chae, Kyong Soo Park, Hye Seung Jung, Dae Ho Lee, Young Min Cho, and Chan hyeon Jung
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Adult ,Male ,0301 basic medicine ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Bioinformatics ,ABCC8 ,Maturity onset diabetes of the young ,Young Adult ,03 medical and health sciences ,Endocrinology ,Asian People ,Diabetes mellitus ,Republic of Korea ,Internal Medicine ,medicine ,Humans ,Exome ,Genetic Testing ,Exome sequencing ,Genetic testing ,Genetics ,Massive parallel sequencing ,biology ,medicine.diagnostic_test ,business.industry ,High-Throughput Nucleotide Sequencing ,General Medicine ,Middle Aged ,medicine.disease ,HNF1A ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,biology.protein ,Female ,business - Abstract
Aims There could be an overlap of monogenic diabetes and early onset type 2 diabetes in those who are diagnosed before age of 30years. Genetic diagnosis in these patients might improve the quality of care. A limited number of studies have used whole exome sequencing (WES) in Asian patients with early onset diabetes, and the clinical utility of WES is largely unknown. Methods We performed whole exome capture and massive parallel sequencing in 28 patients with early onset diabetes. Those who had a strong family history of diabetes were preferentially enrolled. Rare and non-silent variants in 29 genes known to cause monogenic diabetes, including 12 maturity-onset diabetes of the young (MODY) genes, were investigated for pathogenicity. Results The average depth of on-target WES reads was 97 X. A total of four pathogenic or likely pathogenic rare missense variants (p.Leu319Pro in HNF4A , p.His103Tyr and p.Arg74Gln in ABCC8 , and p.Leu139Val in HNF1A ) in MODY genes were identified in three patients. Although four rare non-silent variants in MODY genes (p.Arg183Cys in PAX4 , p.Val139Ile and p.Pro740fs in CEL , and p.Val147Ile in HNF4A ) and two rare non-silent variants in monogenic diabetes genes (p.Glu169Lys in WFS1 , and p.Pro407Gln in GATA4 ) were identified, their pathogenicity was uncertain or likely benign. Conclusions WES could be an initial option for genetic testing in patients with early onset diabetes. However, sufficient and universal coverage of genes of interest is required. In addition, it could be difficult to interpret variant pathogenicity, and these cases might require further validation.
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- 2016
180. Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma
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Hae Yong Yoo, Young Hyeh Ko, Seung-Bok Lee, Won Seog Kim, Jong Il Kim, Seok Jin Kim, and Ha Young Park
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,DNA Copy Number Variations ,Bioinformatics ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Missense mutation ,Refractory Diffuse Large B-Cell Lymphoma ,Exome ,FANCL ,whole exome ,business.industry ,sequencing ,Genes, p53 ,medicine.disease ,diffuse large B cell lymphoma ,Lymphoma ,refractory ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Lymphoma, Large B-Cell, Diffuse ,Gene Fusion ,business ,Diffuse large B-cell lymphoma ,Research Paper ,Biomedical sciences - Abstract
// Ha Young Park 1, 2 , Seung-Bok Lee 3 , Hae-Yong Yoo 4 , Seok-Jin Kim 5 , Won-Seog Kim 5 , Jong-Il Kim 1 , Young-Hyeh Ko 2 1 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 03080, Republic of Korea 2 Department of Pathology, Samsung Medical Center, SungKyunKwan University, Seoul, 06351, Republic of Korea 3 Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, 03080, Republic of Korea 4 Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea 5 Section of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sung Kyun Kwan University, 06351, Republic of Korea Correspondence to: Young-Hyeh Ko, email: yhko310@skku.edu Jong-Il Kim, email: jongil@snu.ac.kr Keywords: diffuse large B cell lymphoma, refractory, whole exome, transcriptome, sequencing Received: August 31, 2016 Accepted: October 28, 2016 Published: November 09, 2016 ABSTRACT Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although rituximab therapy improves clinical outcome, some patients develop resistant DLBCL; however, the genetic alterations in these patients are not well documented. To identify the genetic background of refractory DLBCL, we conducted whole-exome sequencing and transcriptome sequencing for six patients with refractory and seven with responsive DLBCL. The average numbers of pathogenic somatic single nucleotide variants and indels in coding regions were 71 in refractory patients (range 28–120) and 38 (range 19–66) in responsive patients. Missense mutations of TP53 were exclusive in 50% (3/6) of refractory patients and involved the DNA-binding domain of TP53 . All missense mutations of TP53 were accompanied by copy number deletions. RAB11FIP5, PRKCB, PRDM15, FNBP4, AHR, CEP128, BRE, DHX16, MYO6, and NMT1 mutations were recurrent in refractory patients. MYD88 , B2M , SORCS3 , and WDFY3 mutations were more frequent in refractory patients than in responsive patients. REL – BCL11A fusion was found in two refractory patients; one had both fusion and copy number gain. Recurrent copy gains of POU2AF1, SLC1A4, REL11, FANCL, CACNA1D, TRRAP, and CUX1 with significantly increased average expression were found in refractory patients. The expression profile revealed enriched gene sets associated with treatment resistance, including oxidative phosphorylation and ATP-binding cassette transporters. In conclusion, this study integrated both genomic and transcriptomic alterations associated with refractory DLBCL and found several treatment-resistance alterations that may contribute to refractoriness.
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- 2016
181. Dysregulated Wnt signalling and recurrent mutations of the tumour suppressorRNF43in early gastric carcinogenesis
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Min Jung Kim, Gibeom Park, Jeesoo Chae, Sung Jin Kim, Byung-Hoon Min, Michael Van Vrancken, Nayoung K.D. Kim, Jong Il Kim, Jinha Hwang, Ha Young Park, Se Song Jang, Changho Park, Soomin Ahn, Sangjeong Ahn, Yun Kyung Lee, Sang Yun Ha, Kyoung-Mee Kim, So Young Kang, Ryoji Kushima, and Young Ho Kim
- Subjects
0301 basic medicine ,Mutation ,Adenoma ,education ,Wnt signaling pathway ,Cancer ,Biology ,medicine.disease ,medicine.disease_cause ,Bioinformatics ,digestive system diseases ,Pathology and Forensic Medicine ,Early Gastric Cancer ,Malignant transformation ,03 medical and health sciences ,030104 developmental biology ,Germline mutation ,Dysplasia ,medicine ,Cancer research - Abstract
Several recurrent mutations and epigenetic changes have been identified in advanced gastric cancer, but the genetic alterations associated with early gastric carcinogenesis and malignant transformation remain unclear. We investigated the genomic and transcriptomic landscape of adenomas with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and intestinal-type early gastric cancer (EGC). The results were validated in an independent cohort that included EGCs directly adjacent to adenoma (EGC-adenomas) that were in the process of malignant transformation, and de novo EGCs that do not seem to have been derived from adenoma. The expression patterns clearly divided into normal, LGD, and EGC, whereas those of HGD overlapped with LGD or EGC. These results suggest that HGD is the critical stage determining malignant transformation. We found that genes related to focal adhesion and extracellular matrix receptor interaction pathways were upregulated as LGD progressed to EGC, whereas canonical Wnt signalling and peroxisome proliferator-activated receptor (PPAR) signalling pathway genes were downregulated in EGC. Genomic alterations such as somatic mutation, gene fusion and copy number variation increased gradually from LGD to EGC. APC mutations were present in 67% of LGDs, 58% of HGDs, and 18% of EGCs. RNF43 mutations were present only in HGD and EGC, and TP53 mutations were present only in EGC. In a validation cohort, RNF43 mutations were present in 35.2% of EGC-adenomas, but in only 8.6% of de novo EGCs. This is the first study to investigate the genomic and transcriptomic landscape of multistep gastric carcinogenesis. We investigated important alterations and their related pathways in each step as tumours progressed from LGD to HGD and eventually to EGC. We suggest that mutations and downregulation of RNF43 may play a critical role in the transition from adenoma to carcinoma. Given these findings and Wnt dependency in tumours with RNF43 mutation, intestinal-type gastric cancer or adenoma with RNF43 mutation might represent a promising indication for Wnt-targeted agents. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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- 2016
182. A copy number variation in PKD1L2 is associated with colorectal cancer predisposition in korean population
- Author
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Hee Jung Son, Hey Mi Jung, Jin Ho Park, Young-Ho Kim, Duk-Hwan Kim, Dong Sung Lee, Belong Cho, Hee Cheol Kim, Jong Il Kim, Seungbok Lee, Sung Noh Hong, Changho Park, Mingon Kang, Joohon Sung, Seong Jin Kim, and Tae Jun Kim
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,Cancer ,Subgroup analysis ,medicine.disease ,Bioinformatics ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Copy-number variation ,business ,Survival rate ,Body mass index ,Comparative genomic hybridization ,Genetic association - Abstract
Recently reported genome-wide association studies have identified more than 20 common low-penetrance colorectal cancer (CRC) susceptibility loci. Recent studies have reported that copy number variations (CNVs) are considered important human genomic variants related to cancer, while the contribution of CNVs remains unclear. We performed array comparative genomic hybridization (aCGH) in 36 CRC patients and 47 controls. Using breakpoint PCR, we confirmed the breakpoint of the PKD1L2 deletion region. High frequency of PKD1L2 CNV was observed in CRC cases. We validated the association between PKD1L2 variation and CRC risk in 1,874 cases and 2,088 controls (OR=1.44, 95% CI=1.04-1.98, P=.028). Additionally, PKD1L2 CNV is associated with increased CRC risk in patients younger than 50 years (OR=2.14, 95% CI 1.39-3.30, P=5.8x10-4). In subgroup analysis according to body mass index (BMI), we found that the CN loss of PKD1L2 with BMI above or equal to 25 exhibited a significant increase in CRC risk (OR=2.29, 95% CI 1.29-4.05, P=.005). PKD1L2 CNV with BMI above or equal to 25 and age below 50 is associated with a remarkably increased risk of colorectal cancer (OR=5.24, 95% CI 2.36-11.64, P= 4.8x10-5). Moreover, we found that PKD1L2 variation in obese patients (BMI>=25) was associated with poor survival rate (P=.026). Our results suggest that the common PKD1L2 CNV is associated with CRC, and PKD1L2 CNV with high BMI and/or age below 50 exhibited a significant increased risk of CRC. In obese patients, PKD1L2 variation was associated with poor survival. This article is protected by copyright. All rights reserved.
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- 2016
183. STAT3 is a key molecule in the oncogenic behavior of diffuse intrinsic pontine glioma
- Author
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Kyung Hyun Kim, Jinju Park, Ji Yeoun Lee, Woochan Lee, Sangil Yun, Seung-Ki Kim, Saet Pyoul Kim, Kyu-Chang Wang, and Jong‑Il Kim
- Subjects
0301 basic medicine ,Cancer Research ,Cell ,Articles ,Biology ,Cell cycle ,medicine.disease_cause ,Neural stem cell ,Small hairpin RNA ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Viability assay ,Epithelial–mesenchymal transition ,Carcinogenesis ,Gliogenesis - Abstract
Diffuse intrinsic pontine glioma (DIPG) is one of the most lethal childhood brain tumors. This tumor is unique because it is detected exclusively in the ventral pons of patients aged between 6 and 7 years, which suggests a developmental nature of its formation. Signal transducer and activator of transcription 3 (STAT3) is a critical molecule for the differentiation of neural stem cells into astrocytes during neurodevelopment. Additionally, STAT3 is associated with oncogenesis and the epithelial-mesenchymal transition (EMT) in various types of tumor. In recent years, several studies have demonstrated the oncogenic role of STAT3 in high-grade gliomas. However, the role of STAT3 in DIPG at the cellular level remains unknown. To assess the possible association between gliogenesis and DIPG, the expression levels of various molecules participating in the differentiation of neural stem cells were compared between normal brain control tissues and DIPG tissues using open public data. All of the screened genes exhibited significantly increased expression in DIPG tissues compared with normal tissues. As STAT3 expression was the most increased, the effect of STAT3 inhibition in a DIPG cell line was assessed via STAT3 short hairpin (sh)RNA transfection and treatment with AG490, a STAT3 inhibitor. Changes in viability, apoptosis, EMT and radiation therapy efficiency were also evaluated. Downregulation of STAT3 resulted in decreased cyclin D1 expression and cell viability, migration and invasion. Additionally, treatment with STAT3 shRNA or AG490 suppressed the EMT phenotype. Finally, when radiation was administered in combination with STAT3 inhibition, the therapeutic efficiency, assessed by cell viability and DNA damage repair, was increased. The present results suggest that STAT3 is a potential therapeutic target in DIPG, especially when combined with radiation therapy.
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- 2019
184. Targeted next-generation DNA sequencing identifies Notch signaling pathway mutation as a predictor of radiation response
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Seock Ah Im, Min Jung Kim, Jong Il Kim, Tae-You Kim, Seung Hyuck Jeon, Eui Kyu Chie, Kyung Hun Lee, Hyun Seob Lee, and Yi Jun Kim
- Subjects
Adult ,Male ,Somatic cell ,medicine.medical_treatment ,Notch signaling pathway ,Radiogenomics ,Biology ,DNA sequencing ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Neoplasms ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Radiosensitivity ,Aged ,Radiological and Ultrasound Technology ,Receptors, Notch ,High-Throughput Nucleotide Sequencing ,Genomics ,Sequence Analysis, DNA ,Middle Aged ,Radiation therapy ,Treatment Outcome ,030220 oncology & carcinogenesis ,Mutation (genetic algorithm) ,Mutation ,Cancer research ,Female ,Radiation response ,Signal Transduction - Abstract
Purpose: Identifying the association between somatic mutations and the radiation response of tumor is essential for understanding the mechanisms and practicing personalized radiotherapy. The presen...
- Published
- 2019
185. Diagnostic Yield of Epilepsy Panel Testing in Patients With Seizure Onset Within the First Year of Life
- Author
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Se Song Jang, Soo Yeon Kim, Hunmin Kim, Hee Hwang, Jong Hee Chae, Ki Joong Kim, Jong-Il Kim, and Byung Chan Lim
- Subjects
0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,seizure ,First year of life ,Neonatal onset ,Germline ,lcsh:RC346-429 ,03 medical and health sciences ,Epilepsy ,Seizure onset ,0302 clinical medicine ,medicine ,In patient ,Copy-number variation ,lcsh:Neurology. Diseases of the nervous system ,Original Research ,target panel sequencing ,business.industry ,medicine.disease ,030104 developmental biology ,Neurology ,diagnostic yield ,genetic test ,Etiology ,epilepsy ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Purpose: We aimed to evaluate the diagnostic yield of epilepsy gene panel testing in epilepsy patients whose seizures began within the first year after birth. We included 112 patients with seizure onset before 12 months and no known etiology. Methods: Deep targeted sequencing with a custom-designed capture probe was performed to ensure the detection of germline or mosaic sequence variants and copy number variations (CNVs). Results: We identified pathogenic or likely pathogenic variants in 53 patients (47.3%, 53/112), including five with pathogenic CNVs. Two putative pathogenic mosaic variants in SCN8A and KCNQ2 were also detected and validated. Those with neonatal onset (61.5%, 16/26) or early infantile onset (50.0%, 29/58) showed higher diagnostic rates than those with late infantile onset (28.5%, 8/28). The diagnostic rate was similar between patients with a specific syndrome (51.9%, 27/52) and those with no recognizable syndrome (43.3%, 26/60). Conclusion: Epilepsy gene panel testing identified a genetic cause in nearly half of the infantile onset epilepsy patients. Since the phenotypic spectrum is expanding and characterizing it at seizure onset is difficult, this group should be prioritized for epilepsy gene panel testing.
- Published
- 2019
186. Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia
- Author
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Jong Il Kim, Woo-Young Sim, Dong Young Kim, Soo Jung Kwak, Arang Rhie, Ho Young Son, Seungbok Lee, Seong Jin Jo, Jeong-Sun Seo, Oh Sang Kwon, and Bark Lynn Lew
- Subjects
0301 basic medicine ,Oncology ,Male ,Heredity ,Biochemistry ,030207 dermatology & venereal diseases ,chemistry.chemical_compound ,0302 clinical medicine ,Mathematical and Statistical Techniques ,5-alpha Reductase Inhibitors ,Drug Metabolism ,Polymorphism (computer science) ,Medicine and Health Sciences ,Skin ,Multidisciplinary ,Statistics ,Middle Aged ,Exact test ,Genetic Mapping ,Physical Sciences ,Androgens ,Medicine ,Regression Analysis ,Anatomy ,Integumentary System ,Research Article ,Adult ,medicine.medical_specialty ,Science ,Single-nucleotide polymorphism ,Variant Genotypes ,Linear Regression Analysis ,Research and Analysis Methods ,Polymorphism, Single Nucleotide ,Molecular Genetics ,03 medical and health sciences ,Young Adult ,Hair Follicles ,Internal medicine ,medicine ,Genetics ,SNP ,Humans ,Pharmacokinetics ,Allele ,Statistical Methods ,Molecular Biology ,Alleles ,Pharmacology ,business.industry ,Case-control study ,Biology and Life Sciences ,Alopecia ,Dutasteride ,medicine.disease ,Hormones ,030104 developmental biology ,Hair loss ,chemistry ,Genetic Loci ,Case-Control Studies ,business ,Mathematics ,Hair - Abstract
Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic variants associated with response to dutasteride treatment for MPHL, a total of 42 men with moderate MPHL who had been treated with dutasteride for 6 months were genotyped and analysed by quantitative linear regression, case-control association tests, and Fisher’s exact test. The synonymous single nucleotide polymorphism (SNP) rs72623193 in DHRS9 was most significantly associated with response to dutasteride, followed by the non-synonymous SNP rs2241057 in CYP26B1. Additionally, variants in ESR1, SRD5A1, CYP19A1, and RXRG are suggested to be associated with response to dutasteride. Cumulative effect and interaction among these SNPs were presented in both additive and non-additive models.
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- 2019
187. A genome-wide by PM
- Author
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Hyun-Jin, Kim, Yong-Seok, Seo, Joohon, Sung, Jeesoo, Chae, Jae Moon, Yun, Hyuktae, Kwon, Belong, Cho, Jong-Il, Kim, and Jin-Ho, Park
- Subjects
Adult ,Male ,Air Pollutants ,Genotype ,Vital Capacity ,Environmental Exposure ,Middle Aged ,Cytoskeletal Proteins ,Interleukin 1 Receptor Antagonist Protein ,Asian People ,Air Pollution ,Republic of Korea ,Humans ,Particulate Matter ,Alleles ,Adaptor Proteins, Signal Transducing ,Genome-Wide Association Study ,Interleukin-1 - Abstract
Although several genome-wide interaction studies (GWIS) have been performed in specific European populations to understand the missing link between genetic and environmental factors for lung function, GWIS of Asian samples remain rare. Therefore, we performed a GWIS of exposure to air pollution to identify loci for lung function in Korean adult men. A total of 1826 adult men recruited from two health check-up centers were included in the analysis and the annual mean concentrations of ambient particulate matter with an aerodynamic diameter ≤10 μm (PM
- Published
- 2019
188. Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy
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Ji Seon Yoon, Sungjoo Tommy Hwang, Bo Mi Kang, Woochan Lee, Jin Yong Kim, Oh Sang Kwon, Kyu Han Kim, Jong Il Kim, Minji Park, Jungyoon Ohn, and Sookyung Kim
- Subjects
0301 basic medicine ,General Physics and Astronomy ,Apoptosis ,02 engineering and technology ,Mice, SCID ,p38 Mitogen-Activated Protein Kinases ,Mice ,Phosphatidylinositol 3-Kinases ,Regeneration in humans ,lcsh:Science ,Mitotic catastrophe ,Cells, Cultured ,Adult stem cells ,Multidisciplinary ,integumentary system ,Stem Cells ,Middle Aged ,021001 nanoscience & nanotechnology ,Cell biology ,Heterografts ,Female ,Stem cell ,0210 nano-technology ,Hair Follicle ,Adult stem cell ,medicine.drug ,Adult ,Alkylating Agents ,DNA damage ,Science ,Transplantation, Heterologous ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,medicine ,Regeneration ,Chemotherapy ,Animals ,Humans ,Busulfan ,Cyclophosphamide ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,General Chemistry ,Transplantation ,030104 developmental biology ,lcsh:Q ,Tumor Suppressor Protein p53 ,Proto-Oncogene Proteins c-akt ,DNA Damage - Abstract
The maintenance of genetic integrity is critical for stem cells to ensure homeostasis and regeneration. Little is known about how adult stem cells respond to irreversible DNA damage, resulting in loss of regeneration in humans. Here, we establish a permanent regeneration loss model using cycling human hair follicles treated with alkylating agents: busulfan followed by cyclophosphamide. We uncover the underlying mechanisms by which hair follicle stem cells (HFSCs) lose their pool. In contrast to immediate destructive changes in rapidly proliferating hair matrix cells, quiescent HFSCs show unexpected massive proliferation after busulfan and then undergo large-scale apoptosis following cyclophosphamide. HFSC proliferation is activated through PI3K/Akt pathway, and depletion is driven by p53/p38-induced cell death. RNA-seq analysis shows that HFSCs experience mitotic catastrophe with G2/M checkpoint activation. Our findings indicate that priming mobilization causes stem cells to lose their resistance to DNA damage, resulting in permanent loss of regeneration after alkylating chemotherapy., Hair follicles (HFs) are sensitive to chemotherapy but recover from quiescent HF stem cells, although sometimes chemotherapy results in permanent loss. Here, Kim et al. establish a model of permanent chemotherapy-induced alopecia to uncover the underlying mechanisms depleting human HF stem cells.
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- 2019
189. A newly developed capture-based sequencing panel for genomic assay of lung cancer
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Jaeyong Choi, Yoohwa Hwang, Yoon Kyung Jeon, Soojin Cha, Jihui Yun, Miso Kim, Dong Wan Kim, Jeesoo Chae, Sun Wha Im, Jong Il Kim, Tae Min Kim, Se Song Jang, Nak Jung Kwon, and Young Tae Kim
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0106 biological sciences ,0301 basic medicine ,Lung Neoplasms ,DNA Copy Number Variations ,Computational biology ,Biology ,01 natural sciences ,Biochemistry ,Polymorphism, Single Nucleotide ,Sensitivity and Specificity ,DNA sequencing ,03 medical and health sciences ,INDEL Mutation ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Copy-number variation ,International HapMap Project ,Precision Medicine ,Lung cancer ,Molecular Biology ,Allele frequency ,Genetic testing ,Massive parallel sequencing ,Polymorphism, Genetic ,medicine.diagnostic_test ,Cancer ,High-Throughput Nucleotide Sequencing ,Sequence Analysis, DNA ,medicine.disease ,Data Accuracy ,Neoplasm Proteins ,030104 developmental biology ,Genomic Structural Variation ,Mutation ,010606 plant biology & botany ,Genes, Neoplasm - Abstract
The increase in genetic alterations targeted by specific chemotherapy in lung cancer has led to the need for universal use of more comprehensive genetic testing, which has highlighted the development of a lung cancer diagnostic panel using next-generation sequencing. We developed a hybridization capture-based massively parallel sequencing assay named Friendly, Integrated, Research-based, Smart and Trustworthy (FIRST)-lung cancer panel (LCP), and evaluated its performance. FIRST-LCP comprises 64 lung cancer-related genes to test for various kinds of genetic alterations including single nucleotide variations (SNVs), insertions and deletions (indels), copy number variations (CNVs), and structural variations. To assess the performance of FIRST-LCP, we compiled test sets using HapMap samples or tumor cell lines with disclosed genetic information, and also tested our clinical lung cancer samples whose genetic alterations were known by conventional methods. FIRST-LCP accomplished high sensitivity (99.4%) and specificity (100%) of the detection of SNVs. High precision was also achieved, with intra- or inter-run concordance rate of 0.99, respectively. FIRST-LCP detected indels and CNVs close to the expected allele frequency and magnitude, respectively. Tests with samples from lung cancer patients also identified all SNVs, indels and fusions. Based on the current state of the art, continuous application of the panel design and analysis pipeline following up-to-date knowledge could ensure precision medicine for lung cancer patients.
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- 2019
190. Clinical Application of Next-Generation Sequencing-Based Panel to
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Changhee, Park, Miso, Kim, Min Jung, Kim, Hyeongmin, Kim, Chan-Young, Ock, Bhumsuk, Keam, Tae Min, Kim, Dong-Wan, Kim, Jong-Il, Kim, and Dae Seog, Heo
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Adult ,Aged, 80 and over ,Male ,Proto-Oncogene Proteins B-raf ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Prognosis ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Antineoplastic Agents, Immunological ,Mutation ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Humans ,Female ,Melanoma ,Aged ,Follow-Up Studies - Abstract
Molecular profiling with next-generation sequencing (NGS) has been applied in multiple solid cancers to discover potential therapeutic targets. Here, we describe the results of a clinical NGS panel in patients with advanced melanoma. Thirty-six tumor tissues from patients with
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- 2019
191. Whole-genome reference panel of 1,781 Northeast Asians improves imputation accuracy of rare and low-frequency variants
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Jong Il Kim, Stephan C. Schuster, Kwok Wai Lo, Belong Cho, Seong Keun Yoo, Jeong-Sun Seo, Chang Uk Kim, Namcheol Kim, Hie Lim Kim, Jong Yeon Shin, Joshua SungWoo Yang, Changhoon Kim, Sungjae Kim, and Fumihiko Matsuda
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Genotype imputation ,Geography ,Statistics ,Sequencing data ,Haplotype ,Genotype ,Reference database ,1000 Genomes Project ,Genome ,Imputation (genetics) - Abstract
Genotype imputation using the reference panel is a cost-effective strategy to fill millions of missing genotypes for the purpose of various genetic analyses. Here, we present the Northeast Asian Reference Database (NARD), including whole-genome sequencing data of 1,781 individuals from Korea, Mongolia, Japan, China, and Hong Kong. NARD provides the genetic diversities of Korean (n=850) and Mongolian (n=386) ancestries that were not present in the 1000 Genomes Project Phase 3 (1KGP3). We combined and re-phased the genotypes from NARD and 1KGP3 to construct a union set of haplotypes. This approach established a robust imputation reference panel for the Northeast Asian populations, which yields the greatest imputation accuracy of rare and low-frequency variants compared with the existing panels. Also, we illustrate that NARD can potentially improve disease variant discovery by reducing pathogenic candidates. Overall, this study provides a decent reference panel for the genetic studies in Northeast Asia.
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- 2019
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192. Unstable genome and transcriptome dynamics during tumor metastasis contribute to therapeutic heterogeneity in colorectal cancers
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Boram Choi, Charles Lee, Hansoo Park, Deukchae Na, Jeesoo Chae, Jeffrey H. Chuang, Wonyoung Kang, Seoyeon Min, Jinjoo Kang, Ji Eun Lee, Won-Suk Lee, Chang Ohk Sung, Ahra Lee, Jong Il Kim, and Sung Yup Cho
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0301 basic medicine ,Cancer Research ,Colorectal cancer ,Antineoplastic Agents ,Apoptosis ,Mice, SCID ,Biology ,medicine.disease_cause ,Article ,Metastasis ,Transcriptome ,03 medical and health sciences ,Genetic Heterogeneity ,Mice ,0302 clinical medicine ,Mice, Inbred NOD ,Exome Sequencing ,medicine ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Animals ,Humans ,Neoplasm Metastasis ,Exome sequencing ,Phylogeny ,Epigenomics ,Cell Proliferation ,Mutation ,Genetic heterogeneity ,Genome, Human ,High-Throughput Nucleotide Sequencing ,medicine.disease ,Prognosis ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,DNA methylation ,Cancer research ,Female ,Colorectal Neoplasms - Abstract
Purpose: Genomic and transcriptomic alterations during metastasis are considered to affect clinical outcome of colorectal cancers, but detailed clinical implications of metastatic alterations are not fully uncovered. We aimed to investigate the effect of metastatic evolution on in vivo treatment outcome, and identify genomic and transcriptomic alterations associated with drug responsiveness. Experimental Design: We developed and analyzed patient-derived xenograft (PDX) models from 35 patients with colorectal cancer including 5 patients with multiple organ metastases (MOMs). We performed whole-exome, DNA methylation, and RNA sequencing for patient and PDX tumors. With samples from patients with MOMs, we conducted phylogenetic and subclonal analysis and in vivo drug efficacy test on the corresponding PDX models. Results: Phylogenetic analysis using mutation, expression, and DNA methylation data in patients with MOMs showed that mutational alterations were closely connected with transcriptomic and epigenomic changes during the tumor evolution. Subclonal analysis revealed that initial primary tumors with larger number of subclones exhibited more dynamic changes in subclonal architecture according to metastasis, and loco-regional and distant metastases occurred in a parallel or independent fashion. The PDX models from MOMs demonstrated therapeutic heterogeneity for targeted treatment, due to subclonal acquisition of additional mutations or transcriptomic activation of bypass signaling pathway during tumor evolution. Conclusions: This study demonstrated in vivo therapeutic heterogeneity of colorectal cancers using PDX models, and suggests that acquired subclonal alterations in mutations or gene expression profiles during tumor metastatic processes can be associated with the development of drug resistance and therapeutic heterogeneity of colorectal cancers.
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- 2019
193. Iron Content in Relationship with Alloying Elements and Corrosion Behaviour of Mg3Al Alloys
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Young Min Kim, Ha Ngoc Nguyen, Bong Sun You, and Jong Il Kim
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Materials science ,Magnesium ,Metallurgy ,technology, industry, and agriculture ,chemistry.chemical_element ,Yttrium ,Manganese ,Calcium ,equipment and supplies ,Corrosion ,Matrix (chemical analysis) ,chemistry ,Iron content ,Magnesium alloy - Abstract
In the present study, the effect of various alloying elements on controlling of iron content in magnesium alloys was investigated. A number of alloying elements including manganese, calcium, and yttrium were added separately and simultaneously to the melt then the iron content was determined. The effect of elements on iron removing was evaluated and compared. The results were interesting since it has changed the idea of considering manganese as the best to remove iron from the melt. Other elements would be a better candidate to improve the corrosion resistance of magnesium alloys, especially yttrium due to its double effect on iron removing and forming of a protective film to protect the matrix. This study would contribute effectively to a design of high-performance magnesium alloys in the future.
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- 2019
194. MOESM2 of Comparative genomics of Mycoplasma pneumoniae isolated from children with pneumonia: South Korea, 2010â€'2016
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Lee, Joon, Moon-Woo Seong, Dongjin Shin, Jong-Il Kim, Han, Mi, Youbin Yeon, Cho, Sung, Park, Sung, and Choi, Eun
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Additional file 2: Phylogenetic tree based on whole genome alignment of the 30 sequenced strains.
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- 2019
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195. MOESM1 of NARD: whole-genome reference panel of 1779 Northeast Asians improves imputation accuracy of rare and low-frequency variants
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Seong-Keun Yoo, Kim, Chang-Uk, Kim, Hie, Sungjae Kim, Jong-Yeon Shin, Namcheol Kim, Yang, Joshua, Kwok-Wai Lo, Belong Cho, Matsuda, Fumihiko, Schuster, Stephan, Changhoon Kim, Jong-Il Kim, and Jeong-Sun Seo
- Abstract
Additional file 1: Figure S1. Geographic map of the study area in the NARD. Figure S2. Correlation between the sequencing depth and number of variants. Figure S3. Transition to transversion ratio of the populations in the NARD. Figure S4. Heterozygous to homozygous ratio of the global populations. Figure S5. Number of loss-of-function variants. Figure S6. Hardy-Weinberg Equilibrium test of variants in the NARD. Figure S7. Novel variant statistics. Figure S8. Differential genetic composition of the two MNG groups. Figure S9. Imputation performance evaluation of FRA individuals. Figure S10. Imputation performance evaluation of CHN and JPN individuals. Figure S11. Length distribution of shared IBD tracts between the two individuals in each population. Figure S12. The flow chart of the pipeline consisting of four major steps for NARD imputation server. Figure S13. The cross-validation error inferred by ADMIXTURE algorithm.
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- 2019
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196. Dissecting the phenotypic and genetic spectrum of early childhood-onset generalized epilepsies
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Ki Joong Kim, Jong Hee Chae, Byung Chan Lim, Hunmin Kim, Hee Hwang, Jong Il Kim, Jieun Choi, Se Song Jang, and Soo Yeon Kim
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Male ,Pediatrics ,medicine.medical_specialty ,GABA Plasma Membrane Transport Proteins ,Epilepsies, Myoclonic ,SYNGAP1 ,Seizures, Febrile ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Febrile seizure ,medicine ,Humans ,Genetic Testing ,Generalized epilepsy ,Age of Onset ,Exome sequencing ,Genetic testing ,Glucose Transporter Type 1 ,medicine.diagnostic_test ,business.industry ,Seizure types ,Infant ,Electroencephalography ,General Medicine ,medicine.disease ,Neurology ,Epilepsy, Absence ,Child, Preschool ,Epilepsy syndromes ,Epilepsy, Generalized ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Purpose Although the genetic and clinical aspects of epilepsy with myoclonic-atonic seizures (MAE) and early onset absence epilepsy (EOAE) have been investigated thoroughly, other early childhood-onset generalized epilepsies that share clinical features with MAE and EOAE have not been characterized. In this study, we aimed to delineate the genetic and phenotypic spectrum of early childhood-onset generalized epilepsies, including MAE and EOAE. Methods We recruited 61 patients diagnosed with MAE, EOAE, genetic epilepsy with febrile seizure plus (GEFS+) and unclassified generalized epilepsies that shared seizure onset age and seizure types. Genetic causes were investigated through targeted gene panel testing, whole exome sequencing, chromosomal microarray, and single-gene Sanger sequencing. Results We classified 11 patients with MAE, 20 with EOAE, 9 with GEFS + spectrum. Epilepsy syndrome was not specified in the remaining 21 patients. The clinical features were comparable across groups. Nevertheless, patients with EOAE tended to show better developmental and seizure outcomes. A total of 23 pathogenic sequences and copy number variants from 12 genes were identified (23/61, 37.7%). Genetic etiologies were confirmed in 36.4% (4/11) of the MAE group, 45% (9/20) of the EOAE group, 22.2% (2/9) of the GEFS + spectrum, and 38.1% (8/21) of the unclassified group. The most frequently identified genes with pathogenic variants were SLC6A1 (7 patients), SLC2A1 (4 patients), and SYNGAP1 (4 patients). Conclusion Early childhood-onset generalized epilepsy appeared to be characterized by an overlapping genetic and phenotypic spectrum. SLC6A1 and SLC2A1 appeared to be important genetic causes of early childhood-onset generalized epilepsy.
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- 2018
197. Identifying Pathogenic Variants of Monogenic Diabetes Using Targeted Panel Sequencing in an East Asian Population
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Choong Ho Shin, Jong Il Kim, Young Ah Lee, Sung Hee Choi, Seung Shin Park, Se Song Jang, Sunghoon Kim, Young Min Cho, Chang Ho Ahn, Jee Cheol Bae, Soo Heon Kwak, Jae Hyun Kim, Jong Cheol Won, Kyong Soo Park, Jung Hee Kim, Hye Seung Jung, Jong Hee Chae, and Hak Chul Jang
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Population ,Biochemistry ,Maturity onset diabetes of the young ,ABCC8 ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Medicine ,education ,Genetic testing ,Genetics ,education.field_of_study ,biology ,medicine.diagnostic_test ,business.industry ,Biochemistry (medical) ,medicine.disease ,HNF1A ,biology.protein ,Medical genetics ,Age of onset ,business - Abstract
Purpose Monogenic diabetes is a specific type of diabetes in which precision medicine could be applied. In this study, we used targeted panel sequencing to investigate pathogenic variants in Korean patients with clinically suspected monogenic diabetes. Methods The eligibility criteria for inclusion were patients with nontype 1 diabetes with age at onset ≤30 years and body mass index (BMI) ≤30 kg/m2. Among the 2090 patients with nontype 1 diabetes, 109 had suspected monogenic diabetes and underwent genetic testing. We analyzed 30 monogenic diabetes genes using targeted panel sequencing. The pathogenicity of the genetic variants was evaluated according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Results Among the 109 patients with suspected monogenic diabetes, 23 patients (21.1%) harbored pathogenic/likely pathogenic variants. A total of 14 pathogenic/likely pathogenic variants of common maturity-onset diabetes of the young (MODY) genes were identified in GCK, HNF1A, HNF4A, and HNF1B. Other pathogenic/likely pathogenic variants were identified in WFS1, INS, ABCC8, and FOXP3. The mitochondrial DNA 3243A>G variant was identified in five participants. Patients with pathogenic/likely pathogenic variants had a significantly higher MODY probability, a lower BMI, and a lower C-peptide level than those without pathogenic/likely pathogenic variants (P = 0.007, P = 0.001, and P = 0.012, respectively). Conclusions Using targeted panel sequencing followed by pathogenicity evaluation, we were able to make molecular genetic diagnoses for 23 patients (21.1%) with suspected monogenic diabetes. Lower BMI, higher MODY probability, and lower C-peptide level were characteristics of these participants.
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- 2018
198. Author Correction: Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts
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Michael Lloyd, R. Jay Mashl, Yvonne A. Evrard, Jeffrey A. Moscow, Jong Il Kim, Alana L. Welm, Michael A. Davies, Carol J. Bult, Jayamanna Wickramasinghe, Rania El Botty, Dennis A. Dean, Jessica Giordano, Anuj Srivastava, Sandra D. Scherer, Jacqueline Rosains, Christian Frech, Elisabetta Marangoni, Jeffrey H. Chuang, Ryan Jeon, Shunqiang Li, Matthew H. Bailey, Yun-Suhk Suh, Elodie Modave, Yuanxin Xi, Enzo Medico, Li Ding, Livio Trusolino, Adam Lafferty, Vito W. Rebecca, Han-Kwang Yang, Jing Wang, Annette T. Byrne, Xing Yi Woo, Alice C. O’Farrell, Claudio Isella, Li Chen, Brandi N. Davis-Dusenbery, James H. Doroshow, Sherri R. Davies, Diether Lambrechts, Jos Jonkers, Bingliang Fang, Charles Lee, Roebi de Bruijn, Violeta Serra, Jack A. Roth, Rajesh Patidar, Funda Meric-Bernstam, Petra ter Brugge, Andrew V. Kossenkov, Hyun-Soo Kim, Andrea Bertotti, Emilio Cortes-Sanchez, Chieh-Hsiang Yang, Ramaswamy Govindan, Francesco Galimi, Jelena Randjelovic, Zi-Ming Zhao, Bryan E. Welm, Hua Sun, Meenhard Herlyn, and Michael T. Lewis
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Oncology ,medicine.medical_specialty ,DNA Copy Number Variations ,MEDLINE ,Biology ,Polymorphism, Single Nucleotide ,Mice ,Text mining ,Internal medicine ,Databases, Genetic ,Exome Sequencing ,Genetics ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,Author Correction ,Cancer ,business.industry ,Published Erratum ,medicine.disease ,Xenograft Model Antitumor Assays ,Computational biology and bioinformatics ,Gene Expression Regulation, Neoplastic ,business - Abstract
Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.
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- 2021
199. Treatment strategy for papillary renal cell carcinoma type 2: a case series of seven patients treated based on next generation sequencing data
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Semin Lee, Jong Il Kim, Kyung Chul Moon, Ji-Yeon Kim, Hyoung-oh Jeong, Se-Hoon Lee, Cheol Kwak, Bhumsuk Keam, Seunghoon Kim, Jinho Jang, and Dae Seog Heo
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Mutation ,business.industry ,medicine.medical_treatment ,General Medicine ,medicine.disease_cause ,Germline ,Papillary renal cell carcinoma type 2 ,Targeted therapy ,Axitinib ,Pazopanib ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Germline mutation ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Original Article ,business ,Exome ,medicine.drug - Abstract
Background Papillary renal cell carcinoma type 2 (PRCC2) is refractory to systemic treatment and has a dismal prognosis. Previous studies showed that genetic alterations in PRCC2 were heterogeneous regardless of germline or somatic mutations. In this study, we aimed to perform precision treatment of PRCC2 based on genetic information. Methods We performed exome and genome sequencing of tumor tissues and matched normal samples. Based on sequencing data, we treated patients with metastatic PRCC2 using precision oncology. Results Four patients underwent curative surgery of PRCC2 and three patients had metastatic PRCC2. All PRCC2 heterogeneously harbored own driver mutations. Two out of the three patients with metastatic disease had fumarate hydratase (FH) germline mutations. One patient with a germline FH mutation was diagnosed with hereditary leiomyomatosis RCC. He was treated with bevacizumab and erlotinib combination and showed a durable response. The other metastatic PRCC2 patient harboring a germline FH mutation had an additional somatic FH mutation and was durably controlled with pazopanib. Other metastatic PRCC2 patient with somatic PBRM1 and SETD2 mutations had over 5 years of overall survival with axitinib treatment. Conclusions We performed precision systemic treatment based on genetic information. Genome sequencing could help identify candidates for targeted therapy in PRCC2, a genetically heterogeneous disease.
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- 2020
200. Genome-Wide Association Study of Bone Mineral Density in Korean Men
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Soon Hang Lee, S. Im, Jin Ho Park, You Seon Nam, Jin Hee Kim, Jae Moon Yun, Ho Young Son, San Deok Yang, Kwang Ho Oh, Ye Seul Bae, Mi So Kang, Belong Cho, Joohon Sung, and Jong Il Kim
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0301 basic medicine ,musculoskeletal diseases ,medicine.medical_specialty ,Bone density ,Koreans ,lcsh:QH426-470 ,Osteoporosis ,men ,Health Informatics ,Single-nucleotide polymorphism ,Locus (genetics) ,Genome-wide association study ,Biology ,03 medical and health sciences ,single nucleotide polymorphisms ,Internal medicine ,Genetics ,medicine ,Femur ,Ecology, Evolution, Behavior and Systematics ,Bone mineral ,genome-wide association study ,bone density ,medicine.disease ,musculoskeletal system ,lcsh:Genetics ,030104 developmental biology ,Endocrinology ,Original Article ,Body mass index - 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.
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- 2016
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