• Clinical and Experimental Pediatrics
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• v.57 no.1
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• pp.46-49
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• 2014

CHARGE syndrome has been estimated to occur in 1:10,000 births worldwide and shows various clinical manifestations. It is a genetic disorder characterized by a specific and a recognizable pattern of anomalies. The major clinical features are ocular coloboma, heart malformations, atresia of the choanae, growth retardation, genital hypoplasia, and ear abnormalities. The chromodomain helicase DNA-binding protein 7 (CHD7) gene, located on chromosome 8q12.1, causes CHARGE syndrome. The CHD7 protein is an adenosine triphosphate (ATP)-dependent chromatin remodeling protein. A total of 67% of patients clinically diagnosed with CHARGE syndrome have CHD7 mutations. Five hundred twenty-eight pathogenic and unique CHD7 alterations have been identified so far. We describe a patient with a CHARGE syndrome diagnosis who carried a novel de novo mutation, a c.3896T>C (p. leu1299Pro) missense mutation, in the CHD7 gene. This finding will provide more information for genetic counseling and expand our understanding of the pathogenesis and development of CHARGE syndrome.

• Proceedings of the Zoological Society Korea Conference
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• 1994.10a
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• pp.60-60
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• 1994

No Abstract, See Full Text

• Animal cells and systems
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• v.3 no.3
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• pp.331-336
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• 1999

p56$^{Ick}$, a cytoplasmic protein tyrosine kinase of the src family, is non-covalently associated with the cell surface coreceptors CD4 and CD8, which are expressed on thymocytes and mature T cells. The coreceptor protein plays an important role during the differentiation of thymocytes and the activation of T cells. DNA constructs were designed to study the roles of CD4 and CD8 during the differentiation of thymocytes. One is a chimeric cDNA which consists of coding regions for the extracellular domain of CD8a and the transmembrane and cytoplasmic domain of CD4. The other is the same chimeric cDNA but with a point mutation converting Cys to Ala in the Ick-binding site to disrupt the association. We confirmed that the CD8a/CD4 chimeric molecule bound to Ick more efficiently than the wild type CD8a protein. However, the chimeric protein with the Cys$leftrightarro$Ala mutation did not associate with Ick. The results suggest a possibility that the CD8a/CD4 chimeric protein may behave like a CD4 protein in associating with Ick and that it may deliver a signal inside the cell in a similar manner, Analysing effects of the mutant CD8a/CD4 chimeric protein expression in developing thymocytes will elucidate the role of Ick during the determination of CD4/CD8 cell lineages.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.151-161
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• 2001

Background: Inactivation in p53 tumor suppressor gene through a point mutation and deletion is one of the most frequent genetic changes found in human cancer, with 50% of an incidence. This high rate of mutation mostly suggests that the gene plays a central role in the development of cancer and the mutations detected so far were found in exons 5 to 8. Mutation of p53 locus produced accumulation of abnormal p53 protein, and negative regulation of cell proliferation and transcriptional activation as a suppressor of transformation were lost. In addition, inhibition of its normal cellular function of wild-type by mutant is an important step in tumorigenesis. Method: 4 colon cancer cell lines (SNU C1, C2A, C4, C5) were examined for mutation in exons 5 to 8 of the p53 tumor suppressor gene by PCR-SSCP analysis and expression pattern by western blotting and immunoprecipitation. p53-mediated transactivation ability were examined by CAT assay and base substitution of p53 in SNU C2A cell were detected by DNA sequencing. Results: 1) SNU C2A cell and SNU C5 cell were detected mobility shifts each in exon 5 and exon 7 of p53 gene by the PCR-SSCP method, implicating being of p53 mutation. 2) 3 colon cancer cell lines (SNU C1, SNU C2A, SNU C5) expressed wild type and mutant type p53 protein. 3) In northern blot experiment, SNU C2A and SNU C5 cell expressed high level of p53 mRNA. 4) Results of p53-mediated transactivation in colon cancer cell lines by CAT assay represented only SNU C2A cell has transcriptional activity. 5) DNA sequencing in SNU C2A cell showed missense mutation in codon 179 of one allele, histidine to arginine and wild type p53 in the other allele. Conclusion: Colon cancer cell lines showed correlation with mutation in p53 gene and accumulation of abnormal p53 protein. Colon cancer cell SNU C2A retained p53-mediated transactivation as heterozygous p53 with one mutant allele in 179 codon and the other wild-type allele.

• Food Science of Animal Resources
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• v.38 no.4
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• pp.711-717
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• 2018

Myogenic factor 5 (MYF5) plays an important role in regulating skeletal muscle fiber characteristics, consequently affecting meat production and quality. We identified a novel p.A41P mutation in exon1 of the porcine MYF5 gene by direct sequencing. The mutation was predicted to be destabilizing in protein structure based on the resultant amino acid substitution. We estimated the significant substitution effect of p.A41P on the energy stabilization of Myf5 protein structure. Then, we demonstrated that the mutation in Yorkshire population significantly affected muscle fiber type I composition (p<0.05), loin-eye area of lean meat content (p<0.05) and filter-fluid uptake of meat quality (p<0.01). Furthermore, dominant effects significantly influenced total muscle fiber number (p<0.05). This study suggests that the novel p.A41P mutation in porcine MYF5 may be a valuable genetic marker to affect the muscle fiber characteristics and consequently improve meat production quality and quantity.

• Nutritional Sciences
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• v.5 no.1
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• pp.13-19
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• 2002

A mutation in the promoter region of uncoupling protein 3 (UCF3), specifically the -55C longrightarrow T transition, may influence an individual's energy metabolism and body weight. The objective of this study was to investigate the effect of a weight reduction program on endocrine functions and body fat distribution, related to UCP3 promoter genotype. Ninety overweight pre-menopausal female subjects participated in the weight reduction program at Yonsei University Hospital, and were placed on a calorie-restricted diet (300 kcal less than their daily requirements) for 12 weeks. After 12 weeks, all subjects on the program lost approximately 5% of their initial body weights and had lower Body Mass Index (BMI) values. Among the 90 women, 56 had a normal (without mutation) UCP3 genotype, while 34 women had mutations in the promoter region of UCP3. Despite similar weight reductions in both groups, a significantly higher decrease in abdominal adipose tissue was observed in the normal UCP3 genotype group, compared to the group with mutations. In particular, there was a significant reduction of fat at the lumbar 1 (Ll) level in the without-mutation group. Serum levels of total cholesterol, apolipoprotein Al were significantly decreased in the without-mutation group, by 4.4% and 5.7% respectively. Serum levels of hormones were not significantly changed in both groups artier the intervention. However, in the group without the mutations, the leptin level significantly reduced by 23.4% (p<0.001). Serum free fatty acid (FFA) concentration was significantly increased in the group with mutation following the weight reduction program. On the other hand, FFA responses were shown similar increases in both groups. In conclusion, although no difference was found in the magnitude of weight reduction in both groups, there were significant differences in body fat distribution and in endocrine function between the groups.

• Genomics & Informatics
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• v.21 no.3
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• pp.32.1-32.11
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• 2023

Resistance to anti-tuberculosis drugs, especially ethambutol (EMB), has been widely reported worldwide. EMB resistance is caused by mutations in the embB gene, which encodes the arabinosyl transferase enzyme. This study aimed to detect mutations in the embB gene of Mycobacterium tuberculosis from Papua and to evaluate their impact on the effectiveness of EMB. We analyzed 20 samples of M. tuberculosis culture that had undergone whole-genome sequencing, of which 19 samples were of sufficient quality for further bioinformatics analysis. Mutation analysis was performed using TBProfiler, which identified M306L, M306V, D1024N, and E378A mutations. In sample TB035, the M306L mutation was present along with E378A. The binding affinity of EMB to arabinosyl transferase was calculated using AutoDock Vina. The molecular docking results revealed that all mutants demonstrated an increased binding affinity to EMB compared to the native protein (-0.948 kcal/mol). The presence of the M306L mutation, when coexisting with E378A, resulted in a slight increase in binding affinity compared to the M306L mutation alone. The molecular dynamics simulation results indicated that the M306L, M306L + E378A, M306V, and E378A mutants decreased protein stability. Conversely, the D1024N mutant exhibited stability comparable to the native protein. In conclusion, this study suggests that the M306L, M306L + E378A, M306V, and E378A mutations may contribute to EMB resistance, while the D1024N mutation may be consistent with continued susceptibility to EMB.

• BMB Reports
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• v.43 no.10
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• pp.704-709
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• 2010

The Swedish mutation (K595N/M596L) of amyloid precursor protein (APP-swe) has been known to increase abnormal cleavage of cellular APP by Beta-secretase (BACE), which causes tau protein hyperphosphorylation and early-onset Alzheimer's disease (AD). Here, we analyzed the effect of APP-swe in global gene expression using deep transcriptome sequencing technique. We found 283 genes were down-regulated and 348 genes were up-regulated in APP-swe expressing H4-swe cells compared to H4 wild-type cells from a total of approximately 74 million reads of 38 base pairs from each transcriptome. Two independent mechanisms such as kinase and phosphatase signaling cascades leading hyperphosphorylation of tau protein were regulated by the expression of APP-swe. Expressions of catalytic subunit as well as several regulatory subunits of protein phosphatases 2A were decreased. In contrast, expressions of tau-phosphorylating glycogen synthase kinase $3\beta$(GSK-3$\beta$), cyclin dependent kinase 5 (CDK5), and cAMP-dependent protein kinase A (PKA) catalytic subunit were increased. Moreover, the expression of AD-related Aquaporin 1 and presenilin 2 expression was regulated by APP-swe. Taken together, we propose that the expression of APP-swe modulates global gene expression directed to AD pathogenesis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.10a
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• pp.9-15
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• 1995

When quiescent cells ate stimulated to enter the cell cycle, the thymidine kinase(TK) gene is transcriptionally activated at the border of Gl and 5. In this report we show that the human TK promoter contains multiple protein-binding sites. By site-directed mutagenesis, we identified a protein-binding site on the human TK promoter requited for conferring Gl-S-regulated transcription to a heterologous promoter and dissociated it functionally from an adjacent protein-binding domain containing an inverted CCAAT motif requited for high basal level expression. Substitution-mutation of this site results in constitutive expression of the neo reporter gene in serum-stimulated fibroblasts, as well as in cells arrested in mid-Gl by a temperature-sensitive mutation. The regulatory domains for the human TK promoter exhibit interesting symmetrical features, including a set of CCAAT motifs and sites similar to the novel Yi protein-binding site recently discovered in the mouse TK promoter. Thus, components of the hTK complex is important for hTK gene regulation.

• BMB Reports
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• v.50 no.1
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• pp.37-42
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• 2017

The tubby protein (Tub), a putative transcription factor, plays important roles in the maintenance and function of neuronal cells. A splicing defect-causing mutation in the 3'-end of the tubby gene, which is predicted to disrupt the carboxy-terminal region of the Tub protein, causes maturity-onset obesity, blindness, and deafness in mice. Although this pathological Tub mutation leads to a loss of function, the precise mechanism has not yet been investigated. Here, we found that the mutant Tub proteins were mostly localized to puncta found in the perinuclear region and that the C-terminus was important for its solubility. Immunocytochemical analysis revealed that puncta of mutant Tub co-localized with the aggresome. Moreover, whereas wild-type Tub was translocated to the nucleus by extracellular signaling, the mutant forms failed to undergo such translocation. Taken together, our results suggest that the malfunctions of the Tub mutant are caused by its misfolding and subsequent localization to aggresomes.