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Angiotensin Converting Enzyme Gene Polymorphism in Alport Syndrome (알포트증후군 환자에서 안지오텐신전환효소 유전자 다형성의 의의)

  • Kim Ji-Hong;Lee Jae-Seung;Kim Pyung-Kil
    • Childhood Kidney Diseases
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    • v.8 no.1
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    • pp.18-25
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    • 2004
  • Purpose : Alport syndrome is clinically characterized by hereditary progressive nephritis causing ESRD with irregular thickening of the GBM and sensory neural hearing loss. The mutations of type IV collagen gene(COL4A5) located on the long arm of X chromosome is considered responsible for most of the structural abnormalities in the GBM of Alport patients. Since no definite clinical prognostic predictor has been reported in the disease yet, we designed this study to evaluate the significance of genetic polymorphism of the angiotensin converting enzyme in children with Alport syndrome as a prognostic factor for disease progression. Methods : ACE I/D genotype were examined by PCR amplification of the genomic DNA in 12 patients with Alport syndrome and 12 of their family members. Alport patients were divided into two groups; the conservative group, those who had preserved renal function for more than 10 years of age, the early CRF group, those who had progressed to CRF within 10 years of age. Results : The mean age of onset was $3.45{\pm}2.4$ years in the conservative group, $4.4{\pm}1.2$ years in the early CRF group. Sex ratios were 5:3 and 2:1 in each group. Among 12 cases of patients, 4 cases were in early CRF group and their mean duration of onset to CRF was 4.5 yews(8.9 years of age). Eight patients(67%) were in the conservative group and they had normal renal function for more than 10 years of age(mean duration of renal preservation was 10.6 years). The incidence of II type ACE gene were in 25.0%(3 cases), ID type in 41.7%(5 cases), DD type in 33.3%(4 cases). There was no significant difference between Alport patient and normal control(II type 44.3%, ID type 40.9%, DD type 14.8%). The incidence of DD type of early CRF group were higher than that of the conservative group(75% vs 12.5%)(p<0.05). There was no difference in ACE gene polymorphism between normal Alport family members and control group. Conclusion : Even though there was no significant difference of ACE polymorphism between Alport patients and the normal control group, the incidence of DD type is significantly increased in early CRF group which means DD type of ACE polymorphism has a possibility of being a predictor for early progression to CRF in Alport patients.

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Linkage Disequilibrium and Gene Expression Analyses of IGF2 Gene in Korean Native Pigs (재래돼지를 이용한 IGF2 유전자의 연관불균형과 유전자발현양상에 대한 분석)

  • Li, Song-Lan;Li, Xiaoping;Choi, Bong-Hwan;Lee, Cheol-Koo;Cho, Byung-Wook;Kim, Jong-Joo;Kim, Kwan-Suk
    • Journal of Animal Science and Technology
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    • v.51 no.1
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    • pp.9-14
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    • 2009
  • Insulin-like growth factor 2 (IGF2) is the first identified imprinted gene, which is paternally expressed in multiple mammalian species. A paternally expressed QTL for muscle growth and backfat thickness (BFT) has previously been identified near the IGF2 locus on the distal tip of pig chromosome 2 (SSC2p). Therefore the IGF2 gene is considered an economically important candidate gene for pig industry. Herein, this study explored genetic variation of IGF2 for in3-G3072A, in7-G162C and a new SNP in intron7 (C1589T) in Korean native pig (KNP) and commercial pig breeds, and detected their linkage disequilibrium within these breeds. Furthermore we investigated the effect of in3-G3072A on IGF2 gene expression in post-natal muscle and backfat tissues. The real-time quantitative PCR results showed that animals inherited allele G from a KNP sire had significant higher IGF2 gene expression in backfat tissue than those inherited allele A from a Yorkshire sire, however opposite situation in muscle. These results demonstrated the allele 3072G is associated with a higher IGF2 gene expression in fat tissues, but low gene expression in muscle tissues when compared with the 3072A allele. These results suggest that KNP with lower muscle mass and higher fat deposition might be associated with a higher frequency of the 3072G allele, and selecting KNP based on IGF2 genotypes could result in an economic benefit to KNP producers.

Regulatory Mechanism of Radiation-induced Cancer Cell Death by the Change of Cell Cycle (세포주기 변화에 타른 방사선 유도 암세포 사망의 조절기전)

  • Jeong Soo-Jin;Jeong Min-Ho;Jang Ji-Yeon;Jo Wol-Soon;Nam Byung-Hyouk;Jeong Min-Za;Lim Young-Jin;Jang Byung Gon;Youn Seon-Min;Lee Hyung Sik;Hur Won Joo;Yang Kwang Mo
    • Radiation Oncology Journal
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    • v.21 no.4
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    • pp.306-314
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    • 2003
  • Purpose : In our Previous study, we have shown the main cel1 death pattern Induced by irradiation or protein tyrosine kinase (PTK) inhibitors in K562 human myeiogenous leukemic cell line. Death of the cells treated with irradiation alone was characterized by mitotic catastrophe and typical radiation-induced apoptosis was accelerated by herblmycin A (HMA). Both types of cell death were inhibited by genistein. In this study, we investigated the effects of HMA and genistein on cell cycle regulation and its correlation with the alterations of radiation-induced cell death. Materials and Methods: K562 cells In exponential growth phase were used for this study. The cells were Irradiated with 10 Gy using 6 MeV Linac (200-300 cGy/min). Immediately after irradiation, cells were treated with 250 nM of HMA or 25 $\mu$N of genistein. The distributions of cell cycle, the expressions of cell cycle-related protein, the activities of cyclin-dependent kinase, and the yield of senescence and differentiation were analyzed. Results: X-irradiated cells were arrested In the G2 phase of the cell cycle but unlike the p53-positive cells, they were not able to sustain the cell cycle arrest. An accumulation of cells in G2 phase of first ceil-cycle post-treatment and an increase of cyclin Bl were correlated with spontaneous, premature, chromosome condensation and mitotic catastrophe. HMA induced rapid G2 checkpoint abrogation and concomitant p53-independent Gl accumulation. HMA-induced cell cycle modifications correlated with the increase of CDK2 kinase activity, the decrease of the expressions of cyclins I and A and of CDK2 kinase activity, and the enhancement of radiation-induced apoptosis. Genistein maintained cells that were arrested in the G2-phase, decreased the expressions of cyclin Bl and cdc25c and cdc25C kinase activity, increased the expression of pl6, and sustained senescence and megakaryocytic differentiation. Conclusion: The effects of HMA and genistein on the radiation-induced cell death of KS62 cells were closely related to the cell cycle regulatory activities. In this study, we present a unique and reproducible model in which for investigating the mechanisms of various, radiation-induced, cancer cell death patterns. Further evaluation by using this model will provide a potent target for a new strategy of radiotherapy.

Analysis of Quantitative Trait Loci (QTLs) for Seed Size and Fatty Acid Composition Using Recombinant Inbred Lines in Soybean (콩 재조합자식계통을 이용한 콩 종자의 크기와 지방산 조성의 양적 형질 유전자좌 분석)

  • Kim, Hyeun-Kyeung;Kim, Yong-Chul;Kim, Sun-Tae;Son, Beung-Gu;Choi, Yong-Whan;Kang, Jum-Soon;Park, Young-Hoon;Cho, Young-Son;Choi, In-Soo
    • Journal of Life Science
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    • v.20 no.8
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    • pp.1186-1192
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    • 2010
  • Soybean [Glycine max(L.) Merr.] is an important crop, accounting for 48% of the world market in oil crops. Improvements in economic traits, such as quality and oil constituents, arethe most important objectives in soybean breeding. The objective of this study was to identify quantitative trait loci (QTLs) that control seed size and fatty acid contents in soybean. 115 $F_{2:10}$ recombinant inbred lines (RIL) developed from a cross of 'Keunolkong' and 'Iksan10' were used. Narrow-sense heritability estimates based on a plot mean on 100 seed weight, saturated fatty acid (palmitic acid + stearic acid), and oleic, linoleic, and linolenic acid content were 0.72, 0.60, 0.83, 0.77 and 0.81, respectively. The 100 seeds weight was related to seven QTLs located on chromosomes 1, 3, 8, 9, 16 and 17. Two independent QTLs for saturated fatty acid content were identified on chromosomes 17 and 19. Five independent QTLs for oleic acid content wereidentified on chromosomes7, 11, 14, 16 and 19. Five QTLs for linoleic acid content were located on chromosomes 2, 11, 14, 16 and 19. Three QTLs for linolenic acid content were located on chromosomes 8, 10 and 19. Oleic, linoleic, and linolenic acid had one major common QTL on chromosome 19. Thus, linoleic and linolenic acid content were identified as common QTLs.

Analysis of Telomere Length and Telomerase Activity of Tissues in Korean Native Chicken (한국 재래닭의 주령별 각 조직의 텔로미어 함량과 텔로머레이스 활성도 분석)

  • Jung G.S.;Cho E.J.;Choi D.S.;Lee M.J.;Park C.;Jeon I.S.;Sohn S.H.
    • Korean Journal of Poultry Science
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    • v.33 no.2
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    • pp.97-103
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    • 2006
  • Telomeres are essential for chromosome stability and are related with cell senescence, apoptosis and cancer. Even though telomere length and telomerase activity have been studied extensively, very little is known to analyze the telomere dynamics in chicken cells. This study was carried out to analyze the telomere distribution and telomerase activity of Korean Native Chicken cells along with aging. The cells were collected from brain, heart, liver, kidney and germinal tissues during physiological stages. Telomere distribution was analyzed by Quantitative-Fluorescence in situ Hybridization (Q-FISH) techniques using the chicken telomeric DNA probe. Telomerase activity was performed by Telomeric Repeat Amplification Protocol (TRAP) assay. In results, the telomeres of chicken were found at the ends of all chromosomes with the interstitial telomeres on chromosomes 1, 2 and 3. The amount of telomeres on chicken cells was decreased along with aging in most tissues. Furthermore, the telomere quantity was significantly different among tissues. The relative amount of telomeres in proliferous cells such as testis cells had much more than those of liver, brain, heart, blood and kidney cells. The telomerase activity was down-regulated in cells of brain, heart and liver tissues. Whereas gonadal cells showed a constitutive activity of telomerase during all stage of life. In conclusions, the telomere quantity and telomerase activity in chicken are closely relate to cell proliferation and tissue specificity during developmental stages and aging. There is also closely correlated between the amounts of telomeric DNA and telomerase activity in chicken tissues.

Cattle Age Prediction by Leukocytes Telomere Quantification (혈액세포의 텔로미어 함량을 이용한 소의 연령예측)

  • Choi, Na-Eun;Kim, Hyun-Sub;Choe, Chang-Yong;Jeon, Gwang-Joo;Sohn, Sea-Hwan
    • Journal of Animal Science and Technology
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    • v.52 no.5
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    • pp.367-374
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    • 2010
  • Telomeres at the end of chromosomes consist of tandem repeats of (TTAGGG)n DNA sequence and associated proteins. Telomeres have the essential functions in chromosome stability and genome integrity and are hence related to cell senescence and cancer. This study was carried out to quantify the amount of telomeric DNA and establish age prediction equations by using the quantity of telomeric DNA for cattle. Analysis of the telomere quantity of the lymphocytes was performed at different age, across breeds and between different sexes of cattle. We quantified the amount of telomeric DNA by the Q-FISH technique using the telomeric DNA probe in 460 cattle at age of 1~166 months in Korean Cattle and Holstein breeds. In results, we found that the amount of telomeric DNA decreased gradually with age. The amount of telomeric DNA of Korean Cattle was significantly higher than that of Holstein breed (P<0.01). In addition, the amount of telomeric DNA in male was significantly higher than that in female (P<0.01). Using the relationship between age and the amount of telomeric DNA in cattle, age predicting equations were established as a result of regression analysis. Because sex and breeds influenced telomeric DNA quantity, the age prediction equations were estimated separately in Korean Cattle females and Holstein females. The regression equations were $\hat{Y}$=$38.102X^2$-220.103X + 318.309 (P<0.0001, $R^2$=0.8019) in Korean Cattle females and $\hat{Y}$ = $42.799X^2$ - 199.682X + 242.106 (P<0.0001, $R^2$ = 0.8379) in Holstein females, where the X was quantity of telomeric DNA and Y was predicted age in months. These equations predicted the age of cattle with high significance and accuracy and have high R square values. Thus, it could be possible to scientifically predict the age using the above equations for Korean Cattle and Holstein females.

A Comparison Study of Metaphase Analysis of Chromosomal Aberration and Flow Cytometric Assessment of Radiation-induced Apoptosis in Human Peripheral Lymphocytes (인체 말초혈액 림프구에서 방사선유도 염색체 손상 및 세포고사에 대한 중기염색체 분석 및 유세포계측 연구)

  • Bom, Hee-Seung;Lee, Seung-Yeon;Lee, Sang-Ku;Min, Jung-Jun;Jeong, Hwan-Jeong;Song, Ho-Cheon;Kim, Ji-Yeul;Shin, Jong-Hee;Suh, Sun-Pal;Rhang, Dong-Wook
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.1
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    • pp.94-99
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    • 1999
  • Purpose: Radiation-induced chromosomal damage and apoptosis were compared in human lymphocytes. Materials and Methods: Peripheral lymphocytes from 10 normal volunteers (6 males, 4 females, age range $23{\sim}41$ years) were irradiated by gamma rays from a cell irradiator. Doses of irradiation were 0 (control), 0.18, 2, 5, 10, 20 and 25 Gy. Irradiated lymphocytes were examined by metaphase analysis for chromosomal aberrations and by flow cytometry for apoptosis. Results of both studies were compared according to dose. Results: Number of dicentric and ring chromosomes (D+R) was $0.5{\pm}0.53$ at baseline, which was significantly increased after radiation according to the dose. The fraction of cells showing annexin V-fluorescein isothiocyanate uptake was $0.51{\pm}$0.39%, which increased to $3.58{\pm}1.85%$ by 2 Gy irradiation, and then decreased. The fraction of cells showing propidium iodide (PI) uptake was $0.52{\pm}0.12%$, which significantly increased according to dose (upto $15.64{\pm}5.99%$ by 20 Gy irradiation). D+R and PI uptake were well correlated (r=0.84, p<0.001). Conclusion: Radiation-induced chromosomal aberration was correlated to nuclear uptake of PI, a marker of late apoptosis.

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Bankruptcy prediction using an improved bagging ensemble (개선된 배깅 앙상블을 활용한 기업부도예측)

  • Min, Sung-Hwan
    • Journal of Intelligence and Information Systems
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    • v.20 no.4
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    • pp.121-139
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    • 2014
  • Predicting corporate failure has been an important topic in accounting and finance. The costs associated with bankruptcy are high, so the accuracy of bankruptcy prediction is greatly important for financial institutions. Lots of researchers have dealt with the topic associated with bankruptcy prediction in the past three decades. The current research attempts to use ensemble models for improving the performance of bankruptcy prediction. Ensemble classification is to combine individually trained classifiers in order to gain more accurate prediction than individual models. Ensemble techniques are shown to be very useful for improving the generalization ability of the classifier. Bagging is the most commonly used methods for constructing ensemble classifiers. In bagging, the different training data subsets are randomly drawn with replacement from the original training dataset. Base classifiers are trained on the different bootstrap samples. Instance selection is to select critical instances while deleting and removing irrelevant and harmful instances from the original set. Instance selection and bagging are quite well known in data mining. However, few studies have dealt with the integration of instance selection and bagging. This study proposes an improved bagging ensemble based on instance selection using genetic algorithms (GA) for improving the performance of SVM. GA is an efficient optimization procedure based on the theory of natural selection and evolution. GA uses the idea of survival of the fittest by progressively accepting better solutions to the problems. GA searches by maintaining a population of solutions from which better solutions are created rather than making incremental changes to a single solution to the problem. The initial solution population is generated randomly and evolves into the next generation by genetic operators such as selection, crossover and mutation. The solutions coded by strings are evaluated by the fitness function. The proposed model consists of two phases: GA based Instance Selection and Instance based Bagging. In the first phase, GA is used to select optimal instance subset that is used as input data of bagging model. In this study, the chromosome is encoded as a form of binary string for the instance subset. In this phase, the population size was set to 100 while maximum number of generations was set to 150. We set the crossover rate and mutation rate to 0.7 and 0.1 respectively. We used the prediction accuracy of model as the fitness function of GA. SVM model is trained on training data set using the selected instance subset. The prediction accuracy of SVM model over test data set is used as fitness value in order to avoid overfitting. In the second phase, we used the optimal instance subset selected in the first phase as input data of bagging model. We used SVM model as base classifier for bagging ensemble. The majority voting scheme was used as a combining method in this study. This study applies the proposed model to the bankruptcy prediction problem using a real data set from Korean companies. The research data used in this study contains 1832 externally non-audited firms which filed for bankruptcy (916 cases) and non-bankruptcy (916 cases). Financial ratios categorized as stability, profitability, growth, activity and cash flow were investigated through literature review and basic statistical methods and we selected 8 financial ratios as the final input variables. We separated the whole data into three subsets as training, test and validation data set. In this study, we compared the proposed model with several comparative models including the simple individual SVM model, the simple bagging model and the instance selection based SVM model. The McNemar tests were used to examine whether the proposed model significantly outperforms the other models. The experimental results show that the proposed model outperforms the other models.

Effects of SNP in TSH-β Gene of Chicken on Economic Traits (닭의 경제 형질에 미치는 TSH-β 유전자 변이 효과 분석)

  • Seo, Joohee;Oh, Jae Don;Choi, Eun Ji;Lim, Hee Kyong;Seong, Jiyeon;Song, Ki Duk;Lee, Jun Heon;Lee, Hak Kyo;Kong, Hong Sik;Jeon, Gwang Joo;Shon, Young Gon;Choi, Kang Duk
    • Korean Journal of Poultry Science
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    • v.40 no.2
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    • pp.115-120
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    • 2013
  • Thyroid hormone (TH) plays a role in growth of the poultry. Thyroid-stimulating hormone (TSH) stimulates production and distribution of TH, and is a heterodimer which is formed by ${\alpha}$- and ${\beta}$-subunits. Most of TSH activity is known to rely on ${\beta}$-subunit. TSH-${\beta}$ gene is located on chicken chromosome 26 and associated with growth performances. Therefore, this study aimed to investigate the association of TSH- ${\beta}$ SNP (G1031C) with economic traits (layday, layw, layno, bw150, bw270, layw270) in Korean Native Black chicken, Rhode Island Red and Cornish. Allele frequency of GG genotype in Rhode Island Red (RIR) was found to be 1.00 in this study. A significant effect was only observed on body weight at day 150 in Cornish. In Cornish, body weights of chicken with the CC genotype ($302.15{\pm}6.336$) were significantly higher than that of the GG genotype ($294.56{\pm}4.537$) (p<0.05). These findings suggest that the G1031C SNP of TSH-${\beta}$ gene can be used for improvement of growth-related traits in Cornish.

Genome Wide Association Study to Identity QTL for Growth Taits in Hanwoo (전장 유전체 연관분석을 통한 한우 성장 연관 양적형질좌위 (QTL) 탐색)

  • Lee, Seung Hwan;Lim, Dajeong;Jang, Gul Won;Cho, Yong Min;Choi, Bong Hwan;Kim, Si Dong;Oh, Sung Jong;Lee, Jun Heon;Yoon, Duhak;Park, Eung Woo;Lee, Hak Kyo;Hong, Seong Koo;Yang, Boh Suk
    • Journal of Animal Science and Technology
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    • v.54 no.5
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    • pp.323-329
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    • 2012
  • Genome-wide association study was performed on data from 266 Hanwoo steers derived from 66 sires using bovine 10K mapping chip in Hanwoo (Korean cattle). SNPs were excluded from the analysis if they failed in over 5% of the genotypes, had median GC scores below 0.6, had GC scores under 0.6 in less than 90% of the samples, deviated in heterozygosity more than 3 standard deviations from the other SNPs and were out of Hardy-Weinberg equilibrium for a cut-off p-value of $1^{-15}$. Unmapped and SNPs on sex chromosomes were also excluded. A total of 4,522 SNPs were included in the analysis. To test an association between SNP and QTL, a single marker regression analysis was implemented in this study. SNP was assumed to be in LD with QTL in close proximity and the effect evaluated was additive effect (QTL allele substitution effect). The number of significant SNP at a threshold of P<0.001 was 3, 5, 5 and 4 loci for live weight at 6, 12, 18 and 24 months, respectively. For live weight at different ages, significant SNP were spread out across chromosome but some of significant SNP (rs29012453 and rs29012456 on BTA24) had shown highly significant effects. As for the distribution of size of SNP effects, few loci for live weight at different age had moderate effects (6~11%) but most of significant loci had small effects (2 to 5% of additive genetic variance) against total additive genetic variance. In conclusion, live weight at different age might be affected by few loci with moderate effect and many loci with small effects across genome in Hanwoo.