• Tuberculosis and Respiratory Diseases
• /
• v.61 no.3
• /
• pp.248-255
• /
• 2006

Background: LOH11A is a region with frequent allele loss (>75%) in lung cancer that is located on the centromeric part of chromosome 11p15.5. Clinical and cell biological studies suggest that this region contains a gene associated with metastatic tumor spread. RRM1 encoding the M1 subunit of ribonucleotide reductase, which is an enzyme that catalyses the rate-limiting step in deoxyribonucleotide synthesis, is located in the LOH11A region. Methods: Polymorphisms were found at nucleotide position (-)37 (C/A) and (-)524 (C/T) from the beginning of exon 1 of the RRM1 gene that might regulate the expression of RRM1. We studied the polymorphisms in 127 Korean individuals (66 lung cancer and 61 normal controls) and compared with those of 140 American patients with lung cancer. Results: CC, AC and AA were found at the (-)37 position in 64(50.4%), 55(43.3%), and 8(6.3%) out of 127 Korean individuals (66 cancer, 61 non-cancer patients), respectively. There was a similar frequency of allele A at (-)37 in the American(27.9%) and Korean population(28.0%). CC, CT and TT was found at the (-)524 position in 24(18.9%), 44(34.6%), and 59(46.5%) out of the 127 Korean individuals, respectively. There was a similar frequency of allele C at (-)524 in the American(34.6%) and Korean population(36.2%). There was no difference in the frequency of the (-)37 and (-)524 genotypes between the cancer and non-cancer group. However there was a significant correlation of the genotypes between (-)37 and (-)524 (p<0.001), which suggests the possible coordination of these polymorphisms in the regulation of the promoter activity of the RRM1 gene. Conclusion: RRM1 promoter polymorphisms were not found to be significant risk factors for lung cancer. However, a further study of the promoter activity and expression of the RRM1 gene according to the pattern of the polymorphism will be needed.

• Childhood Kidney Diseases
• /
• v.3 no.2
• /
• pp.209-216
• /
• 1999

Purpose : Nephrogenic diabetes insipidus (NDI) is a rare X-linked disorder associated with renal tubule resistance to arginine vasopressin (AVP). The hypothesis that the defect underlying NDI might be a dysfunctional renal AVPR2 has recently been proven by the identification of mutations in the AVPR2 gene in NDT patients. To investigate the association of mutations in th AVPR2 gene with NDI, we analyzed the AVPR2 gene located on the X chromosome. Methods : We have analyzed the AVPR2 gene in a kindred with X-linked NDI. The proband and proband's mother were analyzed by polymerase chain reaction-single strand conformational polymorphism(PCR-SSCP) and DNA sequencing of the AVPR2 gene. We also have used restriction enzyme analysis of genomic PCR product to evaluate the AVPR2 gene. Results : C to T transition at codon 202, predictive of an exchange of tryptophan 202 by cysteine(R202C) in the third extracellular domain was identified. This mutation causes a loss of Hae III site within the gene. Conclusion : We found a R202C missense mutation in the AVPR2 gene causing X-linked NDI, and now direct mutational analysis is available for carrier screening and early diagnosis.

• Reproductive and Developmental Biology
• /
• v.29 no.3
• /
• pp.175-180
• /
• 2005

This study was conducted to examine the effects of demecolcine-assisted enucleation and recipient cell cycle stage on the development of bovine somatic cell nuclear transfer (NT) embryos. In vitro cultured oocytes for $16\~20$ h were classified by first polar body (1st PB) extrusion and cell cycle stage (MI and MII) and treated $0.4\;{\mu}L/mL$ demecolcine for 40 min before enucleation. Enucleated oocytes were fused electrically with bovine ear skin cells, activated by Ca-ionophore+DMAP, and cultured in vitro. Most of eggs ($86.2\%$) treated with demecolcine protruded a chromosome mass and enucleated efficiently ($98.8\%$, (P<0.05). Demecolcine did not have a deteriorative effect on the development of NT embryos. Developmental rate of NT embryos reconstituted with oocytes extruded 1st PB significantly higher than that of NT embryos produced by oocytes without 1st PB ($18.2\%\;vs.\;4.6\%\cdot$, P<0.05). Cleavage and blastocyst formation rate of embryos reconstituted with MI oocytes ($69.4\%\;and\;5.9\%$, respectively) were significantly lower than those of embryos reconstituted with MII oocytes ($96.7\%\;and\;23.9\%$, respectively, P<0.05). From the present result, it is suggested that domecolcine is useful for the enucleation of recipient oocytes in bovine NT procedures, and MII oocytes rather than MI oocytes are more appropriate for recipient cytoplasm. Although, the potential to develop into blastocysts of NT embryos produced by 1st PB-nonextruded and MI oocytes was very low, these oorytes could be used for NT.

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.2
• /
• pp.150-160
• /
• 1999

Background: The CREST syndrome is an indolent form of progressive systemic sclerosis. Although its clinical progress is indolent, pulmonary hypertension(PH) associated with CREST syndrome have grave prognosis with over 40 percent mortality rate at 2 year follow-up. But the pathogenesis of pulmonary hypertension in this disease is not known, and classified as either primary or secondary PH. Clonality of endothelial cell proliferation in plexiform lesion is a molecular marker which allows distinction between primary and secondary PH. We performed this study to know whether the PH associated with CREST syndrome is a variant of primary PH or is a secondary PH. Methods: We assessed the X-chromosome inactivation based on the methylation pattern of the human androgen-receptor gene by PCR(HUMARA). Endothelial cells in plexiform lesions from female patients(n=3) with PH associated with CREST syndrome were microdissected from paraffin blocks. Vascular smooth muscle cells and lung parenchyma were also microdissected for clonality studies. Results: The proliferating endothelial cells in 14 plexiform lesions were all polyclonal. Similarly proliferated smooth muscle cells from 5 vessels with medial hypertrophy were also polyclonal. Conclusion: These results suggest that the pulmonary hypertension associated with CREST syndrome has different pathogenesis from primary PH and to be classified as secondary PH.

• Horticultural Science & Technology
• /
• v.30 no.5
• /
• pp.557-567
• /
• 2012

This study was conducted to achieve basal information for the development of tomato cultivars with disease resistances through marker-assisted backcross (MAB). Ten inbred lines with TYLCV, late blight, bacterial wilt, or powdery mildew resistance and four adapted inbred lines with superior horticultural traits were collected, which can be useful as the donor parents and recurrent parents in MAB, respectively. Inbred lines collected were evaluated by molecular markers and bioassay for confirming their disease resistances. To develop DNA markers for selecting recurrent parent genome (background selection) in MAB, a total of 108 simple sequence repeat (SSR) primer sets (nine per chromosome at average) were selected from the tomato reference genetic maps posted on SOL Genomics Network. Genetic similarity and relationships among the inbred lines were assessed using a total of 303 polymorphic SSR markers. Similarity coefficient ranged from 0.33 to 0.80; the highest similarity coefficient (0.80) was found between bacterial wilt-resistant donor lines '10BA333' and '10BA424', and the lowest (0.33) between a late blight resistant-wild species L3708 (S. pimpinelliforium L.) and '10BA424'. UPGMA analysis grouped the inbred lines into three clusters based on the similarity coefficient 0.58. Most of the donor lines of the same resistance were closely related, indicating the possibility that these lines were developed using a common resistance source. Parent combinations (donor parent ${\times}$ recurrent parent) showing appropriate levels of genetic distance and SSR marker polymorphism for MAB were selected based on the dendrogram. These combinations included 'TYR1' ${\times}$ 'RPL1' for TYLCV, '10BA333' or '10BA424' ${\times}$ 'RPL2' for bacterial wilt, and 'KNU12' ${\times}$ 'AV107-4' or 'RPL2' for powdery mildew. For late blight, the wild species resistant line 'L3708' was distantly related to all recurrent parental lines, and a suitable parent combination for MAB was 'L3708' ${\times}$ 'AV107-4', which showed a similarity coefficient of 0.41 and 45 polymorphic SSR markers.

• Korean Journal of Biological Psychiatry
• /
• v.21 no.3
• /
• pp.99-106
• /
• 2014

Objectives Previous studies suggest that the cannabinoid receptor 1 (CNR1) gene could be an important candidate gene for schizophrenia. According to linkage studies, this gene is located on chromosome 6q14-q15, which is known to harbor the schizophrenia susceptibility locus (locus 5, SCZ5, OMIM 803175). The pharmacological agent delta-9-tetrahydrocannabinol (${\Delta}$-9-THC) seems to elicit the symptoms of schizophrenia. The association between CNR1 polymorphisms and schizophrenia is actively being investigated, and some studies have linked the AAT-trinucleotide repeats in CNR1 to the onset of schizophrenia. In this study, we have investigated the association between the AAT-trinucleotide repeats in CNR1 and schizophrenia by studying schizophrenia patients and healthy individuals from Korea. Methods DNA was extracted from the blood samples of 394 control subjects and 337 patients diagnosed with schizophrenia (as per the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria). After polymerase chain reaction amplification, a logistic regression analysis, with age and gender as the covariates, was performed to study the variations in the AAT-repeat polymorphisms between the two groups. Results In total, 8 types of trinucleotide repeats were identified, each containing 7, 8, 10, 11, 12, 13, 14, and 15 repeats, respectively. $(AAT)_{13}$ allele was most frequently observed, with a frequency of 33.6% and 31.6% in the patient and control groups, respectively. The frequency of the other repeat alleles in the patient group (in the decreasing order) was as follows : $(AAT)_{13}$ 33.6%, $(AAT)_{14}$ 21.6%, $(AAT)_{12}$ 18.5%, and $(AAT)_{7}$ 11.1%. The frequency of the repeat alleles in the control group (in the decreasing order) was as follows : $(AAT)_{13}$ 31.6%, $(AAT)_{14}$ 24.5%, $(AAT)_{12}$ 17.2%, and $(AAT)_{7}$ 11.6%. However, there were no significant differences in the AAT-repeat polymorphisms of the CNR1 gene between the patient group and the control group. Conclusions Although our study revealed no significant association of the AAT-repeat polymorphism of the CNR1 gene with schizophrenia, it will serve as a good reference for future studies designed to examine the cannabinoid hypothesis of schizophrenia.

• Journal of Animal Science and Technology
• /
• v.53 no.1
• /
• pp.1-6
• /
• 2011

This simulation study was performed to investigate the accuracy of the estimated breeding value by using genomic information (GEBV) by way of Bayesian framework. Genomic information by way of single nucleotide polymorphism (SNP) from a chromosome with length of 100cM were simulated with different marker distance (0.1cM, 0.5cM), heritabilities (0.1, 0.5) and half sibs families (20 heads, 4 heads). For generating the simulated population in which animals were inferred to genomic polymorphism, we assumed that the number of quantitative trait loci (QTL) were equal with the number of no effect markers. The positions of markers and QTLs were located with even and scatter distances, respectively. The accuracies of estimated breeding values by way of indicating correlations between true and estimated breeding values were compared on several cases of marker distances, heritabilities and family sizes. The accuracies of breeding values on animals only having genomic information were 0.87 and 0.81 in marker distances of 0.1cM and 0.5cM, respectively. These accuracies were shown to be influenced by heritabilities (0.87 at $h^2$ =0.10, 0.94 at $h^2$ =0.50). According to half sibs' family size, these accuracies were 0.87 and 0.84 in family size of 20 and 4, respectively. As half sibs family size is high, accuracy of breeding appeared high. Based on the results of this study it is concluded that the amount of marker information, heritability and family size would influence the accuracy of the estimated breeding values in genomic selection methodology for animal breeding.

• The Korean Journal of Nuclear Medicine
• /
• v.33 no.1
• /
• pp.94-99
• /
• 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.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.15 no.1
• /
• pp.29-34
• /
• 2015

Citrullinemia type1 is an autosomal recessive disorder of the urea cycle characterized by neonatal or late onset of hyperammonemia caused by a deficiency of the enzyme argininosuccinate synthetase (ASS). An ASS1 deficiency demonstrates fatal clinical manifestations that are characterized by the neonatal metabolic coma and early death when untreated. It causes a broad spectrum of effects, ranging from a mild disorder to a severe mental retardation, epilepsy, neurologic deficits. An acute neonatal form is the most common. Infants are normal at birth followed by an acute illness characterized by vomiting, lethargy, seizures and coma. These medical problems are life-threatening in many cases. A later onset form is less frequent and may be milder than the neonatal form. This later-onset form is associated with severe headaches, visual dysfunction, motor dysfunction, and lack of energy. Citrullinemia type1 is caused by mutations in the ASS1 gene located on chromosome 9q34.1 that encodes argininosuccinate synthetase, the third enzyme of the urea cycle catalyzing the formation of argininosuccinic acid from citrulline and aspartic acid. The enzyme is distributed in tissues including liver and fibroblasts. This mutation leads to hyperammonemia, arginine deficiency and elevated citrulline level. In the urea cycle, argininosuccinate synthetase catalyses the conversion of citrulline and aspartate to argininosuccinate.. Here, we describe a female newborn patient with lethargy, rigidity and hyperammonemia who was diagnosed as citrullinemia type1 with a c.[421-2A>G], c.[1128-6_1188dup] mutation.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.3
• /
• pp.338-349
• /
• 1999

Polymorphonuclear leukocytes(PMN) are the predominant inflammatory cells recruited in acute lung injury such as adult respiratory distress syndrome, pneumonia and also chronic lung disease such as idiopathic pulmonary fibrosis and pulmonary emphysema. Interleukin-8(IL-8) is an 8,000 D protein produced by many cells and has potent neutrophil chemoattractant and activating properties. The GRO, also called melanoma growth-stimulatory activity(MGSA), referring to a peptide of 73 amino acids, was reported to be mitogenic for cultured human melanoma cells. Mature GRO/MGSA has marked sequence similarity to IL-8. In view of the structural similarities to IL-8, it was of particular interest to test GRO for neutrophil activating and chemotactic properties. We found a significant release of IL-8 and GRO/MGSA from the cultured human umbilical vein endothelial cell(HUVEC) which was stimulated either with TNF$\alpha$ or IL-1$\beta$ and also found the expression of IL-8 and GRO/MGSA mRNA. Neutrophil chemotactic activity was enhanced in accordance with the increased IL-8 and GRO/MGSA. Our study also suggest that the IL-8 is more important in the increased neutrophil chemotactic activity than GRO/MGSA when endothelial cell is stimulated with TNF$\alpha$ or IL-1$\beta$ in vitro.