• Biomedical Science Letters
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• v.26 no.1
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• pp.28-36
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• 2020

High blood pressure (HTN) is a condition in which blood pressure is kept higher than normal. Blood pressure trait measures systolic blood pressure (SBP) which is the highest pressure and diastolic blood pressure (DBP) which is the lowest blood pressure. Pulse pressure (PP) is the difference between systolic and diastolic blood pressure. Hypertension is known as a disease caused by the interaction of the environment and genetic factors. To date, studies have been conducted to find genes associated with hypertension. Genome-Wide Association Study (GWAS) analysis using European data from the UK Biobank reported new 535 loci were associated with blood pressure trait. Among them, 12 genes have been reported to have a significant correlation with SBP, DBP and PP. In the study, 12 genes polymorphisms were extracted based on KARE (Korean association resource) and then we performed linear regression of blood pressure trait. As a result, 6 SNPs of the 3 genes (rs12355413 and rs11006736 of ARMC4, rs2290883, rs2290884 and rs11039014 of LRP4, rs7234941 of BCL2) showed statistically significant correlation (P<0.05) with blood pressure trait. Of the 3 genes, 6 SNPs in 2 genes (rs9651357, rs12355413, rs11006736, rs1889522 of ARMC4 and rs4987774, rs7234941 of BCL2) showed significant correlation with hypertension. These results suggest that genetic polymorphisms of ARMC4, LRP4 and BCL2 genes are associated with blood pressure traits and hypertension in Korean population. Moreover, we expected to help understand the pathogenesis of hypertension.

• Korean journal of dermatology
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• v.56 no.10
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• pp.609-613
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• 2018

Background: Psoriasis is a chronic inflammatory skin disease with an incidence of 0.5~3% of the worldwide population. The pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune reactions. Notably, genetic factors are considered important etiological contributors. Globally, several researchers have recently performed genome-wide association studies (GWAS) to identify the genes related with psoriasis. Objective: We aimed to investigate the expression pattern of 2 candidate genes that were identified by GWAS. These include interleukin 28 receptor alpha (IL28RA) and CUB and Sushi multiple domains 1 (CSMD1). Methods: We applied imiquimod cream to develop a psoriasis-like mouse model and obtained skin tissue. We performed immunohistochemistry to detect the expression of IL-28A and CSMD1. Results: IL28RA expression increased at an early time point such as 1 day after the topical application of 5% imiquimod cream. However, its expression returned to baseline levels 2 weeks after the topical application of imiquimod cream. CSMD1 expression also increased after the topical application of imiquimod, with increased expression particularly observed in the upper epidermal layer. Notably, CSMD1 expression decreased 7 days after imiquimod cream application. Conclusion: These results suggest that IL28RA and CSMD1 may play key roles in the pathogenesis of psoriasis.

• Journal of Preventive Medicine and Public Health
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• v.49 no.5
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• pp.253-259
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• 2016

Objectives: Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1), which was associated with central obesity-related traits via interactions with stress levels. We aimed to evaluate EBF1 gene-by-stress interaction effects on central adiposity traits, including visceral adipose tissue (VAT), in Korean adults. Methods: A total of 1467 Korean adults were included in this study. We selected 22 single-nucleotide polymorphisms (SNPs) in the EBF1 gene and analyzed their interactions with stress on central adiposity using additive, dominant, and recessive genetic modeling. Results: The four SNPs that had strong linkage disequilibrium relationships (rs10061900, rs10070743, rs4704967, and rs10056564) demonstrated significant interactions with the waist-hip ratio in the dominant model ($p_{int}$<0.007). In addition, two other SNPs (rs6556377 and rs13180086) were associated with VAT by interactions with stress levels, especially in the recessive genetic model ($p_{int}$<0.007). As stress levels increased, the mean values of central adiposity traits according to SNP genotypes exhibited gradual but significant changes (p<0.05). Conclusions: These results suggest that the common genetic variants for EBF1 are associated with central adiposity through interactions with stress levels, emphasizing the importance of managing stress in the prevention of central obesity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4905-4908
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• 2012

Aim: Glioma cancer is the most common type of adult brain tumor. Recent genome-wide association studies (GWAS) have identified various new susceptibility regions and here we conducted an extensive analysis of associations between 12 single nucleotide polymorphisms (SNPs) and glioma risk. Methods: A total of 197 glioma cases and 197 health controls were selected, and 9 SNPs in 8 genes were analyzed using the Sequenom MassARRAY platform and Sequenom Assay Design 3.1 software. Results: We found the MAF among selected controls were consistent with the MAF from the NCBI SNP database. Among 9 SNPs in 8 genes, we identified four significant SNP genotypes associated with the risk of glioma, C/C genotype at rs730437 and T/T genotype at rs1468727 in ERGF were protective against glioma, whereas the T/T genotype at rs1799782 in XRCC1 and C/C genotype at rs861539 in XRCC3 conferred elevated risk. Conclusion: Our comprehensive analysis of nine SNPs in eight genes suggests that the rs730437 and rs1468727 in ERGF, rs1799782 in XRCC1 gene, and rs861539 in XRCC3 gene are associated with glioma risk. These findings indicate that genetic variants of various genes play a complex role in the development of glioma.

• Biomedical Science Letters
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• v.21 no.3
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• pp.135-143
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• 2015

Electrocardiogram measures the electric impulses generated by the heart during its cycle. Recently genome-wide association studies on electrocardiogram traits revealed many relevant genetic loci. Therefore, these findings need to be validated and investigated to determine the underlying mechanisms using mouse models. Invasive radiotelemetry has been widely used to record the electrocardiogram in mice because it has several advantages over non-invasive measurements. However, radiotelemetry is expensive and requires complicated surgery. On the other hand, a non-invasive method using 3 electrodes (one for earth) for lead II is easy to establish and allows for rapid measurement. In this study, eleven mice were measured with this non-invasive method and no statistical difference among them was found in any ECG measurements. In addition, repeat measurement in the same mouse was performed in 9 sets of experiment and the results indicated that non-invasive method was reliable for reproducibility. Further it was shown that measurements for 1, 5, 10, and 15 minutes were not different so that a short recording such as 5 minutes was enough to estimate the ECG values including heart rate. Further this method was validated by measuring the ECG of Balb/c and FVB that were previously shown to differ in ECG values by radiotelemetry. Significant differences were found in heart rate, PR interval and corrected QT interval between these mouse strains. This study partially proved that non-invasive method also could provide the accuracy and reproducibility. Based on these results, the non-invasive ECG recordings of lead II is recommended as a useful method for quick test in mouse model.

• Korean Journal of Agricultural Science
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• v.47 no.3
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• pp.667-672
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• 2020

It is well known that intensive selection caused a decline in reproductive performance in dairy cattle. Interestingly, the reproductive performances including fertility and calving interval of Korean native beef cattle have declined in the last 20 years, suggesting that a breeding program focusing on carcass weight and intramuscular fat may affect the reproductive physiology in Korean native beef cattle, too. In this study, we analyzed the calving interval (CI) and selection index (SI) based on genome-wide association studies (GWAS) of Hanwoo cows for seven years (2013 - 2019). Multiparous cows (4.5 ± 0.11) were analyzed, which were bred by artificial insemination (AI). We first examined the distribution of the AIs and calving dates. About 40% of the AIs were carried out in May to June and October to December; subsequently, calving was observed from March to April and August to October, respectively, indicating the cows were seasonally bred. No correlation between CI and SI was found (y = 0.0459x - 17.64; R² = 0.0356), but the ratio of cows with a positive SI was higher in the longer CI group compared to the shorter group, suggesting that the selection for meat quality and quantity may affect the reproductive performances. In addition, the average value of SI was - 3.42 in the CI < 400 while + 5.79 in the CI > 400 although the values were not statistically significant. However, our results suggest that reproductive indices such as fertility and CI should be considered for sustainability in the Hanwoo breeding selection program.

• BMB Reports
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• v.54 no.3
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• pp.164-169
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• 2021

Neuronal growth regulator 1 (NEGR1) is a GPI-anchored membrane protein that is involved in neural cell adhesion and communication. Multiple genome wide association studies have found that NEGR1 is a generic risk factor for multiple human diseases, including obesity, autism, and depression. Recently, we reported that Negr1-/- mice showed a highly increased fat mass and affective behavior. In the present study, we identified Na/K-ATPase, beta1-subunit (ATP1B1) as an NEGR1 binding partner by yeast two-hybrid screening. NEGR1 and ATP1B1 were found to form a relatively stable complex in cells, at least partially co-localizing in membrane lipid rafts. We found that NEGR1 binds with ATP1B1 at its C-terminus, away from the binding site for the alpha subunit, and may contribute to intercellular interactions. Collectively, we report ATP1B1 as a novel NEGR1-interacting protein, which may help deciphering molecular networks underlying NEGR1-associated human diseases.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.9-9
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• 2021

Mutation breeding is useful for improving agronomic characteristics of various crops. In this study, we constructed soybean Mutant Diversity Pool (MDP) from 1,695 gamma-irradiated mutants through two selection phases over M1 to M12 generations; we selected 523 mutant lines exhibiting at least 30% superior agricultural characteristics, and, second, we eliminated redundant morphological phenotypes in the M12 generation. Finally, we constructed 208 MDP lines and investigated 11 agronomic traits. We then assessed the genetic diversity and inter-relationships of these MDP lines using target region amplification polymorphism (TRAP) markers. Among the different TRAP primer combinations, polymorphism levels and PIC values averaged 59.71% and 0.15, respectively. Dendrogram and population structure analyses divided the MDP lines into four major groups. According to an analysis of AMOVA, the percentage of inter-population variation among mutants was 11.320 (20.6%), whereas mutant inter-population variation ranged from 0.231 (0.4%) to 14.324 (26.1%). Overall, the genetic similarity of each cultivar and its mutants were higher than within other mutant populations. In an analysis of the genome-wide association study (GWAS) using based on the genotyping-by-sequencing (GBS), we detected 66 SNPs located on 13 different chromosomes were found to be highly associated with four agronomic traits: days of flowering (33 SNPs), flower color (16 SNPs), node number (6 SNPs), and seed coat color (11 SNPs). These results are consistent with those previously reported for other genetic resource populations, including natural accessions and recombinant inbred line. Our observations suggest that genomic changes in mutant individuals induced by gamma rays occurred at the same loci as those of natural soybean population. This study has demonstrated that the integration of GBS and GWAS can serve as a powerful complementary approach to gamma-ray mutation for the dissection of complex traits in soybean.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8051-8055
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• 2014

Background: A common genetic variant rs3757318, located in intron of C6orf97, was firstly identified to be associated with breast cancer (BC) risk by a genome-wide association (GWA) study. However, subsequent validation studies with different ethnicities have yielded conflicting results. Materials and Methods: We performed a meta-analysis to synthesize all available data for evaluating the precise effect of this variant on BC susceptibility. Results: A total of 8 articles containing 11 studies with 62,891 cases and 65,635 controls were included in this meta-analysis. When compared to the G allele, the rs3757318-A allele was significantly associated with BC risk with the pooled OR of 1.21 (95% CI=1.15 - 1.29, P<0.001) but with obvious between-study heterogeneity (P=0.040). Stratified analysis suggested that diversity of ethnicity along with control source may explain part of the heterogeneity. Similarly, significant associations were also identified in heterozygote, homozygote, dominant and recessive genetic models. Sensitivity and publication bias analyses indicated robust stability of our results. Conclusions: Our present meta-analysis demonstrated that the variant rs3757318 is associated with increased BC risk. Nevertheless, further studies are needed to clarify the underlying biological mechanisms.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.3
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• pp.320-333
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• 2019

Objective: The Shanghai Holstein cattle breed is susceptible to severe mastitis and other diseases due to the hot weather and long-term humidity in Shanghai, which is the main distribution centre for providing Holstein semen to various farms throughout China. Our objective was to determine the genetic mechanisms influencing economically important traits, especially diseases that have huge impact on the yield and quality of milk as well as reproduction. Methods: In our study, we detected the structural variations of 1,092 Shanghai Holstein cows by using next-generation sequencing. We used the DELLY software to identify deletions and insertions, cn.MOPS to identify copy-number variants (CNVs). Furthermore, we annotated these structural variations using different bioinformatics tools, such as gene ontology, cattle quantitative trait locus (QTL) database and ingenuity pathway analysis (IPA). Results: The average number of high-quality reads was 3,046,279. After filtering, a total of 16,831 deletions, 12,735 insertions and 490 CNVs were identified. The annotation results showed that these mapped genes were significantly enriched for specific biological functions, such as disease and reproduction. In addition, the enrichment results based on the cattle QTL database showed that the number of variants related to milk and reproduction was higher than the number of variants related to other traits. IPA core analysis found that the structural variations were related to reproduction, lipid metabolism, and inflammation. According to the functional analysis, structural variations were important factors affecting the variation of different traits in Shanghai Holstein cattle. Our results provide meaningful information about structural variations, which may be useful in future assessments of the associations between variations and important phenotypes in Shanghai Holstein cattle. Conclusion: Structural variations identified in this study were extremely different from those of previous studies. Many structural variations were found to be associated with mastitis and reproductive system diseases; these results are in accordance with the characteristics of the environment that Shanghai Holstein cattle experience.