• Korean Circulation Journal
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• v.54 no.9
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• pp.577-586
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• 2024

Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20-25% of untreated children with KD and 3-5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Results: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25-9.98; p=0.00204-1.96×10^-6), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. Conclusions: A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.7
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• pp.926-935
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• 2015

The efficiency of genome-wide association analysis (GWAS) depends on power of detection for quantitative trait loci (QTL) and precision for QTL mapping. In this study, three different strategies for GWAS were applied to detect QTL for carcass quality traits in the Korean cattle, Hanwoo; a linkage disequilibrium single locus regression method (LDRM), a combined linkage and linkage disequilibrium analysis (LDLA) and a $BayesC{\pi}$ approach. The phenotypes of 486 steers were collected for weaning weight (WWT), yearling weight (YWT), carcass weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area, and marbling score (Marb). Also the genotype data for the steers and their sires were scored with the Illumina bovine 50K single nucleotide polymorphism (SNP) chips. For the two former GWAS methods, threshold values were set at false discovery rate <0.01 on a chromosome-wide level, while a cut-off threshold value was set in the latter model, such that the top five windows, each of which comprised 10 adjacent SNPs, were chosen with significant variation for the phenotype. Four major additive QTL from these three methods had high concordance found in 64.1 to 64.9Mb for Bos taurus autosome (BTA) 7 for WWT, 24.3 to 25.4Mb for BTA14 for CWT, 0.5 to 1.5Mb for BTA6 for BFT and 26.3 to 33.4Mb for BTA29 for BFT. Several candidate genes (i.e. glutamate receptor, ionotropic, ampa 1 [GRIA1], family with sequence similarity 110, member B [FAM110B], and thymocyte selection-associated high mobility group box [TOX]) may be identified close to these QTL. Our result suggests that the use of different linkage disequilibrium mapping approaches can provide more reliable chromosome regions to further pinpoint DNA makers or causative genes in these regions.

• Interdisciplinary Bio Central
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• v.6 no.4
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• pp.2.1-2.7
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• 2014

Sexual dimorphism in intelligence suggests that this phenotype is a sexually selected trait. This view is supported by an overrepresentation (compared to the autosomal genome) of genes affecting cognition on the X chromosome. The aim of this study is to test the hypothesis that sexual selection can explain sex and country-level differences in performance on tests of fluid intelligence. Nationally representative samples from N = 44 countries were obtained from the Programme for International Student Assessment (PISA) Creative Problem Solving (CPS), which evaluates the core of intelligence, that is novel problem solving ability. Sexual selection has the double effect of increasing the prevalence of a favored phenotype and reducing genetic variation in sexually selected traits. Matching these predictions from evolutionary theory, the average country fluid intelligence is positively correlated to sexual dimorphism after partialling out per capita GDP and the latter in turn is inversely correlated to variance in intelligence scores within populations. Males have a higher variance than females but there is a negative correlation between male-female difference in variance and sexual dimorphism in intelligence, suggesting that selection reduces variance more in the selected sex. Average country male height is negatively correlated to sexual dimorphism in intelligence, a fact that supports the notion of a trade-off between physical and intellectual competition in the context of access to females. The results of this study, if replicated, imply that genome-wide association studies of cognition may benefit from a focus on sex chromosomes, which so far have been neglected. Another implication of this study is that intelligence has continued to evolve after different human populations migrated out of Africa and possibly up to the 19th century, as suggested by the substantial variability in sex differences even between neighbouring countries.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.106-106
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• 2017

The soybean [Glycine max (L.) Merr.] is one of the most important crop resources worldwide as food and forage. It is also important and valuable that to hold crop resources to have high genetic diversities. Recently, a core collection has been constructed in many plants to preserve the genetic resources of various plants. A core collection is small population to represent the genetic diversity of the total collection, and is of strategic importance as they allow the use of a small part of a germplasm collection that is representative of the total collection. Here, we developed the core collection consisting of 816 accessions by using approximately 180,000 (180K) single nucleotide polymorphisms (SNPs) developed in previous study. In addition, we performed genetic diversity and population structure analysis to construct the core collection from entire 4,392 collections. there were excluded sample call rates less than 93% and duplicated samples more than 99.9% according to genotype analysis using 180K SNPs from entire collections. Furthermore, we were also excluded natural hybrid resources which Glycine max and Glycine soja are mixed in half through population structure analysis. As a result, we are constructed the core collection of genetic diversity that reflects 99% of the entire collections, including 430 cultivated soybeans (Glycine max) and 386 wild soybeans (Glycine soja). The core collection developed in this study should be to provide useful materials for both soybean breeding programs and genome-wide association studies.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.19-19
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• 2019

유전체 전장 연관분석 (GWAS)은 단일염기다형성(SNP)의 유전자형과 표현형 간의 통계적인 연관성을 분석함으로써 품종 선발용 SNP Marker 개발에 응용되고 있다. 본 연구에서는 Tano Red와 Ruby seedless 교배실생 278 계통을 대상으로 여러 과실 특성에 따른 관련 SNP를 동정함으로써 육종 선발에 필요한 DNA marker 개발에 필요한 기초 유전 자료를 얻고자 하였다. 한 계통 당 5~10개의 포도알을 선택하여 과립중, 과육탄성, 과피탄성, 과육경도, 과피경도, 과립당 종자갯수, 과립당 종자무게 및 인장강도를 측정하였다. 각 개체는 Genotyping by sequencing (GBS) 방법으로 Sequencing하여 Reference genome (Vitis vinifera PN40024 12X v2.)과 mapping 하였다. MAF (Minor allele frequency) >5%, Missing Data <30% 의 조건을 가진 SNPs 만 1차 선발하여 TASSEL과 GAPIT 프로그램으로 GWAS 분석을 하였다. Manhattan plot 결과 과립중 형질에서는 33개, 과립당 종자무게 25개와 인장강도에서는 20개의 통계학적으로 유의한 SNPs 가 선발되었고, 특이적으로 이들 모두 18번 염색체에서 발견되었다. 그러나 나머지 형질에서는 유의한 차이를 보이는 SNPs를 선발하지 못하였다. 과실의 인장강도는 수확 후 저장성과 유통과정에 영향을 미치기 때문에 Marker 개발을 통한 품종선별이 중요하다. 향후 이러한 특성과 본 연구를 통해 동정된 SNPs 의 상관관계를 구체적으로 연구하여 Marker 개발에 활용하고자 한다.

• Genomics & Informatics
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• v.21 no.3
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• pp.31.1-31.8
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• 2023

Multiple myeloma (MM) is a hematological malignancy. It is widely believed that genetic factors play a significant role in the development of MM, as investigated in numerous studies. However, the application of genomic information for clinical purposes, including diagnostic and prognostic biomarkers, remains largely confined to research. In this study, we utilized genetic information from the Genomic-Driven Clinical Implementation for Multiple Myeloma database, which is dedicated to clinical trial studies on MM. This genetic information was sourced from the genome-wide association studies catalog database. We prioritized genes with the potential to cause MM based on established annotations, as well as biological risk genes for MM, as potential drug target candidates. The DrugBank database was employed to identify drug candidates targeting these genes. Our research led to the discovery of 14 MM biological risk genes and the identification of 10 drugs that target three of these genes. Notably, only one of these 10 drugs, panobinostat, has been approved for use in MM. The two most promising genes, calcium signal-modulating cyclophilin ligand (CAMLG) and histone deacetylase 2 (HDAC2), were targeted by four drugs (cyclosporine, belinostat, vorinostat, and romidepsin), all of which have clinical evidence supporting their use in the treatment of MM. Interestingly, five of the 10 drugs have been approved for other indications than MM, but they may also be effective in treating MM. Therefore, this study aimed to clarify the genomic variants involved in the pathogenesis of MM and highlight the potential benefits of these genomic variants in drug discovery.

• Animal Bioscience
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• v.37 no.8
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• pp.1317-1332
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• 2024

Objective: Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Methods: Herein, we constructed the high-fat diet-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer and super enhancer target genes and conservative genes involved in metabolic processes. Results: In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange) ≥1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange)≤-1) (PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. Conclusion: Together, our studies have identified potential therapeutic biomarkers of PCK1 and elucidated novel insights into the pathogenesis of FLHS, especially for the epigenetic perspective.

• Nutrition Research and Practice
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• v.18 no.5
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• pp.721-745
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• 2024

BACKGROUND/OBJECTIVES: The high consumption of purine-rich meat is associated with hyperuricemia. However, there is limited evidence linking the consumption of red and processed meat to the genetic risk of hyperuricemia. We investigated the relationship between various combinations of red and processed meat consumption and the polygenic risk scores (PRSs) and the incidence of hyperuricemia in middle-aged Koreans. SUBJECTS/METHODS: We analyzed the data from 44,053 participants aged ≥40 years sourced from the Health Examinees (HEXA) cohort of the Korean Genome and Epidemiology Study (KoGES). Information regarding red and processed meat intake was obtained using a semiquantitative food frequency questionnaire (SQ-FFQ). We identified 69 independent single-nucleotide polymorphisms (SNPs) at uric acid-related loci using genome-wide association studies (GWASs) and clumping analyses. The individual PRS, which is the weighted sum of the effect size of each allele at the SNP, was calculated. We used multivariable Cox proportional hazards models adjusted for covariates to determine the relationship between red and processed meat intake and the PRS in the incidence of hyperuricemia. RESULTS: During an average follow-up period of 5 years, 2,556 patients with hyperuricemia were identified. For both men and women, the group with the highest red and processed meat intake and the highest PRS was positively associated with the development of hyperuricemia when compared with the group with the lowest red and processed meat intake and the lowest PRS (hazard ratio [HR], 2.72; 95% confidence interval [CI], 2.10-3.53; P < 0.0001; HR, 3.28; 95% CI, 2.45-4.40; P < 0.0001). CONCLUSION: Individuals at a high genetic risk for uric acid levels should moderate their consumption of red and processed meat to prevent hyperuricemia.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.9
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• pp.1235-1243
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• 2015

The goat Capra hircus is one of several economically important livestock in China. Advances in molecular genetics have led to the identification of several single nucleotide variation markers associated with genes affecting economic traits. Validation of single nucleotide variations in a whole-transcriptome sequencing is critical for understanding the information of molecular genetics. In this paper, we aim to develop a large amount of convinced single nucleotide polymorphisms (SNPs) for Cashmere goat through transcriptome sequencing. In this study, the transcriptomes of Cashmere goat skin at four stages were measured using RNA-sequencing and 90% to 92% unique-mapped-reads were obtained from total-mapped-reads. A total of 56,231 putative SNPs distributed among 10,057 genes were identified. The average minor allele frequency of total SNPs was 18%. GO and KEGG pathway analysis were conducted to analyze the genes containing SNPs. Our follow up biological validation revealed that 64% of SNPs were true SNPs. Our results show that RNA-sequencing is a fast and efficient method for identification of a large number of SNPs. This work provides significant genetic resources for further research on Cashmere goats, especially for the high density linkage map construction and genome-wide association studies.

• IMMUNE NETWORK
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• v.14 no.2
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• pp.67-72
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• 2014

The herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF), and therefore it is also known as TNFRSF14 or CD270 (1,2). In recent years, we have focused on understanding HVEM function in the mucosa of the intestine, particularly on the role of HVEM in colitis pathogenesis, host defense and regulation of the microbiota (2-4). HVEM is an unusual TNF receptor because of its high expression levels in the gut epithelium, its capacity to bind ligands that are not members of the TNF super family, including immunoglobulin (Ig) superfamily members BTLA and CD160, and its bi-directional functionality, acting as a signaling receptor or as a ligand for the receptor BTLA. Clinically, Hvem recently was reported as an inflammatory bowel disease (IBD) risk gene as a result of genome wide association studies (5,6). This suggests HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense and the microbiota. Consistent with this, using mouse models, we have revealed how HVEM is involved in colitis pathogenesis, mucosal host defense and epithelial immunity (3,7). Although further studies are needed, our results provide the fundamental basis for understanding why Hvem is an IBD risk gene, and they confirm that HVEM is a mucosal gatekeeper with multiple regulatory functions in the mucosa.