Publications by authors named "Jeong-An Gim"

35 Publications

Draft genome of Semisulcospira libertina, a species of freshwater snail.

Genomics Inform 2021 Sep 30;19(3):e32. Epub 2021 Sep 30.

Department of Orthopaedic Surgery, Gyeongsang National University Hospital, Jinju 52727, Korea.

Semisulcospira libertina, a species of freshwater snail, is widespread in East Asia. It is important as a food source. Additionally, it is a vector of clonorchiasis, paragonimiasis, metagonimiasis, and other parasites. Although S. libertina has ecological, commercial, and clinical importance, its whole-genome has not been reported yet. Here, we revealed the genome of S. libertina through de novo assembly. We assembled the whole-genome of S. libertina and determined its transcriptome for the first time using Illumina NovaSeq 6000 platform. According to the k-mer analysis, the genome size of S. libertina was estimated to be 3.04 Gb. Using RepeatMasker, a total of 53.68% of repeats were identified in the genome assembly. Genome data of S. libertina reported in this study will be useful for identification and conservation of S. libertina in East Asia.
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http://dx.doi.org/10.5808/gi.21039DOI Listing
September 2021

LEFTY-PITX2 signaling pathway is critical for generation of mature and ventricular cardiac organoids in human pluripotent stem cell-derived cardiac mesoderm cells.

Biomaterials 2021 Sep 21;278:121133. Epub 2021 Sep 21.

Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, South Korea. Electronic address:

The generation of mature ventricular cardiomyocytes (CMs) resembling adult CMs from human pluripotent stem cells (hPSCs) is necessary for disease modeling and drug discovery. To investigate the effect of self-organizing capacity on the generation of mature cardiac organoids (COs), we generated cardiac mesoderm cell-derived COs (CMC-COs) and CM-derived COs (CM-COs) and evaluated COs. CMC-COs exhibited more organized sarcomere structures and mitochondria, well-arranged t-tubule structures, and evenly distributed intercalated discs. Increased expressions of ventricular CM, cardiac metabolic, t-tubule formation, K ion channel, and junctional markers were confirmed in CMC-COs. Mature ventricular-like function such as faster motion vector speed, decreased beats per min, increased peak-to-peak duration, and prolonged APD and APD were observed in CMC-COs. Transcriptional profiling revealed that extracellular matrix-integrin, focal adhesion, and LEFTY-PITX2 signaling pathways are upregulated in CMC-COs. LEFTY knockdown affected ECM-integrin-FA signaling pathways in CMC-COs. Here, we found that high self-organizing capacity of CMCs is critical for the generation of mature and ventricular COs. We also demonstrated that LEFTY-PITX2 signaling plays key roles for CM maturation and specification into ventricular-like CM subtype in CMC-COs. CMC-COs are an attractive resource for disease modeling and drug discovery.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121133DOI Listing
September 2021

Evaluation of the severity of nonalcoholic fatty liver disease through analysis of serum exosomal miRNA expression.

PLoS One 2021 6;16(8):e0255822. Epub 2021 Aug 6.

Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea.

Noninvasive techniques for evaluating the severity of nonalcoholic fatty liver disease (NAFLD) have shown limited diagnostic performance. MicroRNAs (miRNAs) are useful biomarkers for diagnosing and monitoring the progression and treatment response to several diseases. Here, we evaluated whether serum exosomal miRNAs could be used for the diagnosis and prognosis of NAFLD severity. Exosomal miRNAs were isolated from the sera of 41 patients with NAFLD (diagnosed using liver biopsy) for microarray profiling. The degree of NAFLD severity was determined using inflammation, steatosis, and ballooning scores and the NAFLD activity score (NAS). Correlations between miRNA expression, clinical and biochemical parameters, and mRNA expression were analyzed. Overall, 25, 11, 13, and 14 miRNAs correlated with the inflammation score, steatosis score, ballooning score, and NAS, respectively, with 33 significant correlations observed between 27 miRNAs and six clinical variables. Eight miRNAs (let-7b-5p, miR-378h, -1184, -3613-3p, -877-5p, -602, -133b, and 509-3p) showed anticorrelated patterns with the corresponding mRNA expression. In fibrosis, 52 and 30 interactions corresponding to high miRNA-low mRNA and low miRNA-high mRNA expression, respectively, were observed. The present results therefore suggest that serum exosomal miRNAs can be used to evaluate NAFLD severity and identify potential targets for NAFLD treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255822PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345824PMC
August 2021

Circulating miRNA is a useful diagnostic biomarker for nonalcoholic steatohepatitis in nonalcoholic fatty liver disease.

Sci Rep 2021 07 19;11(1):14639. Epub 2021 Jul 19.

Department of Internal Medicine, Division of Gastroenterology and Hepatology, Guro Hospital, Korea University College of Medicine, Korea University Medical Center, 97, Guro-Dong Gil, Guro-Dong, Guro-Ku, Seoul, 08308, Republic of Korea.

Nonalcoholic steatohepatitis (NASH) is considered as a progressive form of nonalcoholic fatty liver disease (NAFLD). To distinguish NASH from nonalcoholic fatty liver (NAFL), we evaluated the diagnostic value of circulating miRNAs. Small RNA sequencing was performed on 12 NAFL patients and 12 NASH patients, and the miRNA expression was compared. After selecting miRNAs for the diagnosis of NASH, we analyzed the diagnostic accuracy of each miRNA and the combination of miRNAs. External validation was performed using quantitative reverse transcription PCR. Among the 2,588 miRNAs, 26 miRNAs significantly increased in the NASH group than in the NAFL group. Among the 26 elevated miRNAs in the NASH group, 8 miRNAs were selected, and in silico analysis was performed. Only four miRNAs (miR-21-5p, miR-151a-3p, miR-192-5p, and miR-4449) showed significant area under the receiver operating characteristic curve (AUC) values for NASH diagnosis. The combination of the four miRNAs showed satisfactory diagnostic accuracy for NASH (AUC 0.875; 95% CI 0.676-0.973). External validation revealed similar diagnostic accuracy for NASH (AUC 0.874; 95% CI 0.724-0.960). NASH represents significantly distinct miRNA expression profile compared with NAFL. The combination of serum circulating miRNAs can be used as a novel biomarker for the NASH diagnosis in NAFLD.
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http://dx.doi.org/10.1038/s41598-021-94115-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289842PMC
July 2021

Intratumor Heterogeneity of Synchronous and Invasive Breast Carcinoma Revealed Using Multi-region Exome Sequencing.

Anticancer Res 2021 Aug;41(8):3779-3787

Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea

Background/aim: Intratumor heterogeneity (ITH), defined as a tumor composed of multiple subclones with different characteristics, is widely reported in invasive breast carcinoma (IBC) and ductal carcinoma in situ (DCIS). This study aimed to assess the extent of ITH in synchronous DCIS-IBC at the genetic level.

Materials And Methods: A total of 17 lesions from 5 patients were subjected to whole-exome sequencing. Nonsynonymous mutations and copy number aberrations were visualized to assess ITH.

Results: The most commonly mutated cancer-related genes in IBC and DCIS were RUNX1 (35.3%), PIK3CA (29.4%), and GATA3 (29.4%). There were no universally mutated cancer-related genes in all IBCs. All lesions harbored private mutations restricted to each lesion. Several DCIS lesions displayed a greater amount of genetic aberrations than the accompanying IBC, implying that a subset of DCIS was as advanced or more advanced than the synchronous IBC.

Conclusion: We herein demonstrated genetic ITH in DCIS lesions coexisting with IBC.
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http://dx.doi.org/10.21873/anticanres.15170DOI Listing
August 2021

RNA-sequencing identification and validation of genes differentially expressed in high-risk adenoma, advanced colorectal cancer, and normal controls.

Funct Integr Genomics 2021 Jul 17;21(3-4):513-521. Epub 2021 Jul 17.

Department of Pathology, College of Medicine, Korea University, Seoul, Republic of Korea.

Distinct gene expression patterns that occur during the adenoma-carcinoma sequence need to be determined to analyze the underlying mechanism in each step of colorectal cancer progression. Elucidation of biomarkers for colorectal polyps that harbor malignancy potential is important for prevention of colorectal cancer. Here, we use RNA sequencing to determine gene expression profile in patients with high-risk adenoma treated with endoscopic submucosal dissection by comparing with gene expression in patients with advanced colorectal cancer and normal controls. We collected 70 samples, which consisted of 27 colorectal polyps, 24 cancer tissues, and 19 normal colorectal mucosa. RNA sequencing was performed on an Illumina platform to select differentially expressed genes (DEGs) between colorectal polyps and cancer, polyps and controls, and cancer and normal controls. The Kyoto Gene and Genome Encyclopedia (KEGG) and gene ontology (GO) analysis, gene-concept network, GSEA, and a decision tree were used to evaluate the DEGs. We selected the most highly expressed genes in high-risk polyps and validated their expression using real-time PCR and immunohistochemistry. Compared to patients with colorectal cancer, 82 upregulated and 24 downregulated genes were detected in high-risk adenoma. In comparison with normal controls, 33 upregulated and 79 downregulated genes were found in high-risk adenoma. In total, six genes were retrieved as the highest and second highest expressed in advanced polyps and cancers among the three groups. Among the six genes, ANAX3 and CD44 expression in real-time PCR for validation was in good accordance with RNA sequencing. We identified differential expression of mRNAs among high-risk adenoma, advanced colorectal cancer, and normal controls, including that of CD44 and ANXA3, suggesting that this cluster of genes as a marker of high-risk colorectal adenoma.
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http://dx.doi.org/10.1007/s10142-021-00795-8DOI Listing
July 2021

DNA Methylation Profiling for the Diagnosis and Prognosis of Patients with Nontuberculous Lung Disease.

Curr Issues Mol Biol 2021 Jun 28;43(2):501-512. Epub 2021 Jun 28.

Medical Science Research Center, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea.

The incidence of nontuberculous (NTM) lung disease is rapidly increasing; however, its diagnosis and prognosis remain unclear while selecting patients who will respond to appropriate treatment. Differences in DNA methylation patterns between NTM patients with good or poor prognosis could provide important therapeutic targets. We used the Illumina MethylationEPIC (850k) DNA methylation microarray to determine the pattern between differentially methylated regions (DMRs) in NTM patients with good or poor prognosis ( = 4/group). Moreover, we merged and compared 20 healthy controls from previous Illumina Methylation450k DNA methylation microarray data. We selected and visualized the DMRs in the form of heatmaps, and enriched terms associated with these DMRs were identified by functional annotation with the "pathfinder" package. In total, 461 and 293 DMRs (|Log2 fold change| > 0.1 and < 0.03) were more methylated in patients with four poor and four good prognoses, respectively. Furthermore, 337 and 771 DMRs (|Log2 fold change| > 0.08 and < 0.001) were more methylated in eight NTM patients and 20 healthy controls, respectively. was significantly less methylated, whereas 1 and were more methylated in patients with poor prognosis (compared to those with good prognosis). , , and were the top three less-methylated genes in NTM patients (compared with the controls). The mTOR and Wnt signaling pathway-related genes were less methylated in patients with NTM. Collectively, genes related to Th1-cell differentiation, such as and , may be used as biomarkers for predicting the treatment response in patients with NTM lung disease.
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http://dx.doi.org/10.3390/cimb43020038DOI Listing
June 2021

Total Platelet Transcriptomics and Its Network Analysis by RNA-Seq and miRNA-Seq and PCA Application in Essential Thrombocythaemia.

Acta Haematol 2021 23;144(3):337-344. Epub 2020 Nov 23.

Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Republic of Korea,

Differentiating the aetiology of thrombocytosis is limited yet crucial in patients with essential thrombocythaemia (ET). MicroRNAs (miRNAs) regulate haematopoiesis and lineage commitment; aberrant expression of miRNAs plays an important role in myeloproliferative neoplasms. However, the miRNA profile has been poorly explored in ET patients compared to patients with reactive thrombocytosis (RT). A total of 9 samples, including 5 ET patient samples, 2 RT patient samples, and 2 healthy control samples, were analysed in this study. We produced 81.43 million reads from transcripts and 59.60 million reads from small RNAs. We generated a comprehensive miRNA-mRNA regulatory network and identified unique 14 miRNA expression patterns associated with ET. Among the 14 miRNAs, miR-1268a was downregulated in ET and showed an inverse correlation with its 8 putative target genes, including genes associated with thrombus formation and platelet activation (CDH6, EHD2, FUT1, KIF26A, LINC00346, PTPRN, SERF1A, and SLC6A9). Principal component analysis (PCA) showed ET and non-ET groups well clustered in space, suggesting each group had a distinctive expression pattern of mRNAs and miRNAs. These results suggest that the significant dysregulation of miR-1268a and its 8 target genes could be a unique expression of platelet mi-RNAs and miRNA/mRNA regulatory network in ET patients.
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http://dx.doi.org/10.1159/000510459DOI Listing
June 2021

Regular moderate aerobic exercise improves high-fat diet-induced nonalcoholic fatty liver disease via monoacylglycerol O-acyltransferase 1 pathway suppression.

J Sport Health Sci 2020 09 8;9(5):472-478. Epub 2018 Sep 8.

Division of Sport Science, Pusan National University, Busan 46241, Korea. Electronic address:

Purpose: Monoacylglycerol O-acyltransferase 1 (MGAT1) is reported to play a key role in the development of diet-induced nonalcoholic fatty liver disease (NAFLD). Thus, this study investigated the effect of exercise on suppression of the MGAT1 pathway in NAFLD tissue of high-fat diet (HFD)-induced obese rats.

Methods: Male Sprague-Dawley rats were fed an HFD containing 45% fat for 6 weeks. Upon confirmation that NAFLD had been induced in the obese animals, they were divided into HFD-fed groups provided with exercise (HFD + EXE) or without exercise (HFD) and a group given dietary adjustment (DA) only, for a further 6 weeks of intervention treatment. The 6-week regular moderate aerobic exercise consisted of an accommodation phase with increasing exercise. Lipid accumulation in the liver tissue was determined by Oil Red O staining. The MGAT1 and liver lipogenic gene mRNA levels were measured by qPCR, and their protein levels by western blot assay.

Results: Oil Red O staining showed that NAFLD was successfully induced by HFD-fed. The gene expression of MGAT1 was significantly lower in HFD + EXE than HFD. However, there was no significant difference between HFD + EXE and DA. The protein expression of MGAT1 was significantly lower in HFD + EXE than both HFD and DA. Messenger RNA and protein expression of other lipogenic genes were not different among groups. These data indicate that exercise suppresses MGAT1 pathway regardless of HFD feeding; in part, this effect could be greater than DA.

Conclusion: Our data suggest that exercise can improve NAFLD, which is probably due to suppression of MGAT1 pathway.
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http://dx.doi.org/10.1016/j.jshs.2018.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498633PMC
September 2020

A Machine Learning-Based Identification of Genes Affecting the Pharmacokinetics of Tacrolimus Using the DMET Plus Platform.

Int J Mol Sci 2020 Apr 4;21(7). Epub 2020 Apr 4.

Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 16229, Korea.

Tacrolimus is an immunosuppressive drug with a narrow therapeutic index and larger interindividual variability. We identified genetic variants to predict tacrolimus exposure in healthy Korean males using machine learning algorithms such as decision tree, random forest, and least absolute shrinkage and selection operator (LASSO) regression. (CYP3A5) and (CYP2A6) are single nucleotide polymorphisms (SNPs) that can affect exposure to tacrolimus. A decision tree, when coupled with random forest analysis, is an efficient tool for predicting the exposure to tacrolimus based on genotype. These tools are helpful to determine an individualized dose of tacrolimus.
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http://dx.doi.org/10.3390/ijms21072517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178269PMC
April 2020

Coxsackievirus B3 Infection of Human Neural Progenitor Cells Results in Distinct Expression Patterns of Innate Immune Genes.

Viruses 2020 03 17;12(3). Epub 2020 Mar 17.

Department of Biomedical Sciences, BK21 PLUS program, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea.

Coxsackievirus B3 (CVB3), a member of family, is an important human pathogen that causes a wide range of diseases, including myocarditis, pancreatitis, and meningitis. Although CVB3 has been well demonstrated to target murine neural progenitor cells (NPCs), gene expression profiles of CVB3-infected human NPCs (hNPCs) has not been fully explored. To characterize the molecular signatures and complexity of CVB3-mediated host cellular responses in hNPCs, we performed QuantSeq 3' mRNA sequencing. Increased expression levels of viral RNA sensors (, ) and interferon-stimulated genes, such as , , , , , , were detected in response to CVB3 infection, while expression level was significantly downregulated in hNPCs. Consistent with the gene expression profile, CVB3 infection led to enhanced secretion of inflammatory cytokines and chemokines, such as interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1). Furthermore, we show that type I interferon (IFN) treatment in hNPCs leads to significant attenuation of CVB3 RNA copy numbers, whereas, type II IFN (IFN-γ) treatment enhances CVB3 replication and upregulates suppressor of cytokine signaling 1/3 (SOCS) expression levels. Taken together, our results demonstrate the distinct molecular patterns of cellular responses to CVB3 infection in hNPCs and the pro-viral function of IFN-γ via the modulation of SOCS expression.
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http://dx.doi.org/10.3390/v12030325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150933PMC
March 2020

Association of metabolic and genetic heterogeneity in head and neck squamous cell carcinoma with prognostic implications: integration of FDG PET and genomic analysis.

EJNMMI Res 2019 Nov 21;9(1):97. Epub 2019 Nov 21.

Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.

Purpose: The linkage between the genetic and phenotypic heterogeneity of the tumor has not been thoroughly evaluated. Herein, we investigated how the genetic and metabolic heterogeneity features of the tumor are associated with each other in head and neck squamous cell carcinoma (HNSC). We further assessed the prognostic significance of those features.

Methods: The mutant-allele tumor heterogeneity (MATH) score (n = 508), a genetic heterogeneity feature, and tumor glycolysis feature (GlycoS) (n = 503) were obtained from the HNSC dataset in the cancer genome atlas (TCGA). We identified matching patients (n = 33) who underwent 18F-fluorodeoxyglucose positron emission tomography (FDG PET) from the cancer imaging archive (TCIA) and obtained the following information from the primary tumor: metabolic, metabolic-volumetric, and metabolic heterogeneity features. The association between the genetic and metabolic features and their prognostic values were assessed.

Results: Tumor metabolic heterogeneity and metabolic-volumetric features showed a mild degree of association with MATH (n = 25, ρ = 0.4~0.5, P < 0.05 for all features). The patients with higher FDG PET features and MATH died sooner. Combination of MATH and tumor metabolic heterogeneity features showed a better stratification of prognosis than MATH. Also, higher MATH and GlycoS were associated with significantly worse overall survival (n = 499, P = 0.002 and 0.0001 for MATH and GlycoS, respectively). Furthermore, both MATH and GlycoS independently predicted overall survival after adjusting for clinicopathologic features and the other (P = 0.015 and 0.006, respectively).

Conclusion: Both tumor metabolic heterogeneity and metabolic-volumetric features assessed by FDG PET showed a mild degree of association with genetic heterogeneity in HNSC. Both metabolic and genetic heterogeneity features were predictive of survival and there was an additive prognostic value when the metabolic and genetic heterogeneity features were combined. Also, MATH and GlycoS were independent prognostic factors in HNSC; they can be used for precise prognostication once validated.
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http://dx.doi.org/10.1186/s13550-019-0563-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872695PMC
November 2019

Association of metabolic and genetic heterogeneity in head and neck squamous cell carcinoma with prognostic implications: integration of FDG PET and genomic analysis.

EJNMMI Res 2019 Nov 21;9(1):97. Epub 2019 Nov 21.

Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.

Purpose: The linkage between the genetic and phenotypic heterogeneity of the tumor has not been thoroughly evaluated. Herein, we investigated how the genetic and metabolic heterogeneity features of the tumor are associated with each other in head and neck squamous cell carcinoma (HNSC). We further assessed the prognostic significance of those features.

Methods: The mutant-allele tumor heterogeneity (MATH) score (n = 508), a genetic heterogeneity feature, and tumor glycolysis feature (GlycoS) (n = 503) were obtained from the HNSC dataset in the cancer genome atlas (TCGA). We identified matching patients (n = 33) who underwent 18F-fluorodeoxyglucose positron emission tomography (FDG PET) from the cancer imaging archive (TCIA) and obtained the following information from the primary tumor: metabolic, metabolic-volumetric, and metabolic heterogeneity features. The association between the genetic and metabolic features and their prognostic values were assessed.

Results: Tumor metabolic heterogeneity and metabolic-volumetric features showed a mild degree of association with MATH (n = 25, ρ = 0.4~0.5, P < 0.05 for all features). The patients with higher FDG PET features and MATH died sooner. Combination of MATH and tumor metabolic heterogeneity features showed a better stratification of prognosis than MATH. Also, higher MATH and GlycoS were associated with significantly worse overall survival (n = 499, P = 0.002 and 0.0001 for MATH and GlycoS, respectively). Furthermore, both MATH and GlycoS independently predicted overall survival after adjusting for clinicopathologic features and the other (P = 0.015 and 0.006, respectively).

Conclusion: Both tumor metabolic heterogeneity and metabolic-volumetric features assessed by FDG PET showed a mild degree of association with genetic heterogeneity in HNSC. Both metabolic and genetic heterogeneity features were predictive of survival and there was an additive prognostic value when the metabolic and genetic heterogeneity features were combined. Also, MATH and GlycoS were independent prognostic factors in HNSC; they can be used for precise prognostication once validated.
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http://dx.doi.org/10.1186/s13550-019-0563-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872695PMC
November 2019

Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus).

Sci Rep 2018 12 24;8(1):18065. Epub 2018 Dec 24.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 46241, Republic of Korea.

Olive flounder (Paralichthys olivaceus) is one of economically valuable fish species in the East Asia. In comparison with its economic importance, available genomic information of the olive flounder is very limited. The mass mortality caused by variety of pathogens (virus, bacteria and parasites) is main problem in aquaculture industry, including in olive flounder culture. In this study, we carried out transcriptome analysis using the olive flounder gill tissues after infection of three types of pathogens (Virus; Viral hemorrhagic septicemia virus, Bacteria; Streptococcus parauberis, and Parasite; Miamiensis avidus), respectively. As a result, we identified total 12,415 differentially expressed genes (DEG) from viral infection, 1,754 from bacterial infection, and 795 from parasite infection, respectively. To investigate the effects of pathogenic infection on immune response, we analyzed Gene ontology (GO) enrichment analysis with DEGs and sorted immune-related GO terms per three pathogen groups. Especially, we verified various GO terms, and genes in these terms showed down-regulated expression pattern. In addition, we identified 67 common genes (10 up-regulated and 57 down-regulated) present in three pathogen infection groups. Our goals are to provide plenty of genomic knowledge about olive flounder transcripts for further research and report genes, which were changed in their expression after specific pathogen infection.
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http://dx.doi.org/10.1038/s41598-018-36342-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305387PMC
December 2018

Identification of transposable elements fused in the exonic region of the olive flounder genome.

Genes Genomics 2018 07 9;40(7):707-713. Epub 2018 Mar 9.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 46241, Republic of Korea.

Transposable elements (TEs) are mobile genetic sequences that comprise a large portion of vertebrate genomes. The olive flounder (Paralichthys olivaceus) is a valuable marine resource in East Asia. The scope of most genomic studies on the olive flounder is limited to its immunology as their focus is the prevention of mass mortality of this species. Thus, for a broader understanding of the species, its genomic information is consistently in demand. Transcripts sequences were acquired from transcriptome analysis using gill tissues of 12 olive flounders. Distribution of TEs inserted in exonic region of the olive flounder genome was analyzed using RepeatMasker ( http://www.repeatmasker.org/ ). We found 1140 TEs in the exonic region of the genome and long interspersed nuclear elements (LINEs) and long terminal repeats (LTRs) insertions occurred with forward orientation preferences. Transposons belonging to the hAt, Gypsy, and LINE 1 (L1) subfamilies were the most abundant DNA transposons, LTRs, and long interspersed elements (LINEs), respectively. Finally, we carried out a gene ontology analysis to determine the function of TE-fused genes. These results provide some genomic information about TEs that is useful for future research on changes in properties and functions of genes by TEs in the olive flounder genome.
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http://dx.doi.org/10.1007/s13258-018-0676-2DOI Listing
July 2018

Ty3/Gypsy retrotransposons in the Pacific abalone Haliotis discus hannai: characterization and use for species identification in the genus Haliotis.

Genes Genomics 2018 02 13;40(2):177-187. Epub 2017 Oct 13.

Institute of Biotechnology and Bioscience, Kangwon National University, Chuncheon, 24341, Republic of Korea.

Transposable elements are highly abundant elements that are present in all eukaryotic species. Here, we present a molecular description of abalone retrotransposon (Abret) elements. The genome of Haliotis discus hannai contains 130 Abret elements which were all Ty3/Gypsy retrotransposons. The Ty1/Copia elements were absent in the H. discus hannai genome. Most of the elements were not complete due to sequence truncation or coding region decay. However, three elements Abret-296, Abret-935, and Abret-3259 had most of the canonical features of LTR (long terminal repeat)-retrotransposons. There were several reading frame shifts in Abret-935 and Abret-3259 elements. Surprisingly, phylogenetic analysis indicated that all of the elements belonged to the Osvaldo lineage. The sequence divergence between LTRs revealed that the Abret elements were mostly active within 2 million years ago. Abret elements were used as molecular markers in SSAP analyses, which allowed clear distinction of different species in the genus Haliotis. The polymorphic markers were converted into SCAR markers for use in species identification by simple PCR in the Haliotis genus.
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http://dx.doi.org/10.1007/s13258-017-0619-3DOI Listing
February 2018

Current Challenges of Infection and Effective Molecular, Cellular, and Environmental Control Methods in Aquaculture.

Mol Cells 2018 Jun 10;41(6):495-505. Epub 2018 May 10.

Institute of Systems Biology, Pusan National University, Busan 46241, Korea.

Several bacterial etiological agents of streptococcal disease have been associated with fish mortality and serious global economic loss. Bacterial identification based on biochemical, molecular, and phenotypic methods has been routinely used, along with assessment of morphological analyses. Among these, the molecular method of 16S rRNA sequencing is reliable, but presently, advanced genomics are preferred over other traditional identification methodologies. This review highlights the geographical variation in strains, their relatedness, as well as the complexity of diagnosis, pathogenesis, and various control methods of streptococcal infections. Several limitations, from diagnosis to control, have been reported, which make prevention and containment of streptococcal disease difficult. In this review, we discuss the challenges in diagnosis, pathogenesis, and control methods and suggest appropriate molecular (comparative genomics), cellular, and environmental solutions from among the best available possibilities.
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http://dx.doi.org/10.14348/molcells.2018.2154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030242PMC
June 2018

Complete mitochondrial genome of the freshwater bryozoan (Phylactolaemata: Plumatellida) assembled from next-generation sequencing data.

Mitochondrial DNA B Resour 2018 Mar 15;3(1):373-374. Epub 2018 Mar 15.

Department of Bioscience, Aarhus University, Silkeborg, Denmark.

The complete mitochondrial genome of the freshwater bryozoan was sequenced. The circular mitochondrial genome is 17,539 bp and consists of 13 protein-coding, two ribosomal RNA, and 22 transfer RNA genes (GenBank accession no. MG546680). The Bayesian comparative analysis of molecular evolution rates revealed no acceleration of the mitochondrial DNA (mtDNA) evolution of . Results of maximum likelihood analysis showed that this species clustered with other species of the phylum Bryozoa.
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http://dx.doi.org/10.1080/23802359.2018.1450657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799736PMC
March 2018

Effects of regular-moderate exercise on high-fat diet-induced intramyocellular lipid accumulation in the soleus muscle of Sprague-Dawley rats.

J Exerc Rehabil 2018 Feb 26;14(1):32-38. Epub 2018 Feb 26.

Division of Sport Science, Pusan National University, Busan, Korea.

Previously, we monitored the expression level of the pro-apoptotic proteins caspase-3 and cleaved poly-ADP-ribose polymerase in the skeletal muscle of high-fat diet-induced obese rats in order to assess muscle damage. In this study, we analyzed whether exercise or dietary adjustment was more effective at preventing high-fat diet-induced muscle damage. High-fat diet-induced obese rats were divided into three groups: the high-fat diet (HFD), the combined high-fat diet and exercise (HFD+EXE), and the dietary adjustment (DA) groups. For 6 weeks, the HFD+EXE group was subjected to exercise on an animal treadmill. Capsase-3 protein was quantified, and histopathology of the soleus muscle was performed. Both the HFD+EXE and DA interventions resulted in a reduction of lipid accumulation in the soleus muscle, and nucleus infiltration was significantly lower in the DA group. The inflammatory response, caspase-3 level, and relative muscle weight were significantly higher in the HFD+EXE group compared to the HFD group. An increase in intramyocellular lipids in the soleus muscle by obesity and exercise stimulated apoptosis. When the rats exercised, muscle growth was normal and unrelated to the effects of lipid accumulation. These data indicate that exercise was more effective than dietary adjustment in reducing lipid accumulation and increasing muscle metabolism.
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http://dx.doi.org/10.12965/jer.1835166.583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833965PMC
February 2018

The involvement of serum exosomal miR-500-3p and miR-770-3p in aging: modulation by calorie restriction.

Oncotarget 2018 Jan 24;9(5):5578-5587. Epub 2017 Dec 24.

Molecular Inflammation Research Center for Aging Intervention, College of Pharmacy, Pusan National University, Busan, Republic of Korea.

Recent studies have shown a role for miRNAs in aging and age-related diseases, and the modulation of miRNA expression by diet attracts attention as a new therapeutic strategy. Here, we focused on identifying specific exosomal miRNAs derived from serum of aged rats and the effect of short-term calorie restriction (CR) on their expression. Exosomes from serum of young (7-month), old (22-month), and old-CR Sprague Dawley rats were isolated and characterized by transmission electron microscopy analyses, dynamic light scattering measurements, and Western blotting. A total of 12 significantly expressed miRNAs in serum exosomes of young and old rats were identified by next generation sequencing. After analysis of qRT-PCR, we found that miR-500-3p and miR-770-3p expression was significantly upregulated by aging and downregulated by CR. Furthermore, receiver operating characteristic (ROC) curve revealed that the selected miRNAs represented high accuracy in discriminating old rats from young rats. Finally, PANTHER analysis predicted selected miRNAs targets genes involved in Wnt/chemokines and cytokines -related inflammatory signaling pathway and function as transcription factor. In conclusion, our results suggest that the expression of serum exosomal miR-500-3p and miR-770-3p was significantly increased with aging, whereas these were decreased by CR, and age-/CR-modulated exosomal miR-500-3p and miR-770-3p could potentially be used as informative biomarkers candidates for aging.
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http://dx.doi.org/10.18632/oncotarget.23651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814159PMC
January 2018

Identification and Expression Analyses of Equine Endogenous Retroviruses in Horses.

Mol Cells 2017 Oct 17;40(10):796-804. Epub 2017 Oct 17.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea.

Endogenous retroviruses (ERVs) have been integrated into vertebrate genomes and have momentously affected host organisms. Horses () have been domesticated and selected for elite racing ability over centuries. ERVs played an important role in the evolutionary diversification of the horse genome. In the present study, we identified six equine ERV families (EqERVs-E1, I1, M2, P1, S1, and Y4), their full-length viral open reading frames (ORFs), and elucidated their phylogenetic relationships. The divergence time of EqERV families assuming an evolutionary rate of 0.2%/Myr indicated that EqERV-S3 (75.4 million years ago; mya) on chromosome 10 is an old EqERV family and EqERV-P5 (1.2 Mya) on chromosome 12 is a young member. During the evolutionary diversification of horses, the EqERV-I family diverged 1.7 Mya to 38.7 Mya. Reverse transcription quantitative real-time PCR (RT-qPCR) amplification of EqERV genes showed greater expression in the cerebellum of the Jeju horse than the Thoroughbred horse. These results could contribute further dynamic studies for horse genome in relation to EqERV gene function.
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http://dx.doi.org/10.14348/molcells.2017.0141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682256PMC
October 2017

Identification and Expression of Equine MER-Derived miRNAs.

Mol Cells 2017 Apr 21;40(4):262-270. Epub 2017 Mar 21.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea.

MicroRNAs (miRNAs) are single-stranded, small RNAs (21-23 nucleotides) that function in gene silencing and translational inhibition via the RNA interference mechanism. Most miRNAs originate from host genomic regions, such as intergenic regions, introns, exons, and transposable elements (TEs). Here, we focused on the palindromic structure of medium reiteration frequencies (MERs), which are similar to precursor miRNAs. Five MER consensus sequences (MER5A1, MER53, MER81, MER91C, and MER117) were matched with paralogous transcripts predicted to be precursor miRNAs in the horse genome (equCab2) and located in either intergenic regions or introns. The MER5A1, MER53, and MER91C sequences obtained from RepeatMasker were matched with the eca-miR-544b, eca-miR-1302, and eca-miR-652 precursor sequences derived from Ensembl transcript database, respectively. Each precursor form was anticipated to yield two mature forms, and we confirmed miRNA expression in six different tissues (cerebrum, cerebellum, lung, spleen, adrenal gland, and duodenum) of one thorough-bred horse. MER5A1-derived miRNAs generally showed significantly higher expression in the lung than in other tissues. MER91C-derived miRNA-5p also showed significantly higher expression in the duodenum than in other tissues (cerebellum, lung, spleen, and adrenal gland). The MER117-overlapped expressed sequence tag generated polycistronic miRNAs, which showed higher expression in the duodenum than other tissues. These data indicate that horse MER transposons encode miR-NAs that are expressed in several tissues and are thought to have biological functions.
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http://dx.doi.org/10.14348/molcells.2017.2295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424272PMC
April 2017

Integrated late onset Alzheimer's disease (LOAD) susceptibility genes: Cholesterol metabolism and trafficking perspectives.

Gene 2017 Jan 20;597:10-16. Epub 2016 Oct 20.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea; Genetic Engineering Institute, Pusan National University, Busan 46241, Republic of Korea. Electronic address:

Late onset Alzheimer's disease (LOAD) is the most common type of dementia and is characterized by decreased amyloid-β (Aβ) clearance from the brain. Cholesterol regulates the production and clearance of Aβ. Genome-wide association study (GWAS) suggests that at least 20 genes are associated with LOAD. The genes APOE, CLU, SORL1, PICALM, and BIN1 have a relatively high LOAD susceptibility. Additional experimental and bioinformatic approaches to integrate data from genetics, epigenetics, and molecular networks may further increase our understanding of LOAD in relation to cholesterol metabolism and trafficking.
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http://dx.doi.org/10.1016/j.gene.2016.10.022DOI Listing
January 2017

Gene structure variation in segmental duplication block C of human chromosome 7q 11.23 during primate evolution.

Gene 2015 Dec 18;573(2):285-95. Epub 2015 Jul 18.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea. Electronic address:

Segmental duplication, or low-copy repeat (LCR) event, occurs during primate evolution and is an important source of genomic diversity, including gain or loss of gene function. The human chromosome 7q 11.23 is related to the William-Beuren syndrome and contains large region-specific LCRs composed of blocks A, B, and C that have different copy numbers in humans and different primates. We analyzed the structure of POM121, NSUN5, FKBP6, and TRIM50 genes in the LCRs of block C. Based on computational analysis, POM121B created by a segmental duplication acquired a new exonic region, whereas NSUN5B (NSUN5C) showed structural variation by integration of HERV-K LTR after duplication from the original NSUN5 gene. The TRIM50 gene originally consists of seven exons, whereas the duplicated TRIM73 and TRIM74 genes present five exons because of homologous recombination-mediated deletion. In addition, independent duplication events of the FKBP6 gene generated two pseudogenes at different genomic locations. In summary, these clustered genes are created by segmental duplication, indicating that they show dynamic evolutionary events, leading to structure variation in the primate genome.
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http://dx.doi.org/10.1016/j.gene.2015.07.060DOI Listing
December 2015

Identification and expression analysis of human endogenous retrovirus Y (HERV-Y) in various human tissues.

Arch Virol 2015 Sep 20;160(9):2161-8. Epub 2015 Jun 20.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 609-735, Republic of Korea.

Human endogenous retroviruses (HERVs) account for approximately 8% of the human genome. To date, several HERV families have been identified in the human genome, with some being valid biomarkers for specific disease states. In this study, we have identified three HERV-Y elements in the human genome and characterized their structure and expression in various human tissues. New HERV-Y elements (HERV-Y101, HERV-Y102, and HERV-Y103) were detected on human chromosomes 8 and 13. In a pol-based phylogenetic tree, HERV-Y elements were closely grouped with HERV-I, -T, -E, and -R. The HERV-Y pol gene was expressed ubiquitously in all examined tissues, and it was dominantly expressed in the pons among the 12 different brain regions investigated. These results will allow future studies to elucidate the potential functional roles of HERVs in the brain and other tissues.
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http://dx.doi.org/10.1007/s00705-015-2486-zDOI Listing
September 2015

Genome-Wide Identification and Classification of MicroRNAs Derived from Repetitive Elements.

Genomics Inform 2014 Dec 31;12(4):261-7. Epub 2014 Dec 31.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Korea.

MicroRNAs (miRNAs) are known for their role in mRNA silencing via interference pathways. Repetitive elements (REs) share several characteristics with endogenous precursor miRNAs. In this study, 406 previously identified and 1,494 novel RE-derived miRNAs were sorted from the GENCODE v.19 database using the RepeatMasker program. They were divided into six major types, based on their genomic structure. More novel RE-derived miRNAs were confirmed than identified as RE-derived miRNAs. In conclusion, many miRNAs have not yet been identified, most of which are derived from REs.
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http://dx.doi.org/10.5808/GI.2014.12.4.261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330264PMC
December 2014

Genome-wide analysis of DNA methylation before-and after exercise in the thoroughbred horse with MeDIP-Seq.

Mol Cells 2015 Mar 30;38(3):210-20. Epub 2015 Jan 30.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Korea.

Athletic performance is an important criteria used for the selection of superior horses. However, little is known about exercise-related epigenetic processes in the horse. DNA methylation is a key mechanism for regulating gene expression in response to environmental changes. We carried out comparative genomic analysis of genome-wide DNA methylation profiles in the blood samples of two different thoroughbred horses before and after exercise by methylated-DNA immunoprecipitation sequencing (MeDIP-Seq). Differentially methylated regions (DMRs) in the pre-and post-exercise blood samples of superior and inferior horses were identified. Exercise altered the methylation patterns. After 30 min of exercise, 596 genes were hypomethylated and 715 genes were hypermethylated in the superior horse, whereas in the inferior horse, 868 genes were hypomethylated and 794 genes were hypermethylated. These genes were analyzed based on gene ontology (GO) annotations and the exercise-related pathway patterns in the two horses were compared. After exercise, gene regions related to cell division and adhesion were hypermethylated in the superior horse, whereas regions related to cell signaling and transport were hypermethylated in the inferior horse. Analysis of the distribution of methylated CpG islands confirmed the hypomethylation in the gene-body methylation regions after exercise. The methylation patterns of transposable elements also changed after exercise. Long interspersed nuclear elements (LINEs) showed abundance of DMRs. Collectively, our results serve as a basis to study exercise-based reprogramming of epigenetic traits.
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http://dx.doi.org/10.14348/molcells.2015.2138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363720PMC
March 2015

HEpD: a database describing epigenetic differences between Thoroughbred and Jeju horses.

Gene 2015 Apr 28;560(1):83-8. Epub 2015 Jan 28.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea; Genetic Engineering Institute, Pusan National University, Busan 609-735, Republic of Korea. Electronic address:

With the advent of next-generation sequencing technology, genome-wide maps of DNA methylation are now available. The Thoroughbred horse is bred for racing, while the Jeju horse is a traditional Korean horse bred for racing or food. The methylation profiles of equine organs may provide genomic clues underlying their athletic traits. We have developed a database to elucidate genome-wide DNA methylation patterns of the cerebrum, lung, heart, and skeletal muscle from Thoroughbred and Jeju horses. Using MeDIP-Seq, our database provides information regarding significantly enriched methylated regions beyond a threshold, methylation density of a specific region, and differentially methylated regions (DMRs) for tissues from two equine breeds. It provided methylation patterns at 784 gene regions in the equine genome. This database can potentially help researchers identify DMRs in the tissues of these horse species and investigate the differences between the Thoroughbred and Jeju horse breeds.
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http://dx.doi.org/10.1016/j.gene.2015.01.047DOI Listing
April 2015

MicroRNA-124 regulates glucocorticoid sensitivity by targeting phosphodiesterase 4B in diffuse large B cell lymphoma.

Gene 2015 Mar 7;558(1):173-80. Epub 2015 Jan 7.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea. Electronic address:

Glucocorticoids (GCs) are chemotherapeutic drugs commonly used to treat hematological malignancies. However, a significant fraction of patients develop resistance to GCs during treatment. A better insight into how GC resistance develops is therefore needed. It was previously shown that cyclic AMP (cAMP) induces sensitivity to GCs by inhibiting the AKT/mTOR/MCL1 signaling, while high levels of phosphodiesterase 4B (PDE4B) reverse the effect of cAMP on GC responses in B-cell lymphoma. Here, we show that miR-124 influences GC-induced apoptosis by directly targeting PDE4B. Stable expression of miR-124 in diffuse large B cell lymphoma (DLBCL) cell lines diminished PDE4B expression. This was associated with increased cAMP levels, inhibition of the AKT/mTOR/MCL1 survival pathway, upregulation of GRα expression, and improved sensitivity to GCs in the presence of forskolin, an activator of adenylyl cyclase. Interestingly, miR-124 did not affect GC sensitivity in the absence of forskolin, indicating that the effect of this miRNA is accomplished via downregulation of PDE4B expression. Further, restoration of PDE4B expression in miR-124 cells rescued the phenotypic effect of this miRNA, demonstrating the critical role of PDE4B in miR-124-mediated regulation of the GC response. Our study supports the notion that miR-124 could be an attractive therapeutic target for overcoming GC resistance in DLBCL.
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http://dx.doi.org/10.1016/j.gene.2015.01.001DOI Listing
March 2015

Genome-wide analysis of DNA methylation patterns in horse.

BMC Genomics 2014 Jul 15;15:598. Epub 2014 Jul 15.

Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.

Background: DNA methylation is an epigenetic regulatory mechanism that plays an essential role in mediating biological processes and determining phenotypic plasticity in organisms. Although the horse reference genome and whole transcriptome data are publically available the global DNA methylation data are yet to be known.

Results: We report the first genome-wide DNA methylation characteristics data from skeletal muscle, heart, lung, and cerebrum tissues of thoroughbred (TH) and Jeju (JH) horses, an indigenous Korea breed, respectively by methyl-DNA immunoprecipitation sequencing. The analysis of the DNA methylation patterns indicated that the average methylation density was the lowest in the promoter region, while the density in the coding DNA sequence region was the highest. Among repeat elements, a relatively high density of methylation was observed in long interspersed nuclear elements compared to short interspersed nuclear elements or long terminal repeat elements. We also successfully identified differential methylated regions through a comparative analysis of corresponding tissues from TH and JH, indicating that the gene body regions showed a high methylation density.

Conclusions: We provide report the first DNA methylation landscape and differentially methylated genomic regions (DMRs) of thoroughbred and Jeju horses, providing comprehensive DMRs maps of the DNA methylome. These data are invaluable resource to better understanding of epigenetics in the horse providing information for the further biological function analyses.
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http://dx.doi.org/10.1186/1471-2164-15-598DOI Listing
July 2014
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