• Journal of Genetic Medicine
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• 제3권1호
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• pp.15-19
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• 1999

We have investigated the genetic variation in the human apo B mRNA editing protein (apobec-1) gene. Exon 3 of the apobec-1 gene was amplified by polymerase chain reaction. After detection of an additional band by single strand conformational polymorphism (SSCP) analysis, sequencing of the SSCP-shift sample revealed a single-base mutation. The mutation was a CGG transversion at codon 80 resulting in a lleRMet substitution. This substitution was confirmed by restriction fragment length polymorphism analysis since a Pvull site is abolished by the substitution. Population and family studies confirmed that the inheritance of the genotypes for apobec-1 gene polymorphism is controlled by two codominant alleles (P1 and P2). A significant difference in plasma triglyceride was detected among the different apobec-1 genotypes in the CAD patients (P<0.05). Our study could provide the basis for elucidating the interaction between genetic variation of the apobec-1 gene and disorders related to lipid metabolism.

• Journal of Animal Science and Technology
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• 제49권6호
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• pp.719-728
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• 2007

CSRP3, APOBEC2, CAV1, CAV2 및 CAV3 유전자들은 포유동물에서 도체와 육질 형질에 중요한 역할을 하는 것으로 보고되고 있다. 따라서, 이 유전자들의 단일염기다형(Single nucleotide poly- morphism; SNP)을 8개의 다른 소의 품종에서 확인한 결과 coding region에서 caveolin family 유전자에서 9개의 SNP, CSRP3유전자에서 1개의 SNP 및 APOBEC2 유전자에서 3개의 SNP가 존재함을 확인하였다. 이 coding region의 SNP들은 PCR-RFLP 방법에 의해 재확인하였으며 이들 유전자의 intronic region에서도 9개의 SNP가 존재함을 확인할 수 있었다. 8개의 다른 품종 소에 각 유전자들의 SNP들을 이용하여 유전자 빈도를 확인한 결과 CAV2, CAV3, CSRP3 및 APOBEC2 유전자의 SNP 중에서 5개가 품종간에서 유의적으로 차이가 있음을 확인할 수 있었다. 이 SNP들은 차후 검증작업을 통하여 육질관련 형질 마커로 이용될 수 있을 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제23권3호
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• pp.181-189
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• 2019

Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with $50{\mu}M$ curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%-8.05% to 27.63%-35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by $50{\mu}M$ curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the edito-some in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.

• Genomics & Informatics
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• 제19권4호
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• pp.40.1-40.11
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• 2021

Mutation signatures represent unique sequence footprints of somatic mutations resulting from specific DNA mutagenic and repair processes. However, their causal associations and the potential utility for genome research remain largely unknown. In this study, we performed PanCancer-scale correlative analyses to identify the genomic features associated with tumor mutation burdens (TMB) and individual mutation signatures. We observed that TMB was correlated with tumor purity, ploidy, and the level of aneuploidy, as well as with the expression of cell proliferation-related genes representing genomic covariates in evaluating TMB. Correlative analyses of mutation signature levels with genes belonging to specific DNA damage-repair processes revealed that deficiencies of NHEJ1 and ALKBH3 may contribute to mutations in the settings of APOBEC cytidine deaminase activation and DNA mismatch repair deficiency, respectively. We further employed a strategy to identify feature-driven, de novo mutation signatures and demonstrated that mutation signatures can be reconstructed using known causal features. Using the strategy, we further identified tumor hypoxia-related mutation signatures similar to the APOBEC-related mutation signatures, suggesting that APOBEC activity mediates hypoxia-related mutational consequences in cancer genomes. Our study advances the mechanistic insights into the TMB and signature-based DNA mutagenic and repair processes in cancer genomes. We also propose that feature-driven mutation signature analysis can further extend the categories of cancer-relevant mutation signatures and their causal relationships.