• Molecules and Cells
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• 제42권1호
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• pp.8-16
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• 2019

Mutations in the ${\beta}-catenin$ gene (CTNNB1) have been implicated in the pathogenesis of some cancers. The recent development of cancer genome databases has facilitated comprehensive and focused analyses on the mutation status of cancer-related genes. We have used these databases to analyze the CTNNB1 mutations assembled from different tumor types. High incidences of CTNNB1 mutations were detected in endometrial, liver, and colorectal cancers. This finding agrees with the oncogenic role of aberrantly activated ${\beta}-catenin$ in epithelial cells. Elevated frequencies of missense mutations were found in the exon 3 of CTNNB1, which is responsible for encoding the regulatory amino acids at the N-terminal region of the protein. In the case of metastatic colorectal cancers, in-frame deletions were revealed in the region spanning exon 3. Thus, exon 3 of CTNNB1 can be considered to be a mutation hotspot in these cancers. Since the N-terminal region of the ${\beta}-catenin$ protein forms a flexible structure, many questions arise regarding the structural and functional impacts of hotspot mutations. Clinical identification of hotspot mutations could provide the mechanistic basis for an oncogenic role of mutant ${\beta}-catenin$ proteins in cancer cells. Furthermore, a systematic understanding of tumor-driving hotspot mutations could open new avenues for precision oncology.

• BMB Reports
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• 제31권6호
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• pp.578-584
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• 1998

In a previous paper (Kim et al., 1996a), the immediate 5' -flanking region and coding region of the human UDP-N -acetylglucosamine:-D-mannoside-1,4-Nacetylglucosaminyltransferase III (N-acetylglucosaminyitransferase- III; GnT-III) gene was reported, isolated and analyzed. Herein, we report on amplification of a new 5' -noncoding region of the GnT-III mRNA by single-strand ligation to single-stranded cDNA-PCR (5' -RACE PCR) using poly(A)+ RNA isolated from human fetal liver cells. A cDNA clone was obtained with 5' sequences (96 bp) that diverged seven nucleotides upstream from the ATG (+1) start codon. A concensus splice junction sequence, TCTCCCGCAG, was found immediately 5' to the position where the sequences of the cDNA diverged. The result suggested the presence of an intron in the 5' -noncoding region and that the cDNA was an incompletely reversetranscribed cDNA product derived from an mRNA containing a new noncoding exon. When mRNA expression of GnT-III in various human tissues and cancer cell lines was examined, Northern blot analysis indicated high expression levels of GnT-III in human fetal kidney and brain tissues, as well as for a number of leukemia and lymphoma cancer cell lines. Promoter activities of the 5' -flanking regions of exon 1 and the new noncoding region were measured in a human hepatoma cell line, HepG2, by luciferase assays. The 5'-flanking region of exon 1 was the most active, whilst that of exon 2 was inactive.

• 한국가금학회지
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• 제32권4호
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• pp.239-244
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• 2005

Uncoupling protein(UCP)은 갈색 지방세포에서 특이적으로 발현하고 있으며 복잡한 세포의 열 생산 작용에 관여한다고 알려져 있다. 본 연구는 한국 재래 닭 집단의 UCP 유전자 내에 존재하는 SNP를 검출하였다. 한국 재래 닭 집단의 UCP유전자 exon 3지역의 염기서열 분석 결과 1316 bp에서 T염기가 C염기로 치환되어짐을 확인하였다. T+11316C 지역의 PCR-RFLP 분석을 위해 제한효소 Afl III를 사용하였다. 한국 재래닭 집단내 유전자형 빈도는 TT가 0.7875, TC가 0.1875 그리고 CC가 0.025로 검출되었으며 대립유전자의 빈도는 T가 0.881 그리고 C가 0.119로 나타났다. 또한 검출된 SNP가 경제형질에 미치는 영향을 분석한 결과 한국 재래 닭 집단의 T/T 유전자형과 C/C유전자형에서 일당 산란율에서 통계적으로 유의한 차이가 있음을 확인하였다. 본 연구의 결과는 향후 더 많은 UCP 유전자와 관련된 연구와 한국 재래 닭의 육종 전략에 도움이 될 것으로 사료된다.

• 생명과학회지
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• 제17권9호통권89호
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• pp.1303-1307
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• 2007

A tumor suppressor, merlin is a member of ERM family proteins. It consists of N-terminal FERM domain, ${\alpha}-helical$ region, and C-terminal domain. Alternative splicing of merlin's mRNA generates two isotypes of merlin. Isotype I, which has exon17 at the C-terminus instead of exon16 in isotype II, is known to have tumor suppressor activity. Like other ERM proteins, the C-terminal domain of merlin isotype I interacts to its FERM domain. That of isotype II, however, was reported not to bind FERM domain despite the large common part of C-terminal domain, which possibly binds FERM domain. Here, we show the binding of FERM domain to both C-terminal domains of merlin's two isotypes by isothermal titration calorimetry. These results support that merlin isotype II also can form a closed conformation or a multimer by intramolecular or intermolecular interactions using their FERM domain and C-terminal domain.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.134-134
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• 2002

In order to investigate whether genetic polymorphisms in the mEH exon3 (Tyr139His), exon4 (His113Arg) interact with the formation of MN in benzene exposed workers, the PCR-RFLP based genotyping of 76 exposed and 115 controls were performed and cytokinesis-block micronucleus (CBMN) analysis of 56 exposed and 53 controls was employed.(omitted)

• Archives of Pharmacal Research
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• 제21권1호
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• pp.35-40
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• 1998

Human cytochrome P450 4F2 shows high regioselectivity in hydroxylation of stearic acid and leukotriene $ B_4.$ As a first step of its regulation study, human cytochrome P450 4F2 genomic DNA was isolated from liver of a person who was administered clofibrate for 10 years. From Southern hybridization, restriction enzyme digestion and sequencing experiments, isolated genomic DNA fragment was found to contain around 32 Kb DNA and more than 20 Kb of $5^I$ end regulatory region. Sequences of the structural gene region revealed exon 1 and exon 2. Further regulation studies would elucidate the feedback mechanisms of the oxidative degradation of fatty acids, inflammatory response and the clearance of leukotriene B4 in the liver. Furthermore, regulation study of this gene could explain the species difference in responses to peroxisome proliferator and help in the safety evaluation of peroxisome proliferating chemicals to human being.

• 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 Interdisciplinary Genomics
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• 제1권1호
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• pp.1-5
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• 2019

Progressive weakness of skeletal muscle is the hallmark of muscular dystrophies. It is often accompanied by cardiomyopathy and respiratory insufficiency. It has generally been perceived as incurable diseases, while the advent of genetic therapy is changing the paradigm. Most research and achievements have been for the treatment of Duchenne muscular dystrophy, while it is promising to hope for therapies for other myopathies. Drugs for nonsense read-through and exon skipping are already approved for clinical use in Europe and the United States, respectively. Gene therapy using adeno-associated virus is in early phase of clinical trial. In this review, most promising genetic therapies will be briefly described.

• Journal of Genetic Medicine
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• 제20권2호
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• pp.46-51
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• 2023

Exonic copy number variation (CNV), involving deletions and duplications at the gene's exon level, presents challenges in detection due to their variable impact on gene function. The study delves into the complexities of identifying large CNVs and investigates less familiar but recurrent exonic CNVs, notably enriched in East Asian populations. Examining specific cases like DRC1, STX16, LAMA2, and CFTR highlights the clinical implications and prevalence of exonic CNVs in diverse populations. The review addresses diagnostic challenges, particularly for single exon alterations, advocating for a strategic, multi-method approach. Diagnostic methods, including multiplex ligation-dependent probe amplification, droplet digital PCR, and CNV screening using next-generation sequencing data, are discussed, with whole genome sequencing emerging as a powerful tool. The study underscores the crucial role of ethnic considerations in understanding specific CNV prevalence and ongoing efforts to unravel subtle variations. The ultimate goal is to advance rare disease diagnosis and treatment through ethnically-specific therapeutic interventions.

• BMB Reports
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• 제56권12호
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• pp.625-632
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• 2023

Nonsense-mediated mRNA decay (NMD) is both a quality control mechanism and a gene regulation pathway. It has been studied for more than 30 years, with an accumulation of many mechanistic details that have often led to debate and hence to different models of NMD activation, particularly in higher eukaryotes. Two models seem to be opposed, since the first requires intervention of the exon junction complex (EJC) to recruit NMD factors downstream of the premature termination codon (PTC), whereas the second involves an EJC-independent mechanism in which NMD factors concentrate in the 3'UTR to initiate NMD in the presence of a PTC. In this review we describe both models, giving recent molecular details and providing experimental arguments supporting one or the other model. In the end it is certainly possible to imagine that these two mechanisms co-exist, rather than viewing them as mutually exclusive.