• Journal of Korean Neurosurgical Society
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• 제63권5호
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• pp.559-565
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• 2020

Objective : Conflicting results regarding SOX17 genes and the risk of intracranial aneurysms (IA) exist in the Korean population, although significant positive correlations were noted in genome-wide association studies in European and Japanese populations. Therefore, we aimed to investigate an association between SOX17 gene variants and IA using exome sequencing data. Methods : This study included 26 age-gender matched IA patients and 26 control subjects. The SOX17 gene variants identified from whole-exome sequencing data were examined. Genetic associations to estimate odds ratio (OR) and 95% confidence interval (CI) were performed using the software EPACTS. Results : The mean age of the IA and control groups were 51.0±9.3 years and 49.4±14.3 years, respectively (p=0.623). Seven variants of SOX17, including six single nucleotide polymorphisms and one insertion and deletion, were observed. Among these variants, rs12544958 (A>G) showed the most association with IA, but the association was not statistically significant (OR, 1.97; 95% CI, 0.81-4.74; p=0.125). Minor allele frequencies of the IA patients and controls were 0.788 and 0.653, respectively. None of the remaining variants were significantly associated with IA formation. Conclusion : No significant association between SOX17 gene variants and IA were noted in the Korean population. A large-scale exome sequencing study is necessary to investigate any Korean-specific genetic susceptibility to IA.

• Animal cells and systems
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• 제12권3호
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• pp.137-141
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• 2008

Molecular cloning revealed the three isoforms($Ca_v3.1,\;Ca_v3.2,\;and\;Ca_v3.3$) of the T-type calcium channel subfamily. Expression studies exhibited their distinctive electrophysiological and pharmacological properties, accounting for diverse properties of T-type calcium channel currents previously characterized from isolated cells. However, electrophysiological properties of ion channels have shown to be more diversified by their splice variants. We here searched splice variants of rat $Ca_v3.1$ T-type channel by reverse-transcription-polymerase chain reaction(RT-PCR) to further explore diversity of $Ca_v3.1$. Interestingly, analyses of cloned RT-PCR products displayed that there were at least four splicing variants of rat $Ca_v3.1$ in the loop connecting repeats III and IV. Southern blot analyses indicated that the predominantly detected variant in brain was $Ca_v3.1a$(492 bp), which were rarely detected in most of peripheral tissues. Other two variants($Ca_v3.1c$, 546 bp; $Ca_v3.1d$, 525 bp) were detected in most of the tissues examined. The smallest isoform($Ca_v3.1b$, 471 bp) was rarely detected all the tissues. Electrophysiological characterization of the splicing variants indicated that the splice variants differ in inactivation kinetics and the voltage dependence of activation and inactivation as well.

• Molecules and Cells
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• 제41권5호
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• pp.465-475
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• 2018

The advent of massively parallel sequencing, also called next-generation sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AML-related genes. Notably, SIN3A expression shows prognostic value in AML. A newly designed method, referred to as "hot-zone" analysis, detected two putative functional noncoding variants that can alter transcription factor binding affinity near PPP1R10 and SRSF1. Moreover, the functional importance of the SRSF1 noncoding variant was further investigated by luciferase assays, which showed that the variant is critical for the regulation of gene expression leading to leukemogenesis. We expect that further functional investigation of these coding and noncoding variants will contribute to a more in-depth understanding of the underlying molecular mechanisms of AML and the development of targeted anti-cancer drugs.

• Genomics & Informatics
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• 제21권4호
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• pp.48.1-48.8
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• 2023

Liver cancer is the fourth leading cause of death worldwide. Well-known risk factors include hepatitis B virus and hepatitis C virus, along with exposure to aflatoxins, excessive alcohol consumption, obesity, and type 2 diabetes. Genomic variants play a crucial role in mediating the associations between these risk factors and liver cancer. However, the specific variants involved in this process remain under-explored. This study utilized a bioinformatics approach to identify genetic variants associated with liver cancer from various continents. Single-nucleotide polymorphisms associated with liver cancer were retrieved from the genome-wide association studies catalog. Prioritization was then performed using functional annotation with HaploReg v4.1 and the Ensembl database. The prevalence and allele frequencies of each variant were evaluated using Pearson correlation coefficients. Two variants, rs2294915 and rs2896019, encoded by the PNPLA3 gene, were found to be highly expressed in the liver tissue, as well as in the skin, cell-cultured fibroblasts, and adipose-subcutaneous tissue, all of which contribute to the risk of liver cancer. We further found that these two SNPs (rs2294915 and rs2896019) were positively correlated with the prevalence rate. Positive associations with the prevalence rate were more frequent in East Asian and African populations. We highlight the utility of this population-specific PNPLA3 genetic variant for genetic association studies and for the early prognosis and treatment of liver cancer. This study highlights the potential of integrating genomic databases with bioinformatic analysis to identify genetic variations involved in the pathogenesis of liver cancer. The genetic variants investigated in this study are likely to predispose to liver cancer and could affect its progression and aggressiveness. We recommend future research prioritizing the validation of these variations in clinical settings.

• 한국산림과학회지
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• 제95권4호
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• pp.435-442
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• 2006

국내 소나무 19개 집단을 대상으로 cpSSR 표지자 분석을 통해서 관찰된 28개 변이체로부터 총 167개의 독특한 haplotype이 확인되었고, 동일한 haplotype을 보인 13개체가 10집단에 고르게 분포하였으며, 각 집단에서 관찰된 유효 haplotype의 수는 평균 13.37개로 나타났다. cpSSR haplotype의 집단내 다양도(He)는 0.987로 계산되어 기존의 임목을 대상으로 한 연구에서 보고된 수치와 유사하거나 약간 높은 수치를 보였다. 각 haplotype을 구성하고 있는 cpSSR 변이체를 대상으로 각 집단에서의 다양성(S.I.)을 계산한 결과 강원도 영월집단이 1.109로 계산되어 가장 높은 수치를 보였으며, 경북 문경집단이 0.411로 가장 낮은 수치를 보였다(평균 0.887), 관찰된 cpSSR 변이체들의 대부분이 19개 집단에 공통적으로 존재하는 것으로 나타났으며(97.62%), 집단간에 cpSSR 변이체 분화는 미약한 것으로 나타났는데(${\Phi}_{ST}=0.024$) cpSSR 표지자의 높은 돌연변이 발생빈도가 주요 원인인 것으로 추정된다. 반면에 비교 가능한 173개 집단 쌍 간에 동일한 haplotype이 전혀 존재하지 않는 집단 쌍이 39쌍으로 나타나 집단간의 유전적 유연관계에 대한 직접적인 비교가 불가능했으며, 따라서 분석된 19개 집단간에 유전적 교류가 자유롭게 일어나지 않는 것으로 나타났다. cpSSR 표지자 변이체의 분포양상과 기존의 I-SSR 표지자 변이체의 분포양상을 비교 고찰해 볼 때 국내 소나무 유전자원의 효율적인 관리를 위해서는 분석된 소나무 집단의 현재 위치 정보와 유전정보가 함께 고려되어야할 것으로 생각된다.

• Genomics & Informatics
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• 제18권1호
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• pp.6.1-6.9
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• 2020

Acute leukemia represents the most common pediatric malignancy comprising diverse subtypes with varying prognosis and treatment outcomes. New and targeted treatment options are warranted for this disease. Patient-derived xenograft (PDX) models are increasingly being used for preclinical testing of novel treatment modalities. A novel approach involving targeted error-corrected RNA sequencing using ArcherDX HemeV2 kit was employed to compare 25 primary pediatric acute leukemia samples and their corresponding PDX samples. A comparison of the primary samples and PDX samples revealed a high concordance between single nucleotide variants and gene fusions whereas other complex structural variants were not as consistent. The presence of gene fusions representing the major driver mutations at similar allelic frequencies in PDX samples compared to primary samples and over multiple passages confirms the utility of PDX models for preclinical drug testing. Characterization and tracking of these novel cryptic fusions and exonal variants in PDX models is critical in assessing response to potential new therapies.

• 정보관리학회지
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• 제27권1호
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• pp.249-267
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• 2010

h-지수는 개인의 연구성과를 측정하는 지표로 지수의 강건성과 계산의 용이성 등이 인정되면서 이를 보완하는 다양한 변형지수들이 연구되었으며, 이 지수들을 이용하여 연구자 개인의 영향력 평가는 물론, 저널, 학과, 대학, 연구소 등 기관단위 평가를 하려는 시도가 이루어지고 있다. h-지수를 이용한 기관단위의 평가 방법으로는 기관 h-지수, 평균 h-지수, 메타 h-지수 등 세 가지가 있으며, 본 연구에서는 국내 10개 경영대학을 대상으로 h-지수 및 변형지수들의 특징 및 상관관계를 살펴 본 후, 위의 세 가지 방법을 모두 적용하여 각 방법론을 비교 분석하였다.

• 대한수의학회지
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• 제23권2호
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• pp.173-178
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• 1983

This paper deals with the isolation of citrate-utilizing variants of Escherichia coli ($Cit^+$ E. coli) from the animals, their biochemical reactivity and antibiotic susceptibility, and whether the citrate utilizing ability is transmissible. One hundred arid twenty-three isolates of $Cit^+$ E. coli were obtained from cattle and pigs. but from other animals, no isolates were obtaied. Antibiotic susceptibility testing of $Cit^+$ E. coli was performed by the agar dilution method, using the following 9 antibiotics, chloramphenicol(CP), tetracycline(TC), streptomycine(SM), kanamycin(KM), colistin(CL), gentamicin(GM), cephaloridine(CR), aminobenzycillin and nalidixic acid(NA). All the variants tested were susceptible to KM, CL, GM, CR and NA. Of all the variants, 80(65%) were resistant to the drugs tested and resistance to TC and SM was most frequent. The transmission of the ability to utilize citrate on Simmons citrate agar at $37^{\circ}C$ was demonstrated in 78(67.8%) out of the 115 $Cit^+$ E. coli. There were no significant difference in the transfer rates of citrate utilizing ability between resistant and susceptible variants to above 9 drugs. Of 123 isolates, 8 were lost their citrate utilizing ability, spontaneously.

• BMB Reports
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• 제37권2호
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• pp.167-176
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• 2004

Although efficient antiviral lamivudine is used for HBV-infected patients, a prolonged treatment with nucleoside analogs often results in lamivudine-resistant variants. In this study, we evaluated the fidelity of the lamivudine-resistant variants. The FLAG-tagged wild-type (FPolE) and Met550 variants (FPolE/M550A, M550V, and M550I) of HBV DNA polymerases were expressed in insect cells then purified. Like many other reverse transcriptases, no $3'{\rightarrow}5'$ exonuclease activity was detected in the HBV DNA polymerase. Since there is no proofreading activity, then the use of the site-specific nucleotide misincorporation method is beneficial. From the $f_{ins}$ value analysis, it is evident that M550I and M550V exhibit higher fidelity values than the wild-type HBV DNA polymerase, while M550A exhibits similar fidelity values. It is therefore suggested that lamivudine resistance comes from the stringency to dNTP binding and the discrimination of dCTP and lamivudine in M550V and M550I.

• Genomics & Informatics
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• 제8권3호
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• pp.142-149
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• 2010

In recent years, genome-wide association (GWA) studies have successfully led to many discoveries of genetic variants affecting common complex traits, including height, blood pressure, and diabetes. Although GWA studies have made much progress in finding single nucleotide polymorphisms (SNPs) associated with many complex traits, such SNPs have been shown to explain only a very small proportion of the underlying genetic variance of complex traits. This is partly due to that fact that most current GWA studies have relied on single-marker approaches that identify single genetic factors individually and have limitations in considering the joint effects of multiple genetic factors on complex traits. Joint identification of multiple genetic factors would be more powerful and provide a better prediction of complex traits, since it utilizes combined information across variants. Recently, a new statistical method for joint identification of genetic variants for common complex traits via the elastic-net regularization method was proposed. In this study, we applied this joint identification approach to a large-scale GWA dataset (i.e., 8842 samples and 327,872 SNPs) in order to identify genetic variants of obesity for the Korean population. In addition, in order to test for the biological significance of the jointly identified SNPs, gene ontology and pathway enrichment analyses were further conducted.