• 산업기술연구
• /
• 제42권1호
• /
• pp.29-36
• /
• 2022

The CRISPR system has revolutionized gene editing field. Cas9-mediated gene editing such as Indel induction or HDR enable targeted gene disruption or precise correction of mutation. Moreover, CRISPR-based new editing tools have been developed such as base editors. In this review, we focus on gene editing in human pluripotent stem cells, which is principal technique for gene correction therapy and disease modeling. Pluripotent stem cell-specific drug YM155 enabled selection of target gene-edited pluripotent stem cells. Also, we discussed base editing for treatment of congenital retina disease. Adenine base editor delivery as RNP form provide an approach for genetic disease treatment with safe and precise in vivo gene correction.

• Industrial Engineering and Management Systems
• /
• 제16권1호
• /
• pp.64-79
• /
• 2017

Identifying disease genes from human genome is a critical task in biomedical research. Important biological features to distinguish the disease genes from the non-disease genes have been mainly selected based on traditional feature selection approaches. However, the traditional feature selection approaches unnecessarily consider many unimportant biological features. As a result, although some of the existing classification techniques have been applied to disease gene identification, the prediction performance was not satisfactory. A small set of the most important biological features can enhance the accuracy of disease gene identification, as well as provide potentially useful knowledge for biologists or clinicians, who can further investigate the selected biological features as well as the potential disease genes. In this paper, we propose a new stepwise random forests (SRF) approach for biological feature selection and disease gene identification. The SRF approach consists of two stages. In the first stage, only important biological features are iteratively selected in a forward selection manner based on one-dimensional random forest regression, where the updated residual vector is considered as the current response vector. We can then determine a small set of important biological features. In the second stage, random forests classification with regard to the selected biological features is applied to identify disease genes. Our extensive experiments show that the proposed SRF approach outperforms the existing feature selection and classification techniques in terms of biological feature selection and disease gene identification.

• The Plant Pathology Journal
• /
• 제17권2호
• /
• pp.83-87
• /
• 2001

Disease resistance in plants is often controlled by gene-for-gene mechanism in which avirulence (avr) gene products encoding by pathogens are specifically recognized, either directly or indirectly by plant disease resistance (R) gene products. Recent studies arising from molecular cloning of a number of R genes from various plant species that confer resistance to different pathogens and corresponding avr genes from various pathogens resulted in the accumulation of a wealth of knowledge on mode of action of gene-for-gene interaction. Specially, members of the NBS-LRR class of R genes encoding proteins containing a nucleotide binding site (NBS) and carboxyl-terminal leucine-rich repeats (LRRs) confer resistance to very different types of phytopathogens, such as bacteria, fungi, oomycetes, viruses, nematodes and aphids. This article reviewed the molecular events that occur up-stream of defense response pathway, specially, bacterial avr gene protein recognition mediated by NBS-LRR type R gene product in plant based on current research results of well studied model plants.

• 대한유전성대사질환학회지
• /
• 제5권1호
• /
• pp.9-17
• /
• 2005

Homocystinuria is a metabolic disorder caused by a deficiency of cystathionine ${\beta}$-synthase (CBS). Patients with homocystinuria show clinical symptoms such as mental retardation, lens dislocation, vascular disease with life-threatening thromboembolisms and skeletal deformities. Generally, the major treatments for CBS deficiency include pharmacologic doses of pyridoxine or dietary restriction of methionine. However, there is no effective treatment for this disease up till today and gene therapy can be an attractive novel approach to treatment of the disease. We investigated whether a recombinant adeno-associated virus could be used as a CBS gene transfer vector to reduce the excessive homocysteine level in the homocystinuria mouse model. Recombinant adeno-associated virus vector encoding the human CBS gene (rAAV-hCBS), driven by EF1-a promoter, was infused into CBS-deficient mice ($CBS^{-/-}$) via intramuscular (IM) and intraperitoneal (IP) injection. IP injection was more efficient than IM injection for prolongation of lives and reduction of plasma homocysteine levels. After 2 weeks of gene transfer by IP injection, serum homocysteine level was significantly decreased in treated mice compared with the age-matched controls and the life span was extended about 1.5 times. Also, increased expression of CBS gene was observed by immunohistochemical staining in livers of treated $CBS^{-/-}$ mice and microvesicular lipid droplets was decreased in cytoplasm of liver. These results demonstrate the possibility and efficacy of gene therapy by AAV gene transfer in homocystinuria mice.

• 한국작물학회:학술대회논문집
• /
• 한국작물학회 2022년도 추계학술대회
• /
• pp.201-201
• /
• 2022

Rice bakanae disease is a serious global threat in major rice-cultivating regions worldwide causing high yield loss. It is caused by the fungal pathogen Fusarium fujikuroi. Varying degree of resistance or susceptibility to bakanae disease had been reported among Korean japonica rice varieties. We developed a modified in vitro bakanae disease bioassay method and tested 31 Korean japonica rice varieties. Nampyeong and Samgwang varieties showed highest resistance while 14 varieties including Junam and Hopum were highly susceptible with 100% mortality rate. We carried out mapping QTLs for bakanae disease resistance with four F2:F3 populations derived from the crosses between Korean japonica rice varieties. The Kompetitive Allele-Specific PCR (KASP) markers developed in our laboratory based on the SNPs detected in Korean japonica rice varieties were used in genotyping F2 plants in the populations. We found four major QTLs on chromosome 1, 4, 6, and 9 with LOD scores of 21.4, 6.9, 6.0, and 60.3, respectively. In addition, we are doing map-based cloning of the QTLs on chromosome 1 and 9 which were found with Junam/Nampyeong F2:F3 population and Junam/Samgwang F2:F3 population, respectively. These QTLs will be very useful in developing bakanae disease resistant high quality rice varieties.

• 한국자원식물학회지
• /
• 제17권2호
• /
• pp.116-121
• /
• 2004

고려 인삼중 폐포와 4등급 이하를 유발시키는 90％이상이 적변삼이라고 불리는 인삼의 표피 색택이 붉은 삼이 그 원인이다. 이러한 적변삼은 미국삼보다는 고려 인삼에 서 다량 발견되는 바, 적변은 유전적 요인이 있다고 사료된다. 그러므로 이 연구의 목적은 RT-PCR을 이용하여 인삼적병에 내성을 가지는 유전자를 탐색하기 위하여 실시되었다. 고려인삼 3년근 1개체 중에서 적변이 발생된 부위와 건전 부위의 RNA를 추출하여 형성된 cDNA를 여러개의 random primer를 사용하여 PCR 증폭을 한 결과 정상 부위의 cDNA에서 발견되지 않는 band가 적변삼의 부위에서 발견되었다. 따라서 band가 형성된 부위의 유전자가 적변과 관련될 가능성이 있는 것으로 사료되고 이러한 유전자는 향후 염기서열을 분석하여 어떠한 유전자인지 판명을 하여야 하며 적변관련 유전자이면 선발마커로서 사용되고 또한 형질전환을 통한 적변내성 인삼계통을 육성할 수 있으며, 만약 적변과 관련이 없는 유전자로 판명된다면 더 많은 primer를 사용하여 적변관련 유전자를 탐색해야 할 것이다.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제2권2호
• /
• pp.164-168
• /
• 1999

Background: Wilson disease (WD) is an autosomal recessive disorder of copper transport and characterized by degenerative changes in the brain, liver dysfunction, and Kayser-Fleischer rings due to toxic accumulation of copper. Since the identification of Wilson disease gene (ATP7B), more than 80 mutations have been detected among the different ethnic groups. Methods: Twenty three children with Wilson disease were included in this study. They were all diagnosed by low serum ceruloplasmin and increased 24 hour urinary copper excretion with characteristic clinical findings. We analysed WD gene mutation by assessing the nucleotide sequence of exon 7, 8, 9 and 10 including intron-exon boundaries of ATP7B gene from genomic DNA. Results: Arg778Leu mutation was identified in 16 WD patients; three were homozygous and 13 were heterozygous for this mutation. Of the 46 alleles, 19 alleles had a Arg778Leu mutation (19/46=41%). Homozygote patients had neurologic forms of WD. Arg778Leu mutation was not found among 50 normal healthy persons. Conclusion: Arg778Leu mutation is a common mutation in Korean WD gene. Arg778Leu mutation screening might be used as a useful supplementary diagnostic test in some patients to confirm Wilson disease in Korea.

• Genomics & Informatics
• /
• 제6권3호
• /
• pp.153-156
• /
• 2008

Complex diseases such as stroke and cancer have two or more genetic loci and are affected by environmental factors that contribute to the diseases. Due to the complex characteristics of these diseases, identifying candidate genes requires a system-level analysis of the following: gene ontology, pathway, and interactions. A database and user interface, termed StrokeBase, was developed; StrokeBase provides queries that search for pathways, candidate genes, candidate SNPs, and gene networks. The database was developed by using in silico data mining of HGNC, ENSEMBL, STRING, RefSeq, UCSC, GO, HPRD, KEGG, GAD, and OMIM. Forty candidate genes that are associated with cerebrovascular disease were selected by human experts and public databases. The networked cerebrovascular disease gene maps also were developed; these maps describe genegene interactions and biological pathways. We identified 1127 genes, related indirectly to cerebrovascular disease but directly to the etiology of cerebrovascular disease. We found that a protein-protein interaction (PPI) network that was associated with cerebrovascular disease follows the power-law degree distribution that is evident in other biological networks. Not only was in silico data mining utilized, but also 250K Affymetrix SNP chips were utilized in the 320 control/disease association study to generate associated markers that were pertinent to the cerebrovascular disease as a genome-wide search. The associated genes and the genes that were retrieved from the in silico data mining system were compared and analyzed. We developed a well-curated cerebrovascular disease-associated gene network and provided bioinformatic resources to cerebrovascular disease researchers. This cerebrovascular disease network can be used as a frame of systematic genomic research, applicable to other complex diseases. Therefore, the ongoing database efficiently supports medical and genetic research in order to overcome cerebrovascular disease.

• 정보과학회 컴퓨팅의 실제 논문지
• /
• 제23권1호
• /
• pp.28-36
• /
• 2017

1990년대 게놈프로젝트 이후 유전자와 관련된 많은 연구가 진행되고 있다. 데이터 저장 기술의 발달로 연구의 결과물들은 다량의 문헌들로 기록되고 있으며, 이러한 문헌들은 새로운 생물학적 관계들을 추론하는 데이터로 유용하게 사용되고 있다. 이러한 이유로 본 연구에서는 생물학 문헌들을 활용하여 질병과 관련한 유전자를 추론하는 방법론에 대해서 제안한다. 문헌들을 제목과 본문으로 구분하고, 각 영역에서 등장한 유전자들을 추출한다. 제목 영역에서 추출된 유전자는 중심 유전자로 구분하고, 본문 영역에서 추출된 유전자는 제목에서 추출된 유전자와 관계를 갖는 주변 유전자로 구분한다. 이러한 과정을 각 문헌에 적용하여, 지역 유전자 네트워크를 구축한다. 구축된 지역 유전자 네트워크는 모두 연결하여 전역유전자 네트워크를 구축한다. 구축한 네트워크를 분석하여 질병 관련 유전자를 추론하였으며, 비교 실험을 통해 제안하는 방법론이 질병 관련 유전자를 추론하는 유용한 방법론임을 입증하였다.

• Animal cells and systems
• /
• 제7권3호
• /
• pp.255-259
• /
• 2003

Mutations in the factor Ⅴ gene are major risk markers for venous thrombosis. Several factors for blood coagulation have been related with cardiovascular disease. Ⅰ investigated genotype distribution for three mutations (G1691 A, A2379G and G2391 A) of the factor Ⅴ gene in the Korean population. Genotype frequencies were examined by polymerase chain reaction in 135 patients with coronary artery disease (CAD) and 116 healthy subjects. For the G1691A mutation (factor Ⅴ