• Title, Summary, Keyword: mutation

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Clonal plant as experimental organisms - DNA mutation rate evaluation in the radiation contaminated area of Fukushima Daiichi NPP accident

  • KANEKO, Shingo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • pp.25-25
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    • 2018
  • The Fukushima Daiichi Nuclear Power Plant accident in March 2011 caused severe radioactive contamination in the surrounding environment. Since the accident, much attention has been paid to the biological and genetic consequences of organism inhabiting the contaminated area. The effect of radiation exposure on genetic mutation rates is little known, especially for low doses and in situ conditions. Evaluating DNA mutation by low levels of radiation dose is difficult due to the rare mutation event and lack of sequence information before the accident. In this study, correlations with air dose levels and somatic DNA mutation rates were evaluated using Next Generation Sequencer for the clonal plant, Phyllostachys edulis. This bamboo is known to spread an identical clone throughout Japan, and it has the advantage that we can compare genetic mutation rate among identical clone growing different air dose levels. We collected 94 samples of P. edulis from 14 sites with air dose rates from $0.04{\sim}7.80{\mu}Gy/h$. Their clonal identity was confirmed by analysis using 24 microsatellite markers, and then, sequences among samples were compared by MIG sequence. The sequence data were obtained from 2,718 loci. About ~200,000 bp sequence (80 bp X 2,718 loci) were obtained for each sample, and this corresponds to about 0.01% of the genome sequence of P. edulis. In these sequences, 442 loci showed polymorphism patterns including recent origin mutation, old mutation, and sequence errors. The number of mutations per sample ranged from 0 to 13, and did not correlate with air dose levels. This result indicated that DNA mutations have not accumulated in P. edulis living in the air doses levels less than $10{\mu}Gy/h$. Our study also suggests that mutation rates can be assessed by selecting an appropriate experimental approach and analyzing with next generation sequencer.

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Evolutionary Programming of Applying Estimated Scale Parameters of the Cauchy Distribution to the Mutation Operation (코시 분포의 축척 매개변수를 추정하여 돌연변이 연산에 적용한 진화 프로그래밍)

  • Lee, Chang-Yong
    • Journal of KIISE:Software and Applications
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    • v.37 no.9
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    • pp.694-705
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    • 2010
  • The mutation operation is the main operation in the evolutionary programming which has been widely used for the optimization of real valued function. In general, the mutation operation utilizes both a probability distribution and its parameter to change values of variables, and the parameter itself is subject to its own mutation operation which requires other parameters. However, since the optimal values of the parameters entirely depend on a given problem, it is rather hard to find an optimal combination of values of parameters when there are many parameters in a problem. To solve this shortcoming at least partly, if not entirely, in this paper, we propose a new mutation operation in which the parameter for the variable mutation is theoretically estimated from the self-adaptive perspective. Since the proposed algorithm estimates the scale parameter of the Cauchy probability distribution for the mutation operation, it has an advantage in that it does not require another mutation operation for the scale parameter. The proposed algorithm was tested against the benchmarking problems. It turned out that, although the relative superiority of the proposed algorithm from the optimal value perspective depended on benchmarking problems, the proposed algorithm outperformed for all benchmarking problems from the perspective of the computational time.

Detection of Human Cytomegalovirus UL97 D605E Mutation in Korean Stem Cell Transplantation Recipients and Donors

  • Lee, Gyu-Cheol;Choi, Su-Mi;Lee, Chan Hee;Lee, Dong-Gun;Choi, Jung-Hyun;Yoo, Jin-Hong
    • Journal of Microbiology and Biotechnology
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    • v.23 no.8
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    • pp.1154-1158
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    • 2013
  • Ganciclovir resistance of human cytomegalovirus is associated with mutations in the viral UL97 gene and poses severe problems for immunocompromised patients. In this study, PCR-based restriction fragment length polymorphism and sequencing analyses detected the UL97 D605E mutation in all five clinical isolates from patients with ganciclovir-resistant human cytomegalovirus infection during prolonged ganciclovir therapy, whereas the M460V mutation was only present in 1 of 5 isolates. On the other hand, the detection rates of the D605E mutation in the stored available DNA samples from the donor and allogeneic stem cell transplantation recipients were 66.7% and 93.7%, respectively, suggesting that the presence of D605E mutation was not associated with the ganciclovir exposure. Although the D605E mutation may not be related to ganciclovir resistance, we suggest that this mutation could be an important molecular marker of human cytomegalovirus evolution in East Asian countries. Moreover, the restriction fragment length polymorphism method using the restriction enzyme HaeIII, which is generally used to detect the UL97 A591V mutation, could also detect the D605E mutation and may therefore be a useful tool for future research on the investigation of UL97 gene mutations.

BRAFV600E Mutation Analysis in Fine Needle Aspiration Biopsy Cytology and Formalin Fixed Paraffin Embedding Block of the Thyroid

  • Han, Kyung Hee;Park, Won Young;Lee, Young Nam
    • Korean Journal of Clinical Laboratory Science
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    • v.45 no.2
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    • pp.66-72
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    • 2013
  • Fine Needle Aspiration Biopsy Cytology (FNABC), which is known as the most accurate and cost-effective method for diagnosis of the thyroid nodule, may still result in indeterminate cases that are cellular paucity and show minor nuclear atypia. However, most cases are associated with suspicion of papillary thyroid carcinoma (PTC). A B-type Raf kinase (BRAF) mutation was found in about half of PTCs which is currently helping us to differentiate malignancies from benign lesions. Cases studied included 46 histological, confirmed PTC cases. FNABC 102 cell paucity and 74 atypia benign cases were previously diagnosed as suspicious of PTC using cytologic examination. These cases were analyzed for BRAF mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with a new restriction enzyme. In this study, the sensitivity and specificity were calculated and, BRAF mutation was detected by means of a histological method in 23 of 46 cases of PTC and no mutation was found in 22 cases. However, one case was not detected. In using FNABC, BRAF mutation was detected in 6 of 102 cases in cell paucity and in 11 of 74 cases in the atypia. Two cases were not detected in the atypia. The sensitivity and specificity of PCR-RFLP in FNABC were 60% and 97.4% respectively. Assessment of Formalin Fixed Paraffin Embedding (FFPE) block demonstrated similarly a 51.1% positive and 48.9% negative in PTC. Evaluation of BRAF mutation revealed high specificity and low sensitivity in using FNABC method. This study suggests that BRAF mutation analysis should be useful for the clinical diagnosis of PTC in FNABC with cytological findings suspicious for PTC.

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Prevalence and Clinical Profile of EGFR Mutation In Non-Small-Cell Lung Carcinoma Patients in Southwest China

  • Zhou, Juan;Song, Xing-Bo;He, He;Zhou, Yi;Lu, Xiao-Jun;Ying, Bin-Wu
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.965-971
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    • 2016
  • Aims: To investigate the distribution of epidermal growth factor receptor (EGFR) mutations, and explore any relationships with clinical characteristics in non-small-cell lung carcinoma (NSCLC) patients. Materials and Methods: EGFR mutations were assessed by ADx-ARMS in 261 NSCLC patients from West China Hospital of Sichuan University. Relationships between EGFR mutation and clinical characteristics were analyzed by SPSS. Results: The EGFR mutation rate was 48.7% (127/261), 19-del and L858R mutations occurred predominantly, accounting for 33.1% and 40.9%, respectively, in mutated cases. Moreover, 10.2% patients were found to carry double mutations. EGFR mutations occurred more frequently in women (57.5%) than in men (41.8%) (P=0.01), and were more frequent in non-smokers (61.2%) than in former or current smokers (31.2%) (P<0.00). In addition, they were more common in adenocarcinomas (52.8%) and adenosquamous carcinomas (42.8%) than in squamous cell carcinomas (14.8%) (p<0.00). However, only smoking history and pathological types, rather than gender, proved to be associated with EGFR mutations on multivariate logistic regression analysis. No significant differences in pathological stage and metastasis status were found between EGFR wild-type and mutated cases, although EGFR mutation type was related to pathological type (p=0.00) - 19-del, L858R and other mutation types respectively occurred in 34.2%, 42.5% and 23.3% of adenocarcinomas, but in 14.3%, 0% and 85.7% of non-adenocarcinomas. Conclusions: The EGFR mutation rate was 48.7% in NSCLCs in Southwest China, so that nearly 40% patients might benefit from targeted therapies. Smoking status and pathological types were independent predictors of EGFR mutation, while EGFR mutation type was related to only pathological type, rather than smoking status.

A Novel Frameshift Mutation of SLC26A4 in a Korean Family With Nonsyndromic Hearing Loss and Enlarged Vestibular Aqueduct

  • Sagong, Borum;Baek, Jeong-In;Lee, Kyu-Yup;Kim, Un-Kyung
    • Clinical and Experimental Otorhinolaryngology
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    • v.10 no.1
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    • pp.50-55
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    • 2017
  • Objectives. We aimed to identify the causative mutation for siblings in a Korean family with nonsyndromic hearing loss (HL) and enlarged vestibular aqueduct (EVA). The siblings were a 19-year-old female with bilateral profound HL and an 11-year-old male with bilateral moderately severe HL. Methods. We extracted genomic DNA from blood samples of the siblings with HL, their parents, and 100 controls. We performed mutation analysis for SLC26A4 using direct sequencing. Results. The two siblings were compound heterozygotes with the novel mutation p.I713LfsX8 and the previously described mutation p.H723R. Their parents had heterozygous mono-allelic mutations. Father had p.I713LfsX8 mutation as heterozygous, and mother had p.H723R mutation as heterozygous. However, novel mutation p.I713LfsX8 was not detected in 100 unrelated controls. Conclusion. Both mutations identified in this study were located in the sulfate transporter and anti-sigma factor antagonist domain, the core region for membrane targeting of SulP/SLC26 anion transporters, which strongly suggests that failure in membrane trafficking by SLC26A4 is a direct cause of HL in this family. Our study could therefore provide a foundation for further investigations elucidating the SLC26A4-related mechanisms of HL.

Relation between RASSF1A Methylation and BRAF Mutation in Thyroid Tumor (갑상선 종양에서 RASSF1A 메틸화와 BRAF 유전자 변이에 관한 연구)

  • Oh, Kyoung Ho;Jung, Kwang Yoon;Baek, Seung Kuk;Woo, Jeong Soo;Cho, Jae Gu;Kwon, Soon Young
    • International journal of thyroidology
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    • v.11 no.2
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    • pp.123-129
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    • 2018
  • Background and Objectives: Hypermethylation of the tumor suppressor gene RASSF1A and activating mutation of BRAF gene have been recently reported in thyroid cancers. To investigate the role of these two epigenetic and genetic alterations in thyroid tumor progression, methylation of RASSF1A and BRAF mutation were examined in thyroid tumors. Materials and Methods: During 2007 to 2017, 69 papillary carcinomas, 18 nodular hyperplasia, 3 follicular carcinomas, and 13 follicular adenomas were selected. The methylation-specific polymerase chain reaction (MSP) technique was used in detecting RASSF1A methylation and polymerase chain reaction (PCR)-single-stranded conformation polymorphism and sequencing were used for BRAF gene mutation study. Results: The hypermethylation of the RASSF1A gene was found in 84.6%, 100% and 57.9% of follicular adenomas, follicular carcinomas, and papillary carcinomas, respectively. Nodular hyperplasia showed a hypermethylation in 33.3%. The BRAF mutation at V600E was found in 60.7% of papillary carcinoma and 27.0% of nodular hyperplasia, but none of follicular neoplasms. The BRAF mutation was correlated with the lymph node metastasis and MACIS clinical stage. There is an inverse correlation between RASSF1A methylation and BRAF mutation in thyroid lesions. Conclusion: Epigenetic inactivation of RASSF1A through aberrant methylation is considered to be an early step in thyroid tumorigenesis, and the BRAF mutation plays an important role in the carcinogenesis of papillary carcinoma, providing a genetic marker.

The Effect of Heat Treatment on Biological Response and Mutation Frequency of Gamma Irradiated Rice Seeds (수도종자의 방사선조사에 있어서 열처리의 효과)

  • Chang-Yawl Harn;J. L.Won;Kwang-Tae Choi
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.10
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    • pp.45-50
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    • 1971
  • For the purpose of finding out the effect of heat treatment on biological response and mutation rate, rice seeds were heat treated before and after gamma irradiation. 1. At a dose of 20 KR, pre-irradiation heat treatment showed reduced biological damage and increased mutation rate as compared with non-heat treatment. 2. Mutation frequency was increased in post-treatment of heat shock than in pre-irradiation heat treatment and non-heat treatment. 3. Pre-irradiation heat treatment at 6$0^{\circ}C$ for 30 minutes markedly reduced the biological damage and increased the mutation rate. 4. Mutation spectrum in heat treatment was different from non-treatment.

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Thr-6Pro missense mutation in human lysosomal acid lipase (LAL) gene in patients with familial hypercholesterolemia in Korea

  • Hwang, Hye-Suk;Hwang, Jung-Hee;Kim, Hyun-Sup;Kim, Nam-Keun;Kim, Se-Jae;Lee, Chung-Choo;Chung, Ki-Wha
    • Journal of Genetic Medicine
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    • v.2 no.2
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    • pp.65-70
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    • 1998
  • Lysosomal acid lipase (LAL) plays a central role in the intracellular degradation of neutral lipids derived from plasma lipoproteins. In this study, we investigated the missense mutation within exon 2 of human LAL gene changing of codon -6 of prepeptide from threonine to proline. The Thr-6Pro mutation was detected by the HaeIII restriction fragment length polymorphism (RFLP) and single-strand conformation polymorphism (SSCP). We analyzed the mutation in subjects with 221 unrelated randomly selected control samples and 86 patients with familial hypercholesterolemia (FH) in Korea. We observed that mutation is present with high frequency in Korea compared to other populations studied previously. The frequency of PP homozygote in the FH group was observed considerably higher than that of control. However, there was no significant difference of genotype frequency between two groups. These results, together with the fact that plasma lipids and lipoproteins levels between genotypes showed no statistical difference, suggest that the Thr-6Pro mutation in the LAL gene may have no association with the increased risk of FH development.

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A novel de novo mosaic mutation in PHEX in a Korean patient with hypophosphatemic rickets

  • Yang, Misun;Kim, Jinsup;Yang, Aram;Jang, Jahyun;Jeon, Tae Yeon;Cho, Sung Yoon;Jin, Dong-Kyu
    • Annals of Pediatric Endocrinology and Metabolism
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    • v.23 no.4
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    • pp.229-234
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    • 2018
  • X-linked hypophosphatemic rickets is caused by loss-of-function mutations in PHEX, which encodes a phosphate-regulating endopeptidase homolog. We report a 26-year-old man with X-linked hypophosphatemic rickets who showed decreased serum phosphate accompanied by bilateral genu valgum and short stature. He had received medical treatment with vitamin D (alfacalcidol) and phosphate from the age of 3 to 20 years. He underwent surgery due to valgus deformity at the age of 14 and 15. Targeted gene panel sequencing for Mendelian genes identified a nonsense mutation in PHEX (c.589C>T; p.Gln197Ter) and a mosaic pattern where only 38% of sequence reads showed the variant allele. This mutation was not found in his mother, who had a normal phenotype. This is a case of a sporadic nonsense mutation in PHEX and up to date, this is the first case of a mosaic mutation in PHEX in Korea.