• BMB Reports
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• 제51권1호
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• pp.1-2
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• 2018

Positive selection on a new beneficial mutation generates a characteristic pattern of DNA sequence polymorphism when it reaches an intermediate allele frequency. On genome sequences of African Drosophila melanogaster, we detected such signatures of selection at 37 candidate loci and identified "sweeping haplotypes (SHs)" that are increasing or have increased rapidly in frequency due to hitchhiking. Based on geographic distribution of SH frequencies, we could infer whether selective sweeps occurred starting from de novo beneficial mutants under simple constant selective pressure. Single SHs were identified at more than half of loci. However, at many other loci, we observed multiple independent SHs, implying soft selective sweeps due to a high beneficial mutation rate or parallel evolution across space. Interestingly, SH frequencies were intermediate across multiple populations at about a quarter of the loci despite relatively low migration rates inferred between African populations. This invokes a certain form of frequency-dependent selection such as heterozygote advantage. At one locus, we observed a complex pattern of multiple independent that was compatible with recurrent frequency-dependent positive selection on new variants. In conclusion, genomic patterns of positive selection are very diverse, with equal contributions of hard and soft sweeps and a surprisingly large proportion of frequency-dependent selection in D. melanogaster populations.

• 한국환경성돌연변이발암원학회지
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• 제23권1호
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• pp.16-22
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• 2003

Single nucleotide polymorphisms (SNPs) are alterations in DNA base that occur most frequently throughout the human genome. The SNPs of DNA repair genes, hMLH1, hMSH2 and ATM, among 100 Korean people were analyzed using Dynamic Allele specific Hybridization (DASH) techniques. Mutation at the position of exon 38 (GA) and exon 10 (CG) of ATM gene, mutation at the position of exon 8 (AG), and exon 1 (AG) of hMLH1 gene and exon 14 (AG) of hMSH2 gene were investigated. No mutation at the selected position of ATM gene and hMSH1 gene was found. However, while there was no mutation at the position of exon of hMSH2 gene, mutation was found at the promotion region (CT) with the frequency of 24% CC, 36% CT and 62% TT genotyes. This results might be used as baseline data for research on SNP of Korean population.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 1996년도 제19회정기학술대회(The 19th Symposium of the Korean Society of Environmental Toxicology)
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• pp.64-64
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• 1996

Transgenic animal and cell line models which are recently developed in toxicology field combined with molecular biological technique, are powerful tools for studying of mutation in vivo and in vitro, respectively. The Big Blue mutagenesis assay system is one of the most widely used transgenic systems. Especially, for the study of direct acting mutagens, Big Blue cell line is very useful and powerful to evaluate mutagenicity because the mutation frequency and mutationspectrlun showed no distinct differences between cell line and animal. The Big Blue cell lines carry stably integrated copies of lambda shuttle vector containing lac I gene as a mutational target. These lambda shuttle vectors are useful for various mutagenesis related studies in eukaryotic system due to their ability to be exposed mutagen and then transfer a suitable target DNA sequence to it convenient organism for analysis. We tried to assess the mutagenic effect of 4-NQO with Big Blue cell line. After the treatment of 4-NQO, genomic DNA was isolated and lambda shuttle vector was packaged by in Vitro packaging and then these were plated on bacterial host in the presence of X-gal to screen mutation in the lac I. We determined MF as a ratio of blue plaques versus colorless plaques and now undergoing the mutation spectrum of 4-NQO in lac J gene sequence.

• 분석과학
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• 제15권3호
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• pp.190-195
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• 2002

본 연구에서는 ion-pair reversed-phase high performance liquid chromatography (IP-RP-HPLC)방식을 이용한 denaturing high performance liquid chromatography (DHPLC)방법을 사용하여 기관지 천식을 조절하는 ${\beta}_2$-교감신경수용체 유전자의 돌연변이를 검출하였다. 50명의 천식 환자의 혈액에서 genomic DNA를 추출하여 중합효소연쇄반응 (polymerase chain reaction, PCR)을 이용해 증폭하고, 그 산물을 DHPLC로 분석한 결과, 50개의 시료 가운데 15개 (30%)의 돌연변이를 검출하였다. 최종적으로 유전자 염기서열결정법을 통해 DHPLC의 돌연변이 검출률이 정확함을 확인하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2521-2523
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• 2013

Background: Papillary thyroid cancer or papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The fact that it occasionally occurs in women aged 30-40 years old suggests that genetic alterations are involved its genesis. Recently, activator mutations in BRAF gene have been relatively frequently discovered. Materials and Methods: In this study, we tested 63 DNA samples from PTC patients to identify the V600E mutation frequency in the Ahvaz population. DNA was isolated from formalin fixed paraffin-embedded (FFPE) PTC tumor tissues. Genotyping was performed by PCR-RFLP and confirmed by direct DNA sequencing of a subset of PCR products. PCR-RFLP data were reported as genotype frequencies and percentages. Results: Forty nine out of 63 patients (77.8%) had a mutated heterozygote form while 14 (22.2%) showed normal genotype but none demonstrated a mutant homozygote genotype. The frequency of V600E mutation was significantly high in PTC patients. Conclusions: These findings support involvement of V600E mutations in PTC occurrence in Iran. Assessment of correlations between BRAF V600E mutations and papillary thyroid cancer progression needs to be performed.

• Journal of Genetic Medicine
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• 제11권2호
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• pp.63-68
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• 2014

Purpose: The mutation of the SLC26A4 gene is the second most common cause of congenital hearing loss after GJB2 mutations. It has been identified as a major cause of autosomal recessive nonsyndromic hearing loss associated with enlarged vestibular aqueduct and Pendred syndrome. Although most studies of SLC26A4 mutations have dealt with hearing-impaired patients, there are a few reports on the frequency of these mutations in the general population. The purpose of this study was to evaluate the prevalence of SLC26A4 mutations that cause inherited deafness in the general Korean population. Materials and Methods: We obtained blood samples from 144 Korean individuals with normal hearing. The samples were subjected to polymerase chain reaction to amplify the entire coding region of the SLC26A4 gene, followed by direct DNA sequencing. Results: Sequencing analysis of this gene identified 5 different variants (c.147C>G, c.225G>C, c.1723A>G, c.2168A>G, and c.2283A>G). The pathogenic mutation c.2168A>G (p.H723R) was identified in 1.39% (2/144) of the subjects with normal hearing. Conclusion: These data provide information about carrier frequency for SLC26A4 mutation-associated hearing loss and have important implications for genetic diagnostic testing for inherited deafness in the Korean population.

• Toxicological Research
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• 제29권3호
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• pp.217-219
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• 2013

Hypertension is a serious health problem due to high frequency and concomitant other diseases including cardiovascular and renal dysfunction. Olmesartan cilexetil is a new antihypertensive drug associated with angiotensin II receptor antagonist. This study was conducted to evaluate the mutagenicity of olmesartan cilexetil by bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA). At the concentrations of 0, 62, 185, 556, 1667, and 5000 ${\mu}g$/plate, olmesartan cilexetil was negative in both Salmonella typhimurium and Escherichia coli regardless of presence or absence of metabolic activation system (S9 mix). These results demonstrate that olmesartan cilexetil does not induce bacterial reverse mutation.

• KSBB Journal
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• 제9권1호
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• pp.16-25
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• 1994

Bacillus subtilis를 재조합 이종 단백질 생산 균주로 만들기 위하여 포자형성 변이주를 만들었다. 균주는 두 개의 프로테아제가 제거된 균주인 DB104로부터 spoOJ와 spoIIG 변이주를 유전자 조작법에 의해 만들고 두 개의 유전자가 모두 제거된 균주도 만들었다. 이에 목적 aprE 유전자를 삽입 벡터 형태로 만들어 integration시킨 뒤 변이주 각각의 형태적인 변화를 투과성 전자현미경으로 살펴 보았다. 각각 변이주의 모습은 이전에 보고된 것과 거의 일치하였으며 spoOJ spoIIG 이중포자변이주의 경우는 spoIIG 변이주와 더욱 닮은 것을 알 수 있었으며, 훨씬 주름진 것과 같은 투박한 세포벽 및 막을 가지고 있음을 관찰하였다. spoOJ 변이는 포자형성 빈도를 낮추고 aprE 활성을 감소시키는 반면, spoIIG 변이는 포자형성을 거의 하지 않으면서 aprE 활성에 상승효과를 가져왔다. spoOJ와 spoIIG 이중포자변이주는 spoOJ 변이의 효과는 거의 나타나지 않은채, spoIIG와 비슷한 aprE 활성을 보였다.

• Nuclear Engineering and Technology
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• 제13권3호
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• pp.161-167
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• 1981

자주달개비(Tradescantia) BNL clone 4430을 본 연구소 감마농장(${\gamma}$-field)에 거리별로 배치하고 ${\gamma}$-선을 3.6mR/day~182R/day의 선량율로 완조사시켜, 이 식물의 수술털에 나타나는 분홍색 체세포돌연변이를 대상으로 돌연변이의 출현율을 조사하는 한편 화기에 미치는 형태변화를 조사하였다. 분홍색 체세포돌연변이율은 22.2R/day의 선량율에서 수술털 1,000개당 85.81$\pm$6.45개로 가장 높았고, 이보다 높은 선량율에서는 오히려 변이율이 감소하여 포화선량효과를 초래하였다. 또한 3.6mR/day의 낮은 선량율체서도 이 체세포돌연변이율이 자연돌연변이율보다 증가하였음을 볼 수 있었으며 비교적 낮은 선량율 조사에서는 꽃, 수술, 수술털등의 형태적 변화가 없이 돌연 변이율만의 증가를 볼수가 있어 감마농장내에서 과수나 화목등 영년식물에 저선량의 완조사를 통해 체세포돌연변이의 유기가 가능할것으로 보이며, 한편 이 식물의 특성을 이용하여 저위 방사선에 의한 유전적변화를 탐지하는데에도 적절한 수단이 될 것 같다.

• Journal of Genetic Medicine
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• 제10권2호
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• pp.124-127
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• 2013

Among cause of carcinogenesis, heredity is believed to take about 10 percent in ovarian cancer. BRCA1 or BRCA2 account for largest portion of Hereditary Breast and Ovary Cancer (HBOC). Frequency of BRCA1/2 germ line mutations varies according to region and ethnicity from 1.1-39.7 percent. The identification of ovarian cancers with a BRCA mutation is will be more and important due to the possibility to offer a genetic counseling and also due to potential beneficial treatment effects with a poly-ADP-ribose polymerase inhibitor in some individuals. We report the case of a 41 year old woman with a stage Ic mucinous ovarian adenocarcinoma and carrier daughter found on family genetic counseling. We indentified other family members with a history of breast cancer of 1st degree and pancreatic cancer of 2nd degree relative. After a screening with immunohistochemistry, the absence of nuclear expression for BRCA1 and BRCA2 was revealed. The gene sequencing confirmed heterozygous mutations of BRCA2 gene. The daughter of the case subject consented for a test. This test was shown the daughter is positive for BRCA2 mutation. Regular surveillance, chemoprophylaxis with oral contraceptive and prophylactic surgery after childbearing were offered to her.