• Asian-Australasian Journal of Animal Sciences
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• 제31권6호
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• pp.775-783
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• 2018

Objective: The purpose of this study was to investigate the genetic effects of six keratin (KRT) genes on the wool traits of 418 Chinese Merino (Xinjiang type) (CMXT) individuals. Methods: To explore the effects and association of six KRT genes on sheep wool traits, The polymerase chain reaction-based single-strand conformation polymorphism (PCR-SSCP), DNA sequencing, and the gene pyramiding effect methods were used. Results: We report 20 mutation sites (single-nucleotide polymorphisms) within the six KRT genes, in which twelve induced silent mutations; five induced missense mutations and resulted in $Ile{\rightarrow}Thr$, $Glu{\rightarrow}Asp$, $Gly{\rightarrow}Ala$, $Ala{\rightarrow}Ser$, $Se{\rightarrow}His$; two were nonsense mutations and one was a same-sense mutation. Association analysis showed that two genotypes of the KRT31 gene were significantly associated with fiber diameter (p<0.05); three genotypes of the KRT36 gene were significantly associated with wool fineness score and fiber diameter (p<0.05), three genotypes of the KRT38 gene were significantly associated with the number of crimps (p<0.05); and three genotypes of the KRT85 gene were significantly associated with wool crimps score, body size, and fiber diameter (p<0.05). Analysis of the gene pyramiding effect between the different genotypes of the gene loci KRT36, KRT38, and KRT85, each genotype in a gene locus was combined with all the genotypes of another two gene loci and formed the different three loci combinations, indicated a total of 26 types of possible combined genotypes in the analyzed population. Compared with the other combined genotypes, the combinations CC-GG-II, CC-HH-IJ, CC-HH-JJ, DD-HH-JJ, CC-GH-IJ, and CC-GH-JJ at gene loci KRT36, KRT38, and KRT85, respectively, had a greater effect on wool traits (p<0.05). Conclusion: Our results indicate that the mutation loci of KRT31, KRT36, KRT38, and KRT85 genes, as well as the combinations at gene loci KRT36, KRT38, and KRT85 in CMXT have significant effects on wool traits, suggesting that these genes are important candidate genes for wool traits, which will contribute to sheep breeding and provide a molecular basis for improved wool quality in sheep.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1603-1609
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• 2014

Background: The response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median ranging from 6 months to 11.5 years. TP53 is associated with old age, chemotherapy resistance, and worse OS. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurring in a minority of patients, and conferring a worse OS. Materials and Methods: We performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n=10). TP53 PCR sequencing was performed using DNA from bone marrow smears. Analysis was accomplished using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. Results: Fewer than half of the patients harbored TP53 mutations (40%). There was no significant difference in OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trends toward improved survival among patients less than 60 (11 vs 4 months, p=0.09), Hispanics (8 vs 1 months, p=0.11), and those not harboring SNP P72R (8 vs 2 months, p=0.10). There was a significant improvement in survival among patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complex karyotype (8 vs 1 months, p=0.03). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). Conclusions: Our study confirms previous reports that poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53 mutations were relatively common, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validate these findings.

• 전자공학회논문지CI
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• 제49권2호
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• pp.123-133
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• 2012

본 논문에서는 DNA 시퀀스의 불법 복제 및 변이 방지와 개인 정보 침해 방지, 또는 인증을 위한 DNA 워터마킹에 대하여 논의하며, 변이에 강인하고 아미노산 보존성을 가지는 부호영역 DNA 시퀀스 기반 DNA 워터마킹 기법을 제안한다. 제안한 DNA 워터마킹은 부호 영역의 코돈 서열에서 정규 특이점에 해당되는 코돈들을 삽입 대상으로 선택되며, 워터마크된 코돈이 원본 코돈과 동일한 아미노산으로 번역되도록 워터마크가 삽입된다. DNA 염기 서열은 4개의 문자 {A,G,C,T}로 (RNA은 {A,C,G,U}) 구성된 문자열이다. 제안한 방법에서는 워터마킹 신호처리에 적합한 코돈 부호 테이블을 설계하였으며, 이 테이블에 따라 코돈 서열들을 정수열로 변환한 다음 원형 각도 형태의 실수열로 재변환한다. 여기서 코돈은 3개의 염기들로 구성되며, 64개의 코돈들은 20개의 아미노산으로 번역된다. 선택된 코돈들은 아미노산 보존성을 가지는 원형 각도 실수 범위 내에서 인접 코돈과의 원형 거리차 기준으로 워터마크에 따라 변경된다. HEXA와 ANG 시퀀스를 이용한 $in$ $silico$ 실험을 통하여 제안한 방법이 기존 방법에 비하여 아미노산 보존성을 가지면서 침묵 변이와 미스센스 변이에 보다 강인함을 확인하였다.

• Tuberculosis and Respiratory Diseases
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• 제70권1호
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• pp.21-27
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• 2011

Background: Although the gold standard method for research trials on epidermal growth factor receptor (EGFR) mutations has been direct sequencing, this approach has the limitations of low sensitivity and of being time-consuming. Peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping is known to be a more sensitive detection tool. The aim of this study was to compare the detection rate of $EGFR$ mutation and EGFR-tyrosine kinase inhibitor (TKI) responsiveness according to $EGFR$ mutation status using both methodologies. Methods: Clinical specimens from 112 NSCLC patients were analyzed for $EGFR$ mutations in exons 18, 19, 20, and 21. All clinical data and tumor specimens were obtained from 3 university hospitals in Korea. After genomic DNA was extracted from paraffin-embedded tissue specimens, both PNA-mediated PCR clamping and direct-sequencing were performed. The results and clinical response to $EGFR$-TKIs were compared. Results: Sequencing revealed a total of 35 (22.9%) mutations: 8 missense mutations in exon 21 and 26 deletion mutations in exon 19. PNA-mediated PCR clamping showed the presence of genomic alterations in 45 (28.3%) samples, including the 32 identified by sequencing plus 13 additional samples (6 in exon 19 and 7 in exon 21). Conclusion: PNA-mediated PCR clamping is simple and rapid, as well as a more sensitive method for screening of genomic alterations in $EGFR$ gene compared to direct sequencing. This data suggests that PNA-mediated PCR clamping should be implemented as a useful screening tool for detection of $EGFR$ mutations in clinical setting.

• Tuberculosis and Respiratory Diseases
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• 제58권1호
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• pp.11-17
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• 2005

연구배경 : 결핵의 발병에 유전적인 소인이 존재하며 숙주 면역 반응에 $IFN-{\gamma}$가 중요한 역할을 한다고 알려져 있다. 파종성 NTM 또는 BCG 감염증 환자에서 $IFN-{\gamma}$ 수용체 유전자 돌연변이가 밝혀져 있는데, 결핵 환자에서 $IFN-{\gamma}$ 수용체의 부분결핍 유무는 잘 알려져 있지 않았다. 방 법 : 2개 이상의 장기를 침범한 파종성 결핵 환자 6명을 대상으로 염기순서분석을 통해 $IFN-{\gamma}$ 수용체 1과 $IFN-{\gamma}$ 수용체 2의 부분결핍을 초래하는 유전자 이상이 있는지를 살펴보았다. 결 과 : $IFN-{\gamma}R1$의 부분결핍을 초래하는 I87T와 818delT 818del4, 818insA 그리고 $IFN-{\gamma}R2$의 부분결핍을 초래하는 R114C 돌연변이 등 기존에 보고된 유전자 이상은 발견되지 않았다. 결 론 : 본 연구의 대상인 6명의 파종성 결핵 환자에서 $IFN-{\gamma}$ 수용체의 부분결핍을 초래하는 유전자 이상은 발견되지 않았다.

• Pediatric Infection and Vaccine
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• 제16권2호
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• pp.199-204
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• 2009

목 적: 아데노바이러스 early region 3 (E3) 유전자 단백은 세포독성 세포와 다양한 싸이토카인이 매개하는 세포파괴를 저해하는 기능을 한다. 본 연구는 E3 유전자의 다양성이 아데노바이러스의 분자생물학적 다양성을 설명할 수 있는지 밝히기 위하여 시행되었다. 방 법: 1990년부터 2000년까지 10년 동안 서울대학교 어린이병원에서 하기도 감염증으로 치료받은 소아로부터 분리 된 3형 아데노바이러스 14 주를 대상으로 하여 E3 유전자의 변이와 유전체형과의 연관성을 분석하였다. 결 과: 3형 아데노바이러스의 E3 유전자는 표준 주(M15952)와 비교하여 98%의 일치도를 보였으며, 국내 분리 주간의 일치도는 98.7%이었다. 아미노산 서열의 변이는 20.1 kDa, 20.6kDa, truncated 7.7 kDa, 10.3 kDa, 14.9 kDa, 그리고 15.3kDa에 나타났다. 또한, 14 주 모두에서 truncated 7.7 kDa의 시작 코돈에 missense 변이가 있었으며, 58개(10주) 혹은 94개(4주)의 염기쌍이 소실되는 변이가 동반되었다. 유전체형에 따른 E3 유전자의 변이는 대개 유전체형에 특이하게 나타나 연관성이 높은 것을 알 수 있었다. 결 론: 3형 아데노바이러스 주의 면역기능 조절 유전자 E3의 다양성은 유전체형과의 연관성이 높은 것으로 나타났다.

• Molecules and Cells
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• 제22권3호
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• pp.343-352
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• 2006

Sialic acid is a sugar typically found at the N-glycan termini of glycoproteins in mammalian cells. Lec3 CHO cell mutants are deficient in epimerase activity, due to a defect in the gene that encodes a bifunctional UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). Sialic acid modification on the cell surface is partially affected in these cells. We have mutagenized Lec3 CHO cells and isolated six mutants (termed C2m) deficient in the cell surface expression of polysialic acid (PSA). Mutant C2m9 was partially defective in expression of cell-surface PSA and wheat germ agglutinin (WGA) binding, while in the other five mutants, both cell-surface PSA and WGA binding were undetectable. PSA expression was restored by complementation with the gene encoding the CMP-sialic acid transporter (CST), indicating that CST mutations were responsible for the phenotypes of the C2m cells. We characterized the CST mutations in these cells by Northern blotting and RT-PCR. C2m9 and C2m45 carried missense mutations resulting in glycine to glutamate substitutions at amino acids 217 (G217E) and 256 (G256E), respectively. C2m13, C2m39 and C2m31 had nonsense mutations that resulted in decreased CST mRNA stability, and C2m34 carried a putative splice site mutation. PSA and CD15s expression in CST-deficient Lec2 cells were partially rescued by G217E CST, but not by G256E CST, although both proteins were expressed at similar levels, and localized to the Golgi. These results indicate that the novel missense mutations isolated in this study affect CST activity.

• Radiation Oncology Journal
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• 제21권2호
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• pp.149-157
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• 2003

목적: 한국인 젊은 여성 유방암 환자에서 유방암 유전자 (BRCA)가 예후인자가 될 수 있는지 알아보기 위하여 본 연구를 시행하였다. 대상 및 방법: 대학병원에서 치료를 받은 환자 중에서 유방암이나 난소암의 가족력과 관계없이 40세 이하의 환자를 선택하였다. 환자의 나이는 18~40세이었고 중앙값은 34.5세이었다. 환자의 말초혈액에서 림프구를 모아 DNA를 추출하였으며 BRCA1과 BRCA2의 모든 염기 중에서 기능과 관계 있는 부위의 DNA를 직접염기서열 결정방식으로 검사하였다. 조직표본 검사가 가능한 환자는 면역화학조직검사를 시행하였다. 대상 및 방법: 60명의 환자 중에서 유방암 발생과 직접 관계가 있는 돌연변이가 11개(18.3%) 있었고(BRCA1 6명, BRCA2 5명), 의미를 알기가 곤란한 돌연변이가 7개 있었으며 반 수 이상의 돌연변이는 이제까지 보고되지 않은 것이었다. 그리고 대부분의 돌연변이 환자는 유방암이나 난소암의 가족력이 관찰되지 않았다. 유방암 유전자 돌연변이 환자는 한 명도 치료의 실패가 없었으며 한 면에서 반대측 유방암이 발생하였다. 7년 무병 생존율은 돌연변이 환자에서 50%, 돌연변이와 관계가 없는 환자에서 79%이었고 차이는 없었다. BRCA 관련 종양에서 에스트로젠, 프로제스테론 수용체 음성의 비율이 높았으며 조직학적 분화도가 낮았으나 예후는 비교대상에 비해 나쁘지 않았다. 결론: 한국의 젊은 여성 유방암 환자는 예후가 인자가 있어도 재발률이 낮았으며 유전자 돌연변이 이환율이 높았으나 암의 발현율은 상대적으로 낮은 것으로 추정되었다 이 결과를 확인하기 위해 더 많은 환자 집단과 오랜 추적기간의 연구가 필요하다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권8호
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• pp.1081-1085
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• 2017

Objective: Previously, we reported quantitative trait loci (QTLs) affecting backfat thickness (BFT) traits on pig chromosome 5 (SW1482-SW963) in an F2 intercross population between Landrace and Korean native pigs. The aim of this study was to evaluate glutamate receptor-interacting protein 1 (GRIP1) as a positional candidate gene underlying the QTL affecting BFT traits. Methods: Genotype and phenotype analyses were performed using the 1,105 $F_2$ progeny. A mixed-effect linear model was used to access association between these single nucleotide polymorphism (SNP) markers and the BFT traits in the $F_2$ intercross population. Results: Highly significant associations of two informative SNPs (c.2442 T>C, c.3316 C>G [R1106G]) in GRIP1 with BFT traits were detected. In addition, the two SNPs were used to construct haplotypes that were also highly associated with the BFT traits. Conclusion: The SNPs and haplotypes of the GRIP1 gene determined in this study can contribute to understand the genetic structure of BFT traits in pigs.

• Journal of Animal Science and Technology
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• 제54권6호
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• pp.411-418
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• 2012

KIT gene is the major causative gene for coat color variation in diverse animal species. This gene regulates melanocyte migration from the neural crest to target tissues and the mutation of this gene can affect dominant white phenotypes in animals. Because this gene has a major influence for the coat color variation, single nucleotide polymorphisms (SNPs) in 14 Korean cattle (Hanwoo) and 5 Holstein individuals were investigated. The Hanwoo DNA samples included three different colored (5 Black, 5 Yellow and 4 Stripe) animals. Total 126 polymorphisms have been identified and 23 of them are located in the exon region. Also, 5 bp (TTCTC) and 3 bp (TCT) intronic indels in intron 3 and intron 5, respectively, were identified. Out of 23 exonic polymorphisms, 15 SNPs are the missense mutations and the rest of the SNPs are silence mutations. The neighbor-joining phylogenetic tree was constructed for the different colored animals using the obtained KIT gene sequences. Holstein breed showed a clear breed-specific cluster in the phylogenetic tree which is differed from Hanwoo. Also, three colored Hanwoo animals were not discriminated among the breeds. The KIT gene polymorphisms identified in this study will possibly give some solutions for the color variations in cattle with further verifications.