• Clinical and Experimental Reproductive Medicine
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• 제34권3호
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• pp.179-188
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• 2007

목 적: 본 연구에서는 삼핵산 반복서열 확장에 의해 발병하는 헌팅톤병, 척수소뇌성 운동실조증과 X-염색체 취약 증후군 등에 대한 착상전 유전진단을 시행하기 위한 전임상 검사에서 진단 방법을 최적화하는 과정을 통해 얻은 결과들에 대해 기술하고자 한다. 연구방법: 단일 림프구를 이용한 임상전 검사에서는 서로 다른 allele를 갖고 있는 환자의 단일 세포를 사용하였으며, 헌팅톤병과 척수소뇌성 운동실조증에서는 fluorescent semi-nested PCR 시행 후 fragment analysis를 수행하였다. X-염색체 취약 증후군의 경우 multiple displacement amplification (MDA) 방법을 이용한 whole genome amplification에서 얻어진 MDA 산물로 fluorescent PCR을 시도하였다. 결 과: 헌팅톤병의 경우 단일 림프구 시료 모두에서 CAG repeats 증폭에 성공하여 100.0%의 증폭성공률과 14.0% allele drop-out (ADO) rate를, 척수소뇌성 운동실조증의 경우 94.7%의 증폭성공률과 5.6%의 ADO rate을 나타내었다. X-염색체 취약 증후군의 경우 fluorescent semi-nested PCR 방법만으로는 단일 림프구 시료에서 CGG repeats이 증폭되지 않았지만, MDA 산물을 이용한 fluorescent PCR 결과 84.2%의 증폭성공률과 31.3%의 ADO rate을 얻을 수 있었다. 결 론: 본 연구를 통해 헌팅톤병과 척수소뇌성 운동실조증의 착상전 유전진단에는 fluorescent semi-nested PCR 방법의 적용이 가능함을 확인하였으며, X-염색체 취약 증후군의 경우에는 MDA를 이용한 fluorescent PCR 방법을 사용해야 함을 알 수 있었다. 유전자의 변이에 대한 분석이 쉽지 않은 단일 유전자 이상에 대한 착상전 유전진단의 경우 다양한 유전자 분석 방법을 이용한 단일 세포에서의 진단 방법의 최적화 연구가 필수적으로 선행되어야 할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6299-6303
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• 2012

Insulin-like growth factor-binding protein-3 (IGFBP3) has been identified as a putative tumor suppressor with multifunctional roles in the IGF axis. Recently, there have been a growing body of studies investigating the relation between the IGFBP3 A-202C polymorphism, circulating IGFBP3 and prostate cancer risk, but their outcomes varied leading to controversy. Hence, it is necessary to perform a meta-analysis covering all eligible studies to shed a light on the association of IGFBP3 A-202C and cancer risk. Finally, we included a total of 11 relevant articles between 2003 and 2010 covering 14 case-control studies including 9,238 cases and 8,741 controls for our analysis. Our results showed that A-202C was a marginal risk factor of prostate cancer (allele contrast: OR=1.08, 95% CI :1.01-1.16; dominant model: OR=1.11, 95% CI :1.01-1.22; heterozygote codominant model: OR=1.11, 95% CI :1.03-1.18; homozygote contrast: OR=1.19, 95% CI :1.03-1.37). Stratification analysis revealed that sample size and control source were two major heterogeneous meta-factors especially in the recessive model (source: Population-based control group :p=0.30,I2=16.7%, Hospital-based control group: p=0.20, I2=30.3%; sample size: Small: p=0.22,I2= 32.8%, Medium: p=0.09,I2=48%, Large p=0.60,I2=0.0%); However, contrary to previous findings, no significance was found in racial subgroups. No significant publication bias was found in our analysis. Considering the robustness of the results and the discrepancy among some studies, there might be some unsolved confounding factors, and further more critical large studies are needed for confirmation.

• Genomics & Informatics
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• 제6권1호
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• pp.18-28
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• 2008

Single nucleotide polymorphisms (SNPs) are the most abundant forms of human genetic variations and resources for mapping complex genetic traits and disease association studies. We have constructed a linkage disequilibrium (LD) map of chromosome 22 in Korean samples and compared it with those of other populations, including Yorubans in Ibadan, Nigeria (YRI), Centre d'Etude du Polymorphisme Humain (CEPH) reference families (CEU), Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) in the HapMap database. We genotyped 4681 of 111,448 publicly available SNPs in 90 unrelated Koreans. Among genotyped SNPs, 4167 were polymorphic. Three hundred and five LD blocks were constructed to make up 18.6% (6.4 of 34.5 Mb) of chromosome 22 with 757 tagSNPs and 815 haplotypes (frequency $\geq$ 5.0%). Of 3430 common SNPs genotyped in all five populations, 514 were monomorphic in Koreans. The CHB + JPT samples have more than a 72% overlap with the monomorphic SNPs in Koreans, while the CEU + YRI samples have less than a 38% overlap. The patterns of hot spots and LD blocks were dispersed throughout chromosome 22, with some common blocks among populations, highly concordant between the three Asian samples. Analysis of the distribution of chimpanzee-derived allele frequency (DAF), a measure of genetic differentiation, Fst levels, and allele frequency difference (AFD) among Koreans and the HapMap samples showed a strong correlation between the Asians, while the CEU and YRI samples showed a very weak correlation with Korean samples. Relative distance as a quantitative measurement based upon DAF, Fst, and AFD indicated that all three Asian samples are very proximate, while CEU and YRI are significantly remote from the Asian samples. Comparative genome-wide LD studies provide useful information on the association studies of complex diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.889-896
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• 2015

Matrix metalloproteinase-2 (MMP2) is an endopeptidase, mainly responsible for degradation of extracellular matrix components, which plays an important role in cancer disease. A single nucleotide polymorphism (SNP) at -1306 disrupts a Sp1-type promoter site. The results from the published studies on the association between MMP2 -1306 C>T polymorphism and cancer risk are contradictory and inconclusive. In the present study, a meta-analysis was therefore performed to evaluate the strength of any association between the MMP2 -1306 C>T polymorphism and risk of cancer. We searched all eligible studies published on association between MMP2 -1306 C>T polymorphism and cancer risk in PubMed (Medline), EMBASE and Google Scholar online web databases until December 2013. Genotype distribution data were collected to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) to examine the strength of the association. A total of 8,590 cancer cases and 9,601 controls were included from twenty nine eligible case control studies. Overall pooled analysis suggested significantly reduced risk associated with heterozygous genotype (CT vs CC: OR=0.758, 95%CI=0.637 to 0.902, p=0.002) and dominant model (TT+CT vs CC: OR=0.816, 95%CI=0.678 to 0.982, p=0.032) genetic models. However, allelic (T vs C: OR=0.882, 95%CI=0.738 to 1.055, p=0.169), homozygous (TT vs CC: OR=1.185, 95%CI=0.825 to 1.700, p=0.358) and recessive (TT vs CC+CT: OR=1.268, 95%CI=0.897 to 1.793, p=0.179) models did not show any risk. No evidence of publication bias was detected during the analysis. The results of present meta-analysis suggest that the MMP2 -1306 C>T polymorphism is significantly associated with reduced risk of cancer. However, further studies with consideration of different populations will be required to evaluate this relationship in more detail.

• 한국육종학회지
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• 제50권4호
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• pp.387-395
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• 2018

다산 등 15개의 통일형 벼 품종을 이용하여 mesotrione을 처리한 후 5일부터 다산 등 13개 품종들은 신엽에서 백화현상이 발생하였으나, 밀양154호와 수원382호는 백화현상이 발생하지 않아 저항성 품종으로 선발되었다. Mesotrione 처리 후 다산 등 13개 품종들의 초장 및 건물중 억제율은 밀양154호와 수원382호보다 더 높았으며 약량에 따른 억제율이 증가하였다. 한아름2호/밀양154호의 $F_2$ 집단을 이용한 유전분석 결과 저항성이 149개체, 감수성이 41개체로 이론적 분리비 3:1($X^2=1.19$, P=0.31)에 적합하여, mesotrione 저항성 관련 유전자는 1개의 우성유전자에 지배되는 것으로 나타났다. BSA방법을 이용하여 mesotrione 저항성 관련 유전자를 탐색한 결과, 2번 염색체의 10.2 Mb에 위치한 SSR marker RM1358과 RM3501을 선발하였다. Fine mapping을 위해 선발된 5개의 저항성 개체 중에서 $F_2-137$은 RM12921부터 RM3501까지 재조환이 일어났고, $F_2-76$은 RM324부터 RM5101까지 재조환이 일어났다. 따라서, mesotrione 저항성 관련 유전자는 RM3501과 RM324 사이인 10.2 Mb~11.4 Mb에 존재하며, RM3501과 RM324의 조환률이 각각 0.53%과 2.65%이므로, RM3501을 mesotrione저항성 유전자 DNA 연관 marker로 선발하였다. 다산 등 20개 통일형 품종 및 mesotrione에 저항성을 나타내는 자포니카 품종인 운광과 감수성인 통일형 한아름의 $BC_2F_2$ 집단을 이용하여 RM3501의 MAS 이용 가능성을 검토한 결과, mesotrione 저항성 선발 marker로 활용은 가능하나, 정확한 선발 maker로 활용하기 위해서는 추가적인 실험이 필요할 것으로 판단된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3503-3507
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• 2013

Background: Although the majority of investigations concerned with TP53 and its protein have focused on coding regions, recently a set of studies highlighted significant roles of regulatory elements located in p53 mRNA, especially 5'UTR. The wrap53${\alpha}$ transcript is one of those that acts as a natural antisense agent, forming RNA-RNA hybrids with p53 mRNA and protecting it from degradation. Materials and Methods: In this study, we focused on the mutation status of exon $1{\alpha}$ of the WRAP53 gene (according to exon 1 of p53) in 160 breast tumor tissue samples and conducted a bioinformatics search for probable miRNA binding site in the p53/wrap53 overlapping region. Mutations were detected, using single stranded conformation polymorphism (SSCP) and sequencing. We applied the miRBase database for prediction of miRNAs which target overlapping region of p53/wrap53 transcripts. Results: Our results showed all samples to have wild type alleles in exon 1 of TP53 gene. We could detect a novel and unreported intronic mutation (IVS1+56, G>C) outside overlapping regions of p53/wrap53 genes in breast cancer tissues and also predict the presence of a binding site for miR-4732-5p in the 5'UTR of Wrap53 mRNA. Conclusions: From our findings we propose designing further studies focused on overexpression of miRNA-4732-5p and introducing different mutations in the overlapping region of wrap53 and p53 genes in order to study their effects on p53 and its ${\Delta}N$ isoform (${\Delta}$40p53) expression. The results may provide new pieces in the p53 targeting puzzle for cancer therapy.

• Asian-Australasian Journal of Animal Sciences
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• 제33권5호
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• pp.770-777
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• 2020

Objective: This study was conducted to determine early hereditary endowment to establish a short-term feeding program. Methods: Hanwoo steers (n = 140) were equally distributed into four groups (35/group) based on genetic meat yield index (MYI) viz. the greatest, great, low, and the lowest at Jukam Hanwoo farm, Goheung. All animals were fed in group pens (5 animals/pen) with similar feed depending on the growth stage. Rice straw was provided ad libitum, whereas concentrate was fed at 5.71 kg during the growing period (6 to 13 mo) and 9.4 kg during the fattening period (13 to 28 mo). Body weight (BW) was measured at two-month intervals, whereas carcass weight was determined at slaughtering at about 31 months of age. The Affymetrix Bovine Axiom Array 640K single nucleotide polymorphism (SNP) chip was used to determine the meat quantity-related gene in the blood. Results: After 6 months, the highest (p<0.05) BW was observed in the greatest MYI group (190.77 kg) and the lowest (p<0.05) in the lowest MYI group (173.51 kg). The great MYI group also showed significantly (p<0.05) higher BW than the lowest MYI group. After 16 and 24 months, the greatest MYI group had the highest BW gain (p<0.05) and were therefore slaughtered the earliest. Carcass weight was significantly (p<0.05) higher in the greatest and the great MYI groups followed by the low and the lowest MYI groups. Back-fat thickness in the greatest MYI group was highly correlated to carcass weight and marbling score. The SNP array analysis identified the carcass-weight related gene BTB-01280026 with an additive effect. The steers with the allele increasing carcass weight had heavier slaughter weight of about 12 kg. Conclusion: Genetic MYI is a potential tool for calf selection, which will reduce the slaughter age while simultaneously increasing carcass weight, back-fat thickness, and marbling score.

• 한국가축번식학회지
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• 제23권4호
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• pp.303-311
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• 1999

본 연구는 정자세포로부터 분리된 genome 내 DNA를 PCR 기법으로 증폭시킨 후 random amplified polymorphic DNA(RAPD) 분석을 통해 무지개송어의 품종 내 유전적 특성과 변이성을 해석하고 품종의 특이 유전적 표지를 개발하기 위해서 수행되었다. 20 종류의 primer를 사용하여 RAPD 양상을 검색한 후 다형현상의 출현빈도와 band 수에 기초하여 이들 중 6개의 primer를 선정하여 이용하였다. 그 중에 4개의 primer는 17개의 RAPD marker를 나타내었고, 그중 primer 당 8개인 48개 (28%)의 band 가 다형성을 보여주었다. 6개의 primer 중 4개는 개체들 사이에 다형성을 나타내는 band를 나타내었다. Bandsharing 의 경우 연어와 비교될 만큼 무지개송어는 3개의 특이적인 DNA marker를 가지고 있었다 (2.3. 2.0 및 1.3kb). 같은 무작위 primer를 이용해서 나타난 개별적인 band는 단일 primer 가 무지개송어의 정자핵 DNA의 경우 적어도 3개의 독립적인 genome 내 다형성을 탐지해 낼 수 있다는 것을 제시하고 있다. 이러한 primer에 의해서 나타난 RAPD 다형성은 개체식별을 위한 유전적 표지인자로서 사용될 수 있는 가능성을 제시하였으며, RAPD-PCR은 많은 어종에서 다형현상을 밝혀내는 기술이라 할 수 있다. 본 연구는 RAPD marker가 풍부하고 재현성이 있으며 RAPD 다형성을 지닌 marker를 사용하여 이러한 중요한 양식대상어종에서 미래의 gene mapping과 MAS 를 위한 기초를 제공해 줄 수 있다. RAPD 다형성은 어류의 품종 분화를 위한 유전적 표지로서 유용한 것으로 결론지을 수 있을 것이다.

• Nutrition Research and Practice
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• 제9권1호
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• pp.79-86
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• 2015

BACKGROUND/OBJECTIVES: It is well-known that alcohol consumption is associated with stroke risk as well as with aldehyde dehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated with stroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specific associations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population. SUBJECTS/METHODS: We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and free of stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases of stroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selected a single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism of ALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baseline questionnaire. RESULTS: Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2 polymorphism increased stroke risk among men. The multivariate hazard ratio [95% confidence interval] of stroke was 2.02 [1.03-3.99] for the wild-type allele compared with the mutant alleles, but the association was attenuated after controlling for alcohol consumption. Combinations of the wild-type allele and other risk factors of stroke, such as old age, diabetes mellitus, and habitual snoring, synergistically increased the risk among men. Among women, however, the ALDH2 polymorphism was not associated with stroke risk. CONCLUSIONS: The prospective cohort study showed a significant association between a common ALDH2 polymorphism and stroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain more risk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiable risk factors of stroke.

• BMB Reports
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• 제38권1호
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• pp.77-81
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• 2005

The monocyte chemotactic protein-3 (MCP3), on chromosome 17q11.2-q12, is a secreted chemokine, which attracts macrophages during inflammation and metastasis. In an effort to discover additional polymorphism(s) in genes whose variant(s) have been implicated in asthma, we scrutinized the genetic polymorphisms in MCP3 to evaluate it as a potential candidate gene for asthma host genetic study. By direct DNA sequencing in twenty-four individuals, we identified four sequence variants within the 3 kb full genome including 1,000bp promoter region of MCP3; one in promoter region (-420T>C), three in intron (+136C>G, +563C>T, +984G>A) respectively. The frequencies of those four SNPs were 0.020 (-420T>C), 0.038 (+136C>G), 0.080 (+563C>T), 0.035 (+984G>A), respectively, in Korean population (n = 598). Haplotypes, their frequencies and linkage disequilibrium coefficients (|D'|) between SNP pairs were estimated. The associations with the risk of asthma, skin-test reactivity and total serum IgE levels were analyzed. Using statistical analyses for association of MCP3 polymorphisms with asthma development and asthma-related phenotypes, no significant signals were detected. In conclusion, we identified four genetic polymorphisms in the important MCP3 gene, but no significant associations of MCP3 variants with asthma phenotypes were detected. MCP3 variation/haplotype information identified in this study will provide valuable information for future association studies of other allergic diseases.