• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3437-3441
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• 2012

Background: Oncogenic Bmi-1 (B-lymphoma Moloney murine leukemia virus insertion region-1) belongs to the Polycomb-group (PcG) family of proteins and plays an important role in the regulation of proliferation, senescence, cell cycle and apoptosis, chromosome stability, activation of gene transcription. Methods: To clarify the roles of Bmi-1 in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) and real-time RT-PCR in gastric carcinomas, dysplasia, intestinal metaplasia (IM), and gastritis with a comparison of its expression with clinicopathological parameters of carcinomas. Results: There was gradually increased Bmi-1 protein expression from gastritis, IM, dyplasia to carcinoma (p<0.001). Bmi-1 expression was positively linked to tumor size, depth of invasion, lymph node metastasis and worse prognosis of carcinomas (p<0.001), but not to age or sex of carcinoma patients (p>0.05). There was higher Bmi-1 protein expression in intestinal-type carcinomas than diffuse-type ones (p<0.001). At mRNA level, Bmi-1 protein expression was increased from gastritis, IM, dysplasia and carcinoma (p<0.001). Bmi-1 overexpression was observed in gastric carcinoma with larger diameter, deeper invasion, lymph node metastasis, and intestinal-type carcinoma (p<0.05). Conclusion: These findings indicate that up-regulated Bmi-1 expression is positively linked to pathogenesis, growth, invasion, metastasis and differentiation of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviors and prognosis of gastric carcinomas.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6403-6409
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• 2013

Purpose: Biallelic germline variants of the 8-hydroxyguanine (8-OG) repair gene MYH have been associated with colorectal neoplasms that display somatic $G:C{\rightarrow}T:A$ transversions. However, the effect of single germline variants has not been widely studied, prompting the present investigation of monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC) in a Chinese population. Patients and Methods: Between January 2006 and December 2012, 400 cases of sporadic CRC and 600 age- and sex-matched normal blood donors were screened randomly for 7 potentially pathogenic germline MYH exons using genetic testing technology. Variants of heterozygosity at the MYH locus were assessed in both sporadic cancer patients and healthy controls. Univariate and multivariate analyses were performed to determine risk factors for cancer onset. Results: Five monoallelic single nucleotide polymorphisms (SNPs) were identified in the 7 exon regions of MYH, which were detected in 75 (18.75%) of 400 CRC patients as well as 42 (7%) of 600 normal controls. The region of exon 1 proved to be a linked polymorphic region for the first time, a triple linked variant including exon 1-316 $G{\rightarrow}A$, exon 1-292 $G{\rightarrow}A$ and intron 1+11 $C{\rightarrow}T$, being identified in 13 CRC patients and 2 normal blood donors. A variant of base replacement, intron 10-2 $A{\rightarrow}G$, was identified in the exon 10 region in 21 cases and 7 controls, while a similar type of variant in the exon 13 region, intron 13+12 $C{\rightarrow}T$, was identified in 8 cases and 6 controls. Not the only but a newly missense variant in the present study, p. V463E (Exon 14+74 $T{\rightarrow}A$), was identified in exon 14 in 6 patients and 1 normal control. In exon 16, nt. 1678-80 del GTT with loss of heterozygosity (LOH) was identified in 27 CRC cases and 26 controls. There was no Y165C in exon 7 or G382D in exon 14, the hot-spot variants which have been reported most frequently in Caucasian studies. After univariate analysis and multivariate analysis, the linked variant in exon 1 region (p=0.002), intron 10-2 $A{\rightarrow}G$ (p=0.004) and p. V463E (p=0.036) in the MYH gene were selected as 3 independent risk factors for CRC. Conclusions: According to these results, the linked variant in Exon 1 region, Intron 10-2 $A{\rightarrow}G$ of base replacement and p. V463E of missense variant, the 3 heterozygosity variants of MYH gene in a Chinese population, may relate to the susceptibility to sporadic CRC. Lack of the hot-spot variants of Caucasians in the present study may due to the ethnic difference in MYH gene.

• Journal of Genetic Medicine
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• 제8권1호
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• pp.1-16
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• 2011

현재 사용되고 있는 침습적 산전진단법(양수천자, 융모막샘플링)은 1-2%의 태아 손실이 초래되어, 비침습적 산전진단법이 산전진단의 궁극적인 목표로 대두되어 왔다. 1997년 Dr. Lo에 의해서 임신부 혈장 내에 세포 유리 태아 DNA (cffDNA)의 존재가 발견된 후 비침습적 산전진단의 새로운 가능성이 열렸으며, 과거 10년간 이에 대한 연구의 많은 진전을 보여주고 있다. 최근에 cffDNA를 이용한 Hemophilia A와 듀센형 근이영양증 등 반성 유전병(X-linked disorders) 진단에 필수적인 산전태아의 성 판정과 RhD-음성 임신부에서 태아의 RhD유전자 핵형 분석 등이 이미 외국에서 임상적으로 적용되고 있으나, 한국에서는 아직 실용화되지 않고 있다. CffDNA의 임상 사용에는 여전히 많은 제약점이 있으며, 이는 임신부 혈장 내 cffDNA 양에 비해 많은 양의 모태 DNA가 존재하고, 종래에 사용되었던 특이적인 Y염색체 유전자(Y-specific gene)는 남아 태아 임신 시에만 적용된다는 것에 기인한 다. 따라서 모든 태아에 적용할 수 있는 태아 성과 무관한 마커(sex-independent universal fetal marker as internal positive controls)가 요구되며, 이를 이용하여 정확한 태아 DNA를 검출할 수 있다. 본 연구진은 국내 처음으로 임신부 혈장 내에 cffDNA를 이용하여 SRY 유전자, RhD-exon 7, 태아 성과 무관한 DNA마커(universal fetal DNA marker)로써 RASSF1A 유전자를 실시간 중합효소연쇄반응(RT- PCR)을 사용하여 뛰어난 결과를 얻었다. 이는 한국에서 처음으로 성공적으로 시도된 것이다. 연구결과에서 산전 태아 성 판별과 산후 태아의 성이 100% 일치하였으며, 임신 주기별 SRY 수치는 임신이 진행할수록 증가함을 확인할 수 있었다. 따라서 이러한 방법은 혈우병 A, 듀센형 근이영양증, 선천성 부신증식증과 연골 무형성증의 진단과 치료 상담에 이용할 수 있으며 50%에서 침습적인 방법을 줄일 수가 있다. 또한, RhD-음성 임신부 대상으로 태아의 성 판정과 RhD 태아 유전자형을 분석한 결과 RhD-음성 태아를 정확히 검출함으로써 앞으로 기존 양수천자 등 침습적 검사를 대체할 수 있을 것이다. 특히 이는 치료가 필요 없는 RhD-음성 태아에서 RhD-면역글로불린의 예방적 치료를 사전에 막을 수 있어, 임신부 건강을 보호하고 의료 비용을 줄일 수 있는 큰 장점을 가진다. 한국에서 최초로 시도된 임신부 혈장 내 cffDNA를 이용한 본 연구의 성공은 비침습적 산전진단 임상 적용의 새 길을 제시하였다. 따라서 이를 각 유전질환의 산전진단에 유용하게 활용하는 것은 태아와 임신부의 건강 증진과 의료비용 절약 등 개인과 국가에 많은 기여를 할 것으로 사료된다.

• Asian-Australasian Journal of Animal Sciences
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• 제24권4호
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• pp.463-470
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• 2011

Gonadotropin-releasing hormone receptor (GnRHR) gene is expressed at the anterior pituitary gland and plays a key role in gonad development. This study aimed to investigate molecular genetic characteristics of the GnRHR gene and elucidate the effects of single nucleotide polymorphisms (SNPs) of GnRHR gene on sex steroid level in Japanese flounder (Paralichthys olivaceus). We used polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and sequencing of the GnRHR gene in 75 individuals. We identified three SNPs in the GnRHR gene: P1 locus (C759A and C830T) in the coding region of exon2 which were both linked together and P2 locus (G984T) in the coding region of exon3, which added a new transcript factor (ADR1) and a new methylation site (CG). Only C830T of P1 leads to amino acid changes Thr266Ile. Statistical analysis showed that P1 was significantly associated with $17{\beta}$-estradiol ($E_2$) level (p<0.01) and gonadosomatic index (GSI) (p<0.05). Individuals with genotype BB of P1 had significantly higher serum $E_2$ levels (p<0.01) and GSI (p<0.05) than those of genotype AA or AB. Another SNP, P2, synonymous mutation, was significantly associated with GSI (p<0.05). Individuals with genotype AB of P2 had significantly higher GSI (p<0.05) than that of genotype AA. In addition, there was a significant association between one diplotype based on three SNPs and reproductive traits. The genetic effects for both serum $E_2$ level and GSI of diplotype D4 were super diplotypes (p<0.05). These results suggest that the SNPs in Japanese Flounder GnRHR are associated with $E_2$ level and GSI.

• 한국가금학회지
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• 제51권2호
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• pp.117-125
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• 2024

본 연구는 조우성과 만우성 닭을 식별하기 위한 유전자 마커를 발굴하고자 한 것으로 만우성과 관련된 ev21-K라는 새로운 좌위를 발견하고 이의 특성을 구명하였다. 더불어, 본 좌위의 유전적 전이 양상을 조사하여 자가 성감별 라인 조성의 이용 가능성도 살펴보았다. 본 시험을 위해 5개 품종의 닭 707수를 공시하고 이를 대상으로 유전자 마커 발굴 및 유전적 전이 시험을 수행하였다. ev21-K 특이 좌위 발굴은 깃털 발육과 연관된 ev21 유전자와 만우성 유전자인 K 유전자를 탐색하고 이들 간 염기서열을 비교 분석하여 획득하였다. 확인된 좌위의 분석을 위해 대상 서열에 대한 특정 프라이머를 제작하고 중합효소연쇄반응(PCR)을 수행하여 결과물을 획득한 후 이들의 염기 서열을 분석하였다. 발굴된 염기 서열의 유전적 전이 양상을 조사하기 위하여 조우성과 만우성 닭 간의 교배조합시험을 수행하였다. 시험결과, 발굴된 230 bp ev21-K 유전자 좌위를 ev21-related K specific sequences라 명명하였고, 이는 기존 ev21 유전자와 99%의 상동성을 나타내었다. PCR 분석을 통해 해당 서열이 만우성 닭에만 존재하는 것으로 확인되었다. 본 서열은 조직, 품종 및 연령에 관계없이 만우성 닭에만 존재하는 일관된 결과를 보여주었다. 교배 시험을 통하여 본 서열의 전이 양상을 살펴본 결과, 반성 유전을 하며 깃털 표현형과 일치하는 분리결과를 보였다. Ev21-related K specific sequences의 유전적전이 양상은 본 서열이 우성으로써 전형적인 멘델 유전에 따르는 것으로 나타났다. 결론적으로, ev21-K 특이 좌위의 새로운 서열은 품종에 관계없이 조우성과 만우성 닭을 식별하기 위한 신뢰할 수 있는 분자 마커로 확인되었다.

• Annals of Pediatric Endocrinology and Metabolism
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• 제23권4호
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• pp.220-225
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• 2018

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent $M{\ddot{u}}llerian$ duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

• 한국가금학회지
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• 제48권1호
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• pp.41-50
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• 2021

최근 병아리의 성 감별은 닭의 반성유전자를 이용한 깃털 감별법이 산업적으로 널리 이용되고 있으나, 한국토종닭에서는 아직 깃털 감별법이 활용되지 않고 있다. 따라서 본 연구에서는 한국토종닭의 깃털 감별의 산업적 적용을 위하여 닭의 조우성과 만우성 유전자를 이용한 자가성감별 계통을 조성하고자 한 것이다. 기초 계군으로 한국재래닭 적갈색종 557수를 대상으로 하여 조우성과 만우성의 유전자 빈도를 분석한 결과, 각각 0.814와 0.186으로 추정되어 본 집단으로 깃털자가성감별 계통의 구축이 가능한 것으로 판단되었고, 이를 바탕으로 조우성 부계통과 만우성 모계통의 종계 계군을 조성하였다. 모계통 조성에 이용할 만우성 동형접합체(KK) 수컷 선발을 위하여 검정교배를 실시한 결과 40수 중3수가 동형접합개체로 확인되었다. 조우성 종계와 만우성 종계 간의 생산능력을 비교하기 위하여 생존율, 체중, 초산일령, 산란율 및 난중을 분석한 결과, 조우성 닭은 생존율이 우수하였고, 만우성 닭은 산란율이 우수한 것으로 나타났으나, 다른 생산능력에서는 조우성과 만우성 닭 간에 차이가 없는 것으로 나타났다. 더불어 조성된 깃털 자가성감별 계통으로부터 생산된 병아리의 암수 감별의 유효성을 검정한 결과, 98.6%의 감별 일치율을 보였다. 따라서 한국토종닭을 이용한 깃털 자가성감별계통 조성 가능성과 더불어 이의 산업적 활용 가능성을 제시한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7169-7174
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• 2014

Background: NPAS2 is a product of the circadian clock gene. It acts as a putative tumor suppressor by playing an important role in DNA damage responses, cell cycle control and apoptosis. Chronic lymphocytic leukemia (CLL) appears to be an apoptosis related disorder and alteration in the NPAS2 gene might therefore be directly involved in the etiology of CLL. Here, the Ala394Thr polymorphism (rs2305160:G>A) in the NPAS2 gene was genotyped and melatonin concentrations were measured in a total of seventy-four individuals, including thirty-seven CLL cases and an equal number of age- and sex-matched healthy controls in order to examine the effect of NPAS2 polymorphism and melatonin concentrations on CLL risk in a Pakistani population. Materials and Methods: Genotyping of rs2305160:G>A polymorphism at NPAS2 locus was carried out by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Melatonin concentrations were determined by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistical Package for Social Sciences software. Results: Our results demonstrated no association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with risk of CLL. Similarly, no association of rs2305160 with CLL was observed in either females or males after stratification of study population on a gender basis. Moreover, when the subjects with CLL were further stratified into shift-workers and non-shift-workers, no association of rs2305160 with CLL was seen in either case. However, significantly low serum melatonin levels were observed in CLL patients as compared to healthy subjects (p<0.05). Also, lower melatonin levels were seen in shift-workers as compared to non-shift-workers (p<0.05). There was no significant difference (p>0.05) in the melatonin levels across NPAS2 genotypes in all subjects, subjects with CLL who were either shift workers or non-shift-workers. General Linear Model (GLM) univariate analysis revealed no significant association (p>0.05) of the rs2305160 polymorphism of the NPAS2 gene with melatonin levels in any of the groups. Conclusions: While low melatonin levels and shift-work can be considered as one of the risk factors for CLL, the NPAS2 rs2305160 polymorphism does not appear to have any association with risk of CLL in our Pakistani population.

• Asian-Australasian Journal of Animal Sciences
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• 제9권4호
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• pp.455-459
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• 1996

The genetic parameters for various economic traits were estimated in a White Leghorn population selected for part period egg production over 16 generations. In early part of selection, egg number had moderate to high heritability (0.26 to 0.51) while age at sexual maturity, egg weight and body weight at 20 and 40 weeks of age had high heritability (0.54 to 0.83). The sire component heritability for all the traits except 20 week body weight declined in later periods of selection. Sex linked gene effects for egg number and age at sexual maturity were more important in early periods of selection in comparison to the later periods, while maternal effects remained important for 20 week body weight in all the periods. Egg number was negatively correlated with egg weight ($r_{G(S)}=-0.36$), age at sexual maturity ($r_{G(S)}=-0.84$) and 40 week body weight ($r_{G(S)}=-0.84$), while it was positively correlated with 20 week body weight ($r_{G(S)}=-0.34$) in base generation. The genetic association between egg number and 40 week body weight changed not only in magnitude but also in direction in later periods. The genetic correlation of egg number with egg weight as well as with age at sexual maturity also decreased in magnitude in later periods of selection.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.27-31
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• 2012

Objectives: Expression of vascular endothelial growth factor C (VEGF-C)and vascular endothelial growth factor feceptor-3 (VEGFR-3) in laryngeal squamous carcinoma and its relationship to lymph node metastasis were investigated. Methods: VEGF-C and VEGFR-3 gene expression in 30 cases of normal laryngeal mucosa tissue (NLM), primary laryngeal carcinoma cell carcinomas (PLC) and cervical lymph nodes (CLN) was examined by reverse transcription polymerase chain reaction (RT-PCR). Protein levels of VEGF-C expression were determined by immunohistochemical staining in 60 cases of PLC. Results: Expression of VEGF-C and VEGFR-3 different among NLM, PLC and CLN in the same patient. In PLC, expression was significantly higher in lymph node positive group than in the lymph node negative group and associated with histological grade of differentiation; Expression of VEGF-C and VEGFR-3 was not linked with age, sex, site or T stage. Conclusions: A close correlation was found between VEGF-C/VEGFR-3 expression and lymph node metastasis in PLC, suggesting a role in metastasis of laryngeal carcinomas.