• Title/Summary/Keyword: Genetic Factors

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Molecular Application in Psychiatry (정신과의 분자생물학 적용)

  • Choi, Ihn-Geun
    • Korean Journal of Biological Psychiatry
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    • v.7 no.2
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    • pp.115-122
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    • 2000
  • The development of molecular biology has brought many changes in psychiatry. Molecular biology makes us possible to know the cause of mental disorders that provide the way to prevent the disorders, and to develop various accurate diagnostic and treatment methods for mental disorders. The author discusses the concept, cause, and treatment of mental disorders in the aspect of molecular biology. Importing the methods of molecular biology into psychiatry, we can anticipate to get a number of the goals of psychiatric genetics, including identification of specific susceptibility genes, clarification of the pathophysiological processes whereby these genes lead to symptoms, establishment of epigenetic factors that interact with these genes to produce disease, validation of nosological boundaries that more closely reflect the actions of these genes, and development of effective preventive and therapeutic interventions based on genetic counseling, gene therapy, and modification of permissive or protective environmental influences. In addition to their capacity to accelerate the discovery of new molecules participating in the nervous system's response to disease or to self-administered drugs, molecular biological strategies can also be used to determine how critical a particular gene product may be in mediating a cellular event with behavioral importance. Molecular biology probably enables us discover the environmental factors of mental disorders and allow rational drug design and gene therapies for mental disorders, by isolation of gene products that facilitate a basic understanding of the pathogenesis of these disorders. A specific genetic linkage may suggest a novel class of drugs that has not yet been tried. With respect to gene therapy, the hypothetical method would use a gene delivery system, most likely a modified virus, to insert a functional copy of a mutant gene into those brain cells that require the gene for normal function.

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Genetic Variations in XRCC4 (rs1805377) and ATF6 (rs2070150) are not Associated with Hepatocellular Carcinoma in Thai Patients with Hepatitis B Virus Infection

  • Makkoch, Jarika;Praianantathavorn, Kesmanee;Sopipong, Watanyoo;Chuaypen, Natthaya;Tangkijvanich, Pisit;Payungporn, Sunchai
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.591-595
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    • 2016
  • The liver is one of the most common sites of cancer in the world, hepatocellular carcinoma (HCC) predominating. Chronic hepatitis B virus infection (CHB) is considered as an important potential risk factors for HCC. Different people have diverse responses to HBV infection regarding the likelihood of HCC development, and host factors such as single nucleotide polymorphisms (SNPs) might account for this. The present study was conducted to evaluate any association between SNP frequencies in two genes, XRCC4 (rs1805377) and ATF6 (rs2070150), and the risk of CHB and HCC development in Thai patients. The study covered 369 subjects including 121 HCC patients, 141 with chronic hepatitis B virus infection (CHB) and 107 healthy controls. With TaqMan real-time PCR, the results showed that no significant association between XRCC4 (rs1805377) and ATF6 (rs2070150) and risk of HCC in the Thai population. From this first study of the 2 polymorphisms and HCC in Thailand it can concluded that rs1805377 and rs2070150 polymorphisms may not be applicable as genetic markers in the Thai population for HCC assessment.

Methylenetetrahydrofolate Reductase Genetic Polymorphisms and Esophageal Squamous Cell Carcinoma Susceptibility: A Meta-analysis of Case-control Studies

  • Wen, Yuan-Yuan;Yang, Shu-Juan;Zhang, Jian-Xing;Chen, Xin-Yue
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.21-25
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    • 2013
  • Background: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. Methods: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). Results: 19 studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. Conclusions: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T.

Contributions of CYP2C9/CYP2C19 Genotypes and Drug Interaction to the Phenytoin Treatment in the Korean Epileptic Patients in the Clinical Setting

  • Lee, Soo-Youn;Lee, Seung-Tae;Kim, Jong-Won
    • BMB Reports
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    • v.40 no.3
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    • pp.448-452
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    • 2007
  • We examined the contribution of CYP2C9 and CYP2C19 genotypes and drug interactions to the phenytoin metabolism among 97 Korean epileptic patients to determine if pharmacogenetic testing could be utilized in routine clinical practice. The CYP2C9 polymorphism is a wellknown major genetic factor responsible for phenytoin metabolism. The CYP219 polymorphism, with a high incidence of variant alleles, has a minor influence on phenytoin treated Koran patients. Using a multiple regression model for evaluation of the CYP2C9 and CYP2C19 genotypes, together with other non-genetic variables, we explained 39.6% of the variance in serum phenytoin levels. Incorporation of genotyping for CYP2C9 and CYP2C19 into a clinical practice may be of some help in the determination of phenytoin dosage. However, because concurrent drug treatment is common in patients taking phenytoin and many environmental factors are likely to play a role in drug metabolism, these factors may overwhelm the relevance of CYP polymorphisms in the clinical setting. Further investigations with an approach to dose assessment that includes comprehensive interpretation of both pharmacogenetic and pharmacokinetic data along with understanding of the mechanism of drug interactions in dosage adjustment is warranted.

Replacement and Lifetime Production Traits: Effect of Non-genetic Factors and Sire Evaluation

  • Singh, S.;Khanna, A.S.;Singh, R.P.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.1
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    • pp.11-15
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    • 2002
  • The present investigation was undertaken to study the effects of non-genetic factors and association among replacement and lifetime production traits. The data on 542 Holstein Friesian cows maintained during 1975-98 at State Cattle Breeding Project, Sector III, Hisar, were utilized. The average sex-ratio, abnormal births, mortality, culling and replacement rates on total calf born and total female calf born basis were 51.62, 8.50, 17.52, 31.05, 22.78 and 51.41 per cent, respectively. The study revealed that a minimum of 4 to 5 progenies are required per cow over its lifetime to replace itself. It indicated that each cow should produce a minimum of 2 female calves during its life so as to replace herself before being lost. The least-squares means for productive herd life, longevity and lifetime production were $1439.32{\pm}87.64$ and $2419.18{\pm}8.25$ days and $11317.95{\pm}913.15kg$, respectively. The heritability estimates for all replacement traits were very low indicating that sire selection may bring no desirable change in these traits. Heritability estimates were $0.178{\pm}0.157$, $0.288{\pm}0.184$ and $0.096{\pm}0.195$ for corresponding lifetime production traits. Breeding values and ranking of sires were generated for replacement and lifetime production traits to estimate the rank correlations between these traits. Moderate desirable rank correlations were obtained between replacement rate and lifetime production traits indicating that sires proven on the basis of milk production are also expected to have better replacement rate.

Effect of Monothioglycerol on ROS Inhibition, Mitochondrial Activity, and DNA Integrity in Frozen-thawed Miniature Pig Sperm (Monothiolglycerol이 동결 융해 후 미니돼지 정자의 활성산소 억제, 미토콘드리아 활성 그리고 DNA Integrity에 미치는 영향)

  • Park, Soo-Jung;Kim, Dae-Young
    • Journal of Embryo Transfer
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    • v.28 no.3
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    • pp.265-271
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    • 2013
  • Cryopreservation and in vitro fertilization (IVF) protocols are important in genetic studies and applications to transgenic animals. Various studies about boar sperm cryopreservation have been studied for a long time. Those were about the use of extenders, the choice of sugars, the cooling and warming rates. The factors that influence the boar sperm are the dramatic changes in temperatures, osmotic and toxic stresses, and reactive oxygen species (ROS) generation. Among these factors, ROS generation is the main damage to DNA which is a principal genetic material and the most important for the practical applications. So we wondered whether ROS generation could be reduced. In previous study, monothioglycerol (MTG) was essential for the culture of embryo stem cells. Therefore we added MTG in the freezing extender based on lactose-egg yolk (LEY) with trehalose. For the assessment of the frozen-thawed sperm, we focused onmotility, membrane integrity and DNA damage. First, we used a computer-aided sperm analysis system for overall conditions of sperm such as motility and viability. Then we performed the sperm chromatin structure assay for DNA integrity and hypo-osmotic swelling test for membrane integrity. And our result showed the existence of MTG in the freezing extender caused less damage to DNA and higher motility in frozen-thawed boar sperm. Also we checked a relative antioxidant activity of MTG in modified Modena B extender. We concluded that this reagent can activate sperm mitochondria at MTG $0.2{\mu}M$, contribute to sperm motility and DNA integrity but there was no significant difference on membrane integrity. Also antioxidant activity of MTG in modified Modena B extender was proved.

Genome-wide Association Study of Integrated Meat Quality-related Traits of the Duroc Pig Breed

  • Lee, Taeheon;Shin, Dong-Hyun;Cho, Seoae;Kang, Hyun Sung;Kim, Sung Hoon;Lee, Hak-Kyo;Kim, Heebal;Seo, Kang-Seok
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.3
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    • pp.303-309
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    • 2014
  • The increasing importance of meat quality has implications for animal breeding programs. Research has revealed much about the genetic background of pigs, and many studies have revealed the importance of various genetic factors. Since meat quality is a complex trait which is affected by many factors, consideration of the overall phenotype is very useful to study meat quality. For integrating the phenotypes, we used principle component analysis (PCA). The significant SNPs refer to results of the GRAMMAR method against PC1, PC2 and PC3 of 14 meat quality traits of 181 Duroc pigs. The Genome-wide association study (GWAS) found 26 potential SNPs affecting various meat quality traits. The loci identified are located in or near 23 genes. The SNPs associated with meat quality are in or near five genes (ANK1, BMP6, SHH, PIP4K2A, and FOXN2) and have been reported previously. Twenty-five of the significant SNPs also located in meat quality-related QTL regions, these result supported the QTL effect indirectly. Each single gene typically affects multiple traits. Therefore, it is a useful approach to use integrated traits for the various traits at the same time. This innovative approach using integrated traits could be applied on other GWAS of complex-traits including meat-quality, and the results will contribute to improving meat-quality of pork.

Interspecific Hybrids from Wild $\times$ Cultivated Triticum Crosses - A Study on the Cytological Behaviour and Molecular Relations -

  • Bhagyalakshmi, Kari;Vinod, Kunnummal Kurungara;Kumar, Mahadevan;Arumugachamy, Samudrakani;Prabhakaran, Amala Joseph;Raveendran, Thondikulam Subramanian
    • Journal of Crop Science and Biotechnology
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    • v.11 no.4
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    • pp.257-262
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    • 2008
  • Genetic diversity of cultivated wheat is narrowing down and is increasingly becoming non-complacent in tackling new pathogenic races and adverse environmental situations. Wild relatives of wheat are rich repositories of beneficial genes that are capable of defying adverse situations. However, these wild species are not readily crossable with cultivated ones. The present study attempted to cross three wild wheat species as females with three cultivated species of varying ploidy to understand the intricate behaviour of hybrids in relation to cytology, morphology, and molecular recombination. Post-fertilization barriers caused hybrid recovery in wild species in contrast to cultivated species. Triticum monococcum did not produce hybrids in any of the crosses. Various degrees of chromosome anomalies and hybrid sterility were seen with hybrids of T. timopheevi and T. sphaerococcum. Cytoplasmic factors were suspected to add more to the abnormality. G genome from T. timopheevi could enhance more pairing between Band D of cultivated species. Precocity of certain chromosomes in laggard formation was evident, pointing towards evolutionary self balance of the genomes which prevented homeologous pairing. They are eliminated in hybrids. Molecular diversity clearly corroborated with genetic proximity of the species, which distinguished themselves by maintaining the genome homeology.

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Characteristics of Central Noradrenergic Nervous System Response in SHR to Stimulation of Central ${\alpha}_2-Adrenoceptor$ (중추 ${\alpha}_2$-수용체 자극에 대한 선천성 고혈압쥐의 중추 노르아드레날린성 신경계 반응의 특성)

  • Chung, Hye-Joo;Oh, Uh-Taek;Ko, Kwang-Ho
    • YAKHAK HOEJI
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    • v.33 no.6
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    • pp.333-338
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    • 1989
  • It has been postulated that abnormal characteristics of central noradrenergic nervous system has been implicated in the development and maintenance of hypertension in several modes of experimental hypertension including spontaneously hypertensive rats (SHR). In the present study, we attempt to determine if abnormal characteristics of central noradrenergic nervous system in SHR is caused by genetic factors or hypertensive phenomena by evaluating the changes of central adrenoceptors after long-term treatment of clonidine. Animals were divided into three groups; (1) 14 week-old SHR; (2) age-matched normotensive Wistar rats (NW); (3) DOCA-Salt induced hypertensive rats (DS). Clonidine (100 ug/kg) or vehicle was injected intraperitonealy twice a day for 15 days. Changes of ${\alpha}_1-$ and ${\alpha}_2-receptor$ desities following clonidine treatment were determiend in frontal corte, medulla oblongata and hypothalamus using 3H-WB4101 and 3H-clonidine, respectively. Densities of ${\alpha}_1$ and ${\alpha}_2-receptors$ following clonidine treatment were not changed in frontal cortex and medulla oblongate of SHR as well as DS, but increased in frontal cortex of NW and decreased in medulla oblongata of NW. On the other hand, densities of ${\alpha}_1-receptors$ were increased and densities of ${\alpha}_2-receptors$ were not changed in hypothalamus of SHR but densities of ${\alpha}_1-$ and ${\alpha}_2-receptors$ were decreased in hypothalamus of DS as well as NW. These results suggest that such differences in frontal cortex and medulla oblongata of SHR may be results of hypertensive phenomena whereas those in hypothalamus may be relevant to genetic factors of SHR.

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Epidemiologic Study in Patients with Congenital Cleft Lip and Palate (선천성 구순 구개열 환자에 대한 역학적 연구)

  • Baek Jin-woo;Jung Sung-uk;Choi Sun-hyu;Yun Hyung-jin;Lee Eui-seok;Yun Jung-ju;Jang Hyun-seok;Rim Jae-suk
    • Korean Journal of Cleft Lip And Palate
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    • v.7 no.1
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    • pp.17-24
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    • 2004
  • Cleft lip and palate are most common congenital defomity to affect the orofacial region. Cleft lip and palate are caused by abnormal development of primary and secondary palate. Its causative mechanism is not completely understood, but genetic and environmental factors play important roles. Lots of epidemiologic surveys have been done extensively about incidence, racial influence, sex ratio, parent age, associated syndrome and genetic factors. These researches are useful to dissolve many problems in prevention and treatment of cleft lip and palate. We performed epidemiologic survey of cleft lip and palate who visited the department of Oral and Maxillofacial Surgery, Guro hospital of Korea University from 1995 to 2004.

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