• 제목/요약/키워드: Genetic Relationships

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A study of Association of the H-FABP RFLP with Economic Traits of Pigs (돼지 H-FABP 유전자의 다형성 및 경제 형질과의 연관성 구명)

  • Choi, B.H.;Kim, T.H.;Lee, J.W.;Cho, Y.M.;Lee, H.Y.;Cho, B.W.;Cheong, I.C.
    • Journal of Animal Science and Technology
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    • v.45 no.5
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    • pp.703-710
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    • 2003
  • The purpose of this study was to detect association between genetic variation and economic trait in the porcine heart type fatty acid-binding protein gene as a candidate gene for the traits related with growth and meat quality in pigs. The H-FABP is a 15-kDa protein expressed in several tissues with high demand for fat metabolism such as cardiac and skeletal muscle and lactating mammary gland. H-FABP is small intracellular protein involved in fatty acid transport from the plasma membrane to the site of $\beta$-oxidation and/or triacylglycerol or phospholipid synthesis. In this study, H-FABP PCR-RFLP was performed in F$_2$ population composed of 214 individuals from an intercross between Korean Native Boars and Landrace sows. PCR products from two primer sets within H-FABP gene were amplified in 850bp and 700bp. Digestion of PCR products with the restriction digestion enzymes HaeⅢ and HinfⅠ, revealed fragment length polymorphisms(RFLPs). The genotype frequencies from H-FABP/HaeⅢ was .29 for genotype DD, .53 for genotype Dd, and .15 for genotype dd, respectively. The genotype frequencies of HH, Hh, and hh from H-FABP/HinfⅠ was .38, .41 and .20, respectively, in the population. Relationships between their genotypes and economic traits were estimated. In H-FABP/HaeⅢ locus, there were specific genotypes(Dd and dd) associated with economic traits such as body weights at 3, 5, 12, and 30 week of age (p〈.05 to .001). The ‘d’ allele was associated with gaining of body weight. In H-FABP/HinfⅠ locus, Genotypes of HH and Hh associated with growth traits such as body weights at 5, 12, and 30 week of age (p〈.05 or p〈.001) and back fat thickness, body fat including abdominal and trimmed fat (p〈.001) and intramuscular fat(p〈.05) The ‘H’ allele was positively associated with gaining of body weight and fatness deposition. In conclusion, a significant association of the H-FABP gene from its genetic variation was found on body weight, intramuscular fat and backfat thickness.

Cis-acting Replication Element Variation of the Foot-and-mouth Disease Virus is Associated with the Determination of Host Susceptibility (구제역바이러스의 숙주 특이성 결정에 연관되어있는 구제역바이러스 cis-acting replication element 변이 분석 연구)

  • Kang, Hyo Rin;Seong, Mi So;Ku, Bok Kyung;Cheong, JaeHun
    • Journal of Life Science
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    • v.30 no.11
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    • pp.947-955
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    • 2020
  • The foot-and-mouth disease virus (FMDV), a member of the Aphthovirus genus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. During replication of the FMDV RNA (ribonucleic acid) genome, FMDV-encoding RNA polymerase 3D acts in a highly location-specific manner. This suggests that specific RNA structures recognized by 3D polymerase within non-coding regions of the FMDV genome assist with binding during replication. One such region is the cis-acting replication element (CRE), which functions as a template for RNA replication. The FMDV CRE adopts a stem-loop conformation with an extended duplex stem, supporting a novel 15-17 nucleotide loop that derives stability from base-stacking interactions, with the exact RNA nucleotide sequence of the CRE producing different RNA secondary structures. Here, we show that CRE sequences of FMDVs isolated in Korea from 2010 to 2017 exhibit A and O genotypes. Interestingly, variations in the RNA secondary structure of the Korean FMDVs are consistent with the phylogenetic relationships between these viruses and reveal the specificity of FMDV infections for particular host species. Therefore, we conclude that each genetic clade of Korean FMDV is characterized by a unique functional CRE and that the evolutionary success of new genetic lineages may be associated with the invention of a novel CRE motif. Therefore, we propose that the specific RNA structure of a CRE is an additional criterion for FMDV classification dependent on the host species. These findings will help correctly analyze CRE sequences and indicate the specificity of host species for future FMDV epidemics.

Molecular Phylogenetic Study of the Endangered Land Snail Satsuma myomphala Based on Metallothionein Gene. (Metallothionein 유전자를 기초로 한 멸종위기 육상 달팽이 Satsuma myomphala (거제외줄달팽이) 의 분자계통학적 연구)

  • Sang, Min Kyu;Kang, Se Won;Hwang, Hee-Ju;Chung, Jong Min;Song, Dae Kwon;Min, Hye Rin;Park, Jie Eun;Ha, Hee Cheol;Lee, Hyun Jun;Hong, Chan Eui;Ahn, Young Mo;Park, So Young;Park, Young-Su;Park, Hong Seog;Han, Yeon Soo;Lee, Jun Sang;Lee, Yong Seok
    • The Korean Journal of Malacology
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    • v.32 no.4
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    • pp.263-268
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    • 2016
  • Metallothionein (MT) family of metal-binding proteins are involved in maintaining homeostasis and heavy metal poisoning. Recently, MT has been considered as a biomarker that can identify a particular species, very similar to the use of cytochrome oxidase I (COI) gene. Satsuma myomphala species of land snails have been reported from North-East Asia, including South Korea and Japan. In particular, the land snail species have been known from only a limited area of Geoje Island, Gyeongsangnam-do province of South Korea. Genetic studies of S. myomphala has been limited with only 6 nucleotide, 2 protein registered on the NCBI server. For elucidating the genetic information of S. myomphala, we conducted RNA sequencing analysis using Illumina HiSeq 2500 next-generation platform. We screened the MT gene from the RNA-Seq database to confirm the molecular phylogenetic relationship. After sequencing, the de novo analysis and clustering generated 103,774 unigenes. After annotation against PANM database using BLAST program, we obtained MT sequence of 74 amino acid residues containing the coding region of 222 bp. Based on this sequence, we found about 53 sequences using the BLAST program in NCBI nr database. Using ClustalX alignment, Maximum-Likehood Tree of MEGA program, we confirmed the molecular phylogenetic relationships that showed similarity with mollusks such as Helix pomatia and H. aspersa, Megathura crenulata.

Genetic Identification and Biochemical Characteristics of Edwardsiella Strains Isolated from Freshwater Fishes Cultured in Korea (내수면 양식 어류에서 분리된 Edwardsiella 속 균주들의 유전학적 동정 및 생화학적 특성)

  • Jang, Mun Hee;Kim, Keun-Yong;Lee, Yu Hee;Oh, Yun Kyung;Lee, Jeong-Ho;Song, Jun-Young
    • Journal of fish pathology
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    • v.33 no.2
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    • pp.111-118
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    • 2020
  • The genus Edwardsiella belonging to the family Enterobacteriaceae is a member of Gram-negative rod-shaped bacteria that cause disease in diverse aquatic organisms such as fish, amphibians and reptiles as well as avians and mammals including human throughout the world. This genus had been composed of three species, E. hoshinae, E. ictaluri and E. tarda, but recent researches erected two novel species, E. anguillarum and E. piscicida that were conventionally identified as E. tarda. In this study, we isolated seven strains belonging to the genus Edwardsiella from freshwater fishes that had been reared at inland fish farms in South Korea and investigated their biochemical characteristics and molecular phylogenetic relationships. The seven strains showed typical characteristics of four Edwardsiella species, E. anguillarum, E. ictaluri, E. piscicida and E. tarda, by biochemical analyses of Gram staining, indole and hydrogen sulfide (H2S) production, and API (Analytic Profile Index) 20E test. Molecular phylogenetic analyses inferred from DNA sequence data of both 16S ribosomal RNA (rRNA) and DNA gyrase subunit B (gyrB) genes were congruent with the biochemical characteristics. As a result, both biochemical and molecular phylogenetic analyses identified four strains isolated from three Anguilla species as E. anguillarum, E. piscicida and E. tarda, two strains from Pelteobagrus fulvidraco and Silurus asotus as E. ictaluri, and one strain from Moroco oxycephalus as E. piscicida. In this study, we isolated and successfully identified recently newly erected species, E. anguillarum and E. piscicida in addition to historically notorious pathogenic species, E. ictaluri and E. tarda. In the future study, systematic and comprehensive monitoring of the four Edwardsiella species are required for studying differences in pathogenicity among freshwater fishes.

The Effects of Monoamine Oxidase A CA Repeat Polymorphism on Behavioral Trait and Clinical Characteristics in Korean Male Alcoholics (단가아민 산화제 A CA 반복 유전자 다형성이 한국 알코올의존 남자환자의 행동특성과 임상양상에 미치는 영향)

  • Lee, Jung-Sik;Yang, Byung-Hwan;Lee, Kyung-Mee;Kim, Hong-Kwan;Kim, Yong-In;Chai, Young-Gyu
    • Korean Journal of Biological Psychiatry
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    • v.7 no.1
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    • pp.64-73
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    • 2000
  • There are several candidate genes in genetic study of alcoholism. Among them, allelic associations have been reported between MAOA CA repeat polymorphism and alcohol dependence, recently. And also, several studies have been investigated genotype-phenotype relationships between MAOA CA repeat polymorphism and clinical manifestations. The authors tried to identify differences in allelic frequency of MAOA CA repeat polymorphism between alcohol dependence and controls, and in behavioral trait and clinical characteristics according to MAOA CA repeat polymorphism. We also tried to investigate genotype-phenotype relationships between MAOA CA repeat polymorphism and behavioral trait such as aggression. We examined 49 male patients with alcohol dependence(DSM-IV) who had been admitted in Yong-In Mental Hospital from June 1st 1998 to October 31th 1998. We performed semistructured interview for demographic and clinical characteristics. Self-report questionnaire for BDHI(Buss-Durkey Hostility Inventory) was given to all subject at least 4weeks later after admission. Using polymerase chain reaction and polyacrylamide gel electrophoresis, MAOA CA repeat polymorphism were observed in 52 male controls and 49 male patients with alcohol dependence. We devided alcoholic patients into two groups according to allelic length of MAOA CA repeat polymorphism ; alcoholics with short alleles(${\leq}$119bp, N=20) and alcoholics with long alleles(${\geq}$123bp, N=29). T-test, ${\chi}^2$-test and Fisher exact probability test were used for statistical analysis. There were no significant differences in frequency of each allele and short and long alleles of MAOA CA repeat polymorphism between alcoholics and controls. But there were significant differences in clinical symptoms and behavioral trait between alcoholics with short and long alleles. In clinical symptoms, alcoholics with long alleles used alcohol more frequently during one month before admission, had much more maximum amount of beer drinking and reported withdrawal seizure more frequently than with short alleles. In contrary, alcoholics with short alleles expressed depressed mood and guilty feeling more frequently and wanted complete abstinence as a treatment goal more frequently than with long alleles. In behavioral trait, alcoholics with long alleles had higher total aggression score and showed much more self-assertive attitude(subscale of expression of aggression) than with short alleles. Allelic length of MAOA CA repeat polymorphism was correlated with self-assertive attitude and accounted for 9% of the variance of self-assertive attitude. And also, predictable variables of allelic length of MAOA CA repeat polymorphism were drinking frequency and self-assertive attitude. Our findings suggest that MAOA CA repeat polymorphism may provide some behavior modifying role especially in self-assertive attitude and indirect symptom modifying role in Korean male alcoholics.

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Phylogenetic Relationships of Jeju Dogs to Other Domestic and Foreign Dog Breeds Determined by Using mtDNA D-loop Sequences (mtDNA D-loop의 염기서열에 의한 제주견과 우리나라 재래견 및 외국견품종과의 유연관계)

  • Kim, Mi-Gyoung;Kim, Nam-Young;Lee, Sung-Soo;Kim, Ky-IL;Yang, Young-Hoon
    • Journal of Animal Science and Technology
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    • v.53 no.4
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    • pp.303-310
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    • 2011
  • Phylogenetic relationships of Jeju dogs to other domestic and foreign dog breeds were assessed using mtDNA D-loop sequences. Neighbor-joining trees were constructed using complete sequences (970 bp excluding the tandem repeat region) determined for five Cheju, four Jindo, four Sapsaree, five Pungsan, two of each East and West Laika dogs (Canis familiaris), two gray wolves (Canis lupus) and two coyotes (Canis latrans) and also published complete sequences for dogs. Coyote sequences were used as outgroups. In addition, a total of 214 haplotypes of 598bp D-loop sequences from 30 dog breeds were collected from GenBank and used to investigate genetic structure of population. In the analyses of full D-loop sequence variation and the phylogenetic trees constructed by neighbor-joining method, neither haplotypes nor clades specific for any domestic dog breeds were observed. The inter-species sequence variation (4.51%) between domestic dogs and wolves was much higher than the intra-species sequence variation within domestic dogs (1.63%) and wolves (3.64%). The divergence of the dog and wolf occurred approximately 1~2 million years ago based on these values. The taxa of Jeju dog breed in the phylogenetic tree are clustered separately and intermingled with other taxa of breeds, suggesting that active crossbreeding of Jeju dogs with other domestic breeds.

A Study of the Distribution of Listeria spp. in Fresh Agricultural Products Distributed in the Busan Area, the Republic of Korea (부산지역에서 유통되는 신선농산물 중 리스테리아균 분포에 관한 연구)

  • Youn-ju Ok;Young-hee Kwon;Hye-sun Hwang;Ye-jee Byun;Ji-young Park;Byung-jun Kim
    • Journal of Food Hygiene and Safety
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    • v.39 no.1
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    • pp.9-15
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    • 2024
  • This study was performed to survey the distribution of Listeria spp. in fresh agricultural products in the Busan area, the Republic of Korea, from January to November 2022. We investigated the pathogenicity and epidemiological relationships by tracing isolated strains using polymerase chain reaction and pulsed-field gel electro-phoresis (PFGE) methods. Forty cases of Listeria spp. were detected in the 210 samples of fresh agricultural products analyzed. Four species, Listeria rocourtiae, L. innocua, L. grayi, and L. monocytogenes were detected only in green vegetables (lettuce, perilla leaps) and the others (L. innocua, L. monocytogenes, and L. grayi) were detected in enoki and oyster mushrooms. L. innocua was detected in 22 samples and L. grayi in six samples. L. monocytogenes, which causes foodborne diseases, was only detected in enoki mushrooms and the strains that were isolated had genes responsible for the pathogenicity of listeriosis (iap, prfA, inlA, inlC, inlJ, and hly). To investigate the genetic similarity and contamination route of L. monocytogenes, serotyping and PFGE were conducted for 12 strains isolated from fresh agricultural (10 strains) and poultry (2 strains) products distributed at a market in the Busan area. Two serotypes (1/2a, 1/2b) were detected in strains isolated from the agricultural and poultry products, but serotype 1/2b was only detected in strains isolated from agricultural products. PFGE analysis showed index of similarity values of 45.7 to 100% and the same patterns were represented in isolates from some enoki mushrooms. These isolates had the same serotypes and showed significant epidemiological relationships.

Studies on Genetic Analysis by the Diallel Crosses in $F_2$ Generation of Cowpea(Vigna sinensis savi.) (동부 Diallel Cross$ F_2$세대의 유전분석에 관한 연구)

  • Kim, J.H.;Ko, M.S.;Chang, K.Y.
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.28 no.2
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    • pp.216-226
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    • 1983
  • Genetic studies on the $F_2$ generation of a set of half diallel crosses involving six cowpea varieties were conducted. by the randomized block design with three replications to determine combining ability, gene action and the relationships between parents and their $F_2$ hybrids. The 12 agronomic characters namely, days to flowering, days from flowering to maturity, days to maturity, diameter of stem, length of internode, number of branches per plant, length of pod, number of pods per plant, number of grains per pod, number of grains per plant, 100 grain weight and grain weight per plot were observed, and the $F_2$ generation of this diallel set of crosses was analysed for each character according to the method by Jinks and Hayman. The results obtained are summarized as follows: 1. Vr-Wr graphical analyses; The following seven characters, days to flowering, number of branches per plant, length of pod, number of pods per plant, number of grains per plant, 100 grain weight and grain weight per plot appeared to be partially dominant, and over dominance was found for days from flowering to maturity, days to maturity, length of internode and number of grains per pod. But diameter of stem indicated partial dominance near complete dominance. 2. Estimates of genetic variance components; In the degree of dominance,. eight characters, that is, days to flowering, days from flowering to maturity, days to maturity, length of internode, number of pods per plant, number of grains per pod, number of grains per plant and grain weight per plot were expressed larger than 1. And the characters, days from flowering to maturity, number of branches per plant and number of grains per plant as the degree of mean dominance ($H_1$/D) were found to be negative value over other characters. On the other hand, apprent asymmetry of dominance-recessive allele ($H_2$ /$4H_1$) produced comparatively estimates with lower value on days from flowering to maturity, length of internode, number of branches per plant and number of grains per pod. 3. Analyses of combining ability; Mean square value of GCA(general combining ability) appeared to be more important than those of SCA (specific combining ability) for most characters, and among them, grain weight per plot showed the highest mean square value in GCA and SCA. 4. Effect of combining ability; Variety 178 was expressed as the highest GCA effects in five characters (days to flowering days to maturity, number of pods per plant, number of grains per plant and grain weight per plot). SCA effects were differed from parents, characters and crosses, but crosses between TVu 1857 $\times$ TVu 2885 and TVu 2702 $\times$ J78 were shown to be highly with SCA effects on yield.

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Studies on the Inheritance of Agronomic Characteristics in Upland Cotton Varieties (Gossypium hirsutum L.) in Korea (육지면품종의 유용형질의 유전에 관한 연구)

  • Bang-Myung Kae
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.21 no.2
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    • pp.281-313
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    • 1976
  • To obtain fundamental informations on cotton breeding efficiences for Korea, individual genetic relationships and interrelationships between the agronomic characteristics of Upland cotton were investigated. These experiments were couducted at the Mokpo Branch Station $(34^{\circ}48'N, $ $126^{\circ}23'E$ and altitude of 10m above sea level) from 1969 through 1972. Heterosis, combining ability, dominance and recessive gene action, genetic variance, and phenotypic and genotypic correlation were investigated by $F_1'S$ from an 11-parent partial diallel cross and the segregating $F_2$ and $F_3$ populations of the cross Paymaster times Heujueusseo Trice. The following points resulted from this study, 1. Heteroses for number of bolls per plant and lint yield were significant at 27, 84% and 37.26%, respectively. No other character had significant heteroses. 2. The GCA estimates for all studied characteristics were higher than the SCA estimates. Varieties with high GCA effects were Suwon 1 for earliness, Paymaster and Arijona for high lint percent, and Arijona for long fiber, etc, 3. SCA estimates for lint yield varied widely in crosses with Mokpo 4, Mokpo 6 and Heujueusseo Trice. Those crosses with the highest SCA effects were combinations with large characteristics differences, Example of these crosses are Mokpo 4 times Acala 1517W, Mokpo 4 times D. P. L. and Heujueusseo Trice aud Paymaster. 4. Early-maturing varieties were completely dominant to late-maturing varieties in some combinations while other crosses gave intermediate phenotypes. These results suggest additive genetic action by multi-genes. Heujueusseo Trice, Mokpo 6, and Suwon 1 showed highest degree of dominance for earliness. 5. There were no significant trends for inheritance of weight of boll and 100 seeds weight. 6. Long staple was partially to completely dominant to short staple. Though there were single gene ratios the rate of dominance decreased in the $F_2$ and $F_3$ populations in the cross between the long staple variety Paymaster and the short staple variety Heujueusseo Trice. Diallel cross $F_1$ hybrids showed complicated allelic gene action for staple length. Various dominance degree were shown by varieties. 7. Number of bolls per plant indicated strong over-dominance and small non-allelic additive gene action. 8. Lint Yield was characterized by over-dominance and by multiple non-allelic-gene action. High-yielding varieties were dominant to low-yielding ones. However, the low-yielding variety Heujueusseo Trice showed over-dominance, indicating different reactions according to the varieties and combinations. 9. Broad sense heritability for days to flowering was 34-39% while narrow sense heritability was 11%. Large variations of individual plants caused by Korean climatic conditions cause this situation. Heritability estimates for weight of boll was 30% for broad sense and 22% for narrow sense. 10. Heritability estimates for staple length and lint percent were very high suggesting strong selection effects. 11. Narrow sense heritability estimates for number of bolls per plant was 30% in the diallel cross $F_1$ hybrids and 36% in the $F_2$ population of the special cross. Broad sense heritability was estimated at 67% suggesting that. 12. Heritability estimates for lint yield was low due to high over-dominance in the diallel cross $F_1$ hybrids. Heritability estimates for yield was low in the $F_1$ hybrids but high in the $F_2$ and $F_3$ populations. 13. Phenotypic and genotypic correlations between lint percent and days to flowering and between staple length and days to flowering were high in the $F_1, $ $F_2$ and $F_3$ populations. Late-maturing varieties and individuals had long staple and high lint percent in general. As the correlation between days to flowering and lint yield was extremely low, the two traits were considered independent of each other. Days to flowering and number of bolls per plant were negatively correlated in the $F_3$ population, indicating early-maturing individual plants with many bolls may be readily selected. 14. Phenotypic and genotypic correlations between lint percent and staple length were high in $F_1, $ $F_2$ and $F_3$ populations. Accordingly, long staple varieties were high in lint percent. It was recognized that lint yield and lint percent were positively correlated in the diallel cross $F_1$ hybrids, and lint percent and staple length were positively correlated in the $F_2$ population, indicating that lint percent and staple length affect lint yield. 15. Lint yield was significantly and positively phenotypically correlated with number of bolls per plant in $F_1, $ $F_2$ and $F_3$ populations. A high genotypic correlation was also noted indicating a close genetic relationship. The selection efficiencies for a high-yielding variety can be increased when individual plants with many bolls are selected in later generations. The selection efficiencies for good fiber quality can be enhanced when individuals with long staple and high lint percent are selected in early generations.

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Genetic Polymorphisms of the $\beta_2$-Adrenergic Receptor in the Severity of Bronchial Asthma (기관지 천식 환자에서 천식 증상의 정도에 따른 $\beta_2$ 교감신경 수용체의 유전자 다형성)

  • Shim, Jae-Jeong;Kim, Jei-Hyung;Lee, Seung-Yong;Kwan, Young-Hwan;Lee, So-Ra;Lee, Sang-Youb;Kang, Se-Yong;Kang, Yong-Koo;Cho, Jae-Youn;In, Kwang-Ho;Won, Nam-Hee;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.1
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    • pp.77-89
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    • 1998
  • Background: Genetic and environmental factors are known to affect the incidence and severity of asthma. Stimulation of $\beta_2$-Adrenergic Receptor ($\beta_2$AR) results in smooth muscle relaxation, leading to decrease in resistance of airflow. The gene encoding the $\beta_2$AR has recently been seguenced. The $\beta_2$AR genotype at the polymorphic loci of codons 16, 27, 34, and 164 was known to cause changes in the amino acids. The relationships between the structure of the $\beta_2$AR and its functions are being elucidated. Purpose : The gene encoding the $\beta_2$AR was carried out to assess the frequency of polymorphisms in bronchial asthma, to determine wheather these polymorphisms have any relation to the severity, or nocturnal symptoms in bronchial asthma. Methods: The subjects studied were 103 patients with bronchial asthma, which consisted of 30 mild episodic, 32 mild persistent, 17 moderate, and 24 severe asthma patients. The polymorphisms of the $\beta_2$AR gene were detected by mutated allele specific amplification (MASA) method at the codons 16,27,34, and 164. Results: The most frequent polymorphism was arginine 16 to glycine. The other two polymorphisms, valine 34 to methionine and glutamine 27 to glutamic acid occured in 11 and 6 patients respectively. The polymorphism of threonine 164 to isoleucine was not found in our enrolled patients. The homozygous polymorphism of $\beta_2$AR gene was found in only arginine 16 to glycine (12.6%). The heterozygous polymorphisms of $\beta_2$AR gene were in arginine 16 to glycine, valine 34 to methionine, and glutamine 27 to glutamic acid, as 65.1 %,10.7%, and 5.8% respectively in asthma patients. The presence of agrginine 16 to glycine heterozygous or/and homozygous polymorphism was associated in severe asthma (p=0.015), but there was no association between the other three polymorphisms and the severity of asthma. The frequency of the $\beta_2$AR gene polymorphisms was no relation in nocturnal asthma as compared with non-nocturnal asthma. Conclusion: The arginine 16 to glycine polymorphism of the $\beta_2$AR gene is the most frequently found in asthma patients and association with severe asthma. But there was no association between the polymorphism of the $\beta_2$AR gene and nocturnal asthma.

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