• Title/Summary/Keyword: Genetic interaction

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Molecular Dissection of the Interaction between hBLT2 and the G Protein Alpha Subunits

  • Vukoti, Krishna Moorthy;Lee, Won-Kyu;Kim, Ho-Jun;Kim, Ick-Young;Yang, Eun-Gyeong;Lee, Cheol-Ju;Yu, Yeon-Gyu
    • Bulletin of the Korean Chemical Society
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    • v.28 no.6
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    • pp.1005-1009
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    • 2007
  • Leukotriene B4 (LTB4) is a potent chemoattractant for leukocytes and considered to be an inflammatory mediator. Human BLT2 (hBLT2) is a low-affinity G-protein coupled receptor for LTB4 and mediates pertussis toxin-sensitive chemotactic cell movement. Here, we dissected the interaction between hBLT2 and G-protein alpha subunits using GST fusion proteins containing intracellular regions of hBLT2 and various Gα protein including Gα i1, Gα i2, Gα i3, Gα s1, Gα o1, and Gα z. Among the tested Gα subunits, Gα i3 showed the highest binding to the third intracellular loop region of hBLT2 with a dissociation constant (KD) of 5.0 × 10?6 M. These results suggest that Gα i3 has the highest affinity to hBLT2, and the third intracellular loop region of hBLT2 is the major component for the interaction with Gα i3.

Major gene interaction identification in Hanwoo by adjusted environmental effects (환경적인 요인을 보정한 한우의 우수 유전자 조합 선별)

  • Lee, Jea-Young;Jin, Mi-Hyun
    • Journal of the Korean Data and Information Science Society
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    • v.23 no.3
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    • pp.467-474
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    • 2012
  • Human diseases and livestock economic traits are not typically the result of variation of a single genetic locus, but are rather the result of interplay between interactions among multiple genes and a variety of environmental exposures. We have used linear regression model for adjusted environmental effects and multifactor dimensionality reduction (MDR) method to identify gene-gene interaction effect of statistical model in general. Of course, we use 5 SNPs (single uncleotide polymorphism) which were studied recently by Oh et al. (2011). We apply the MDR (multifactor demensionality reduction) method on the identify major interaction effects of single nucleotide polymorphisms responsible for economic traits in a Korean cattle population.

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

  • Md Tahsin Khan;Araf Mahmud;Md. Muzahidul Islam;Mst. Sayedatun Nessa Sumaia;Zeaur Rahim;Kamrul Islam;Asif Iqbal
    • Genomics & Informatics
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    • v.21 no.3
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    • pp.42.1-42.23
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    • 2023
  • Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

Heterosis Effects on Jumping Height and Body Weight in Three-Way Rotational Crossing in Mice

  • Kurnianto, E.;Shinjo, A.;Suga, D.;Nakada, T.;Sunagawa, K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.13 no.10
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    • pp.1353-1358
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    • 2000
  • The three-way rotational crossing experiment has been conducted to evaluate heterosis effects on jumping height and body weight. Yonakuni wild mice (Y) and two genetic groups of $CF_{{\sharp}1}$ (C) and C3H/HeNCrj (H) laboratory mice were used as materials. Reciprocal rotational crossing was made by crossing C male${\times}$Y female and Y male${\times}$C female to produce basic group designated $G_0$ and ${G_0}^{\prime}$, respectively. The females of the $G_0$ and ${G_0}^{\prime}$ were mated to the H sire to produce second generation ($G_1$ and ${G_1}^{\prime}$), and at the following generation the replacement females were mated to Y or C sire according to the basic group to produce $G_2$ to $G_3$ and ${G_2}^{\prime}$ to ${G_3}^{\prime}$. Individual jumping height data at Wk6 and body weight data at 1 (Wk1), 3 (Wk3), 6 (Wk6) and 10 (Wk10) weeks of age were analyzed. The results showed that effects of genetic group, sex and interaction of genetic group by sex were significant (p<0.01) for jumping height. For males, 55.34%~79.17% and 54.46%~78.29% of heterosis were reached at $G_1$ to $G_3$ and ${G_1}^{\prime}$ to ${G_3}^{\prime}$, respectively. While for females at $G_1$ to $G_3$ and at ${G_1}^{\prime}$ to ${G_3}^{\prime}$, heterosis effects were 61.53%~80.42% and 47.79%~85.86%, respectively. For body weight, genetic group was a significant source of variation at all ages studied. Sex effect was significant at Wk3, Wk6 and Wk10, and interaction between genetic group and sex was significant at Wk6 and Wk10 (p<0.01). C sires resulted in the highest body weight of offspring, while H sires were the intermediate and Y sires were the lightest. The significant positive and negative heterosis effects for body weight were exhibited. Crossing involved the Y sires in addition to smaller maternal effects of Y dams tended to result in small heterosis.

A Study of Some Economic Traits of Indigenous Cattle and their Crossbreeds in Southern Bangladesh

  • Ashraf, A.;Islam, S.S.;Islam, A.B.M.M.;Ali, S.Z.
    • Asian-Australasian Journal of Animal Sciences
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    • v.13 no.9
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    • pp.1189-1192
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    • 2000
  • The experiment was conducted on 69 cows to identify the quantitative variations of some economic traits of five genetic groups as $Local{\times}Friesian $ $F_1$, $Local{\times}Sahiwal$ $F_1$, Local (indigenous zebu type), $Local{\times}Sindhi $ $F_1$, and $Local{\times}Hariana$ $F_1$. The traits studied were age at weaning, age at first heat, age at first conception, services per conception, daily milk yield, lactation length, lactation yield and post partum heat period. The records on milking and reproduction performances of cows and heifers were obtained from farm register and by interviewing the farmers. It was observed that the lowest age at weaning, age at first heat and age at first conception were $5.37{\pm}0.24$, $27.17{\pm}1.72$ and $27.83{\pm}1.82$ months respectively in $Local{\times}Hariana$ $F_1$. Services per conception were lowest in $Local{\times}Sahiwal$ $F_1$ $(1.08{\pm}0.18)$ although not significantly (p>0.05) affected by farms, genetic groups and $farm{\times}genetic$ groups interaction. Average daily milk yield was highest in $Local{\times}Friesian$ $F_1$ $(5.81 {\pm}0.40 kg)$. Lactation length and lactation yield were highest in $Local{\times}Sahiwal$ $F_1$ ($299.38{\times}9.74$ days and $1863.00{\pm}141.00kg $ respectively). Average post partum heat period was lowest in $Local{\times}Sindhi$ $F_1$ ($3.19{\pm}0.38$ months). Least squares ANOVA showed that farm had significant (p<0.001) effect on age at weaning, age at first heat, age at first conception and post partum heat period. There was insignificant (p>0.05) effect of farm on services per conception, daily milk yield, lactation length and lactation yield, whereas genetic groups had a significant effect for all the traits under review except services per conception. $Farm{\times}genetic$ groups interaction was insignificant for all of the traits under consideration except age at weaning.

Biochemical Analysis of Interaction between Kringle Domains of Plasminogen and Prion Proteins with Q167R Mutation

  • Lee, Jeongmin;Lee, Byoung Woo;Kang, Hae-Eun;Choe, Kevine K.;Kwon, Moosik;Ryou, Chongsuk
    • Journal of Microbiology and Biotechnology
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    • v.27 no.5
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    • pp.1023-1031
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    • 2017
  • The conformational change of cellular prion protein ($PrP^C$) to its misfolded counterpart, termed $PrP^{Sc}$, is mediated by a hypothesized cellular cofactor. This cofactor is believed to interact directly with certain amino acid residues of $PrP^C$. When these are mutated into cationic amino acid residues, $PrP^{Sc}$ formation and prion replication halt in a dominant negative (DN) manner, presumably due to strong binding of the cofactor to mutated $PrP^C$, designated as DN PrP mutants. Previous studies demonstrated that plasminogen and its kringle domains bind to PrP and accelerate $PrP^{Sc}$ generation. In this study, in vitro binding analysis of kringle domains of plasminogen to Q167R DN mutant PrP (PrPQ167R) was performed in parallel with the wild type (WT) and Q218K DN mutant PrP (PrPQ218K). The binding affinity of PrPQ167R was higher than that of WT PrP, but lower than that of PrPQ218K. Scatchard analysis further indicated that, like PrPQ218K and WT PrP, PrPQ167R interaction with plasminogen occurred at multiple sites, suggesting cooperativity in this interaction. Competitive binding analysis using $\small{L}$-lysine or $\small{L}$-arginine confirmed the increase of the specificity and binding affinity of the interaction as PrP acquired DN mutations. Circular dichroism spectroscopy demonstrated that the recombinant PrPs used in this study retained the ${\alpha}$-helix-rich structure. The ${\alpha}$-helix unfolding study revealed similar conformational stability for WT and DN-mutated PrPs. This study provides an additional piece of biochemical evidence concerning the interaction of plasminogen with DN mutant PrPs.

hOGG1, p53 Genes, and Smoking Interactions are Associated with the Development of Lung Cancer

  • Cheng, Zhe;Wang, Wei;Song, Yong-Na;Kang, Yan;Xia, Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1803-1808
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    • 2012
  • This study aimed to investigate the effects of Ser/Cys polymorphism in hOGG1 gene, Arg/Pro polymorphism in p53 gene, smoking and their interactions on the development of lung cancer. Ser/Cys polymorphism in hOGG1 and Arg/Pro polymorphism in p53 among 124 patients with lung cancer and 128 normal people were detected using PCR-RFLP. At the same time, smoking status was investigated between the two groups. Logistic regression was used to estimate the effects of Ser/Cys polymorphism and Arg/Pro polymorphisms, smoking and their interactions on the development of lung cancer. ORs (95% CI) of smoking, hOGG1 Cys/Cys and p53 Pro/Pro genotypes were 2.34 (1.41-3.88), 2.12 (1.03-4.39), and 2.12 (1.15-3.94), respectively. The interaction model of smoking and Cys/Cys was super-multiplicative or multiplicative, and the OR (95% CI) for their interaction item was 1.67 (0.36 -7.78). The interaction model of smoking and Pro/Pro was super-multiplicative with an OR (95%CI) of their interaction item of 5.03 (1.26-20.1). The interaction model of Pro/Pro and Cys/Cys was multiplicative and the OR (95%CI) of their interaction item was 0.99 (0.19-5.28). Smoking, hOGG1 Cys/Cys, p53 Pro/Pro and their interactions may be the important factors leading to the development of lung cancer.

A Study on Interaction Modes among Populations in Cooperative Coevolutionary Algorithm for Supply Chain Network Design (공급사슬 네트워크 설계를 위한 협력적 공진화 알고리즘에서 집단들간 상호작용방식에 관한 연구)

  • Han, Yongho
    • Korean Management Science Review
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    • v.31 no.3
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    • pp.113-130
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    • 2014
  • Cooperative coevolutionary algorithm (CCEA) has proven to be a very powerful means of solving optimization problems through problem decomposition. CCEA implies the use of several populations, each population having the aim of finding a partial solution for a component of the considered problem. Populations evolve separately and they interact only when individuals are evaluated. Interactions are made to obtain complete solutions by combining partial solutions, or collaborators, from each of the populations. In this respect, we can think of various interaction modes. The goal of this research is to develop a CCEA for a supply chain network design (SCND) problem and identify which interaction mode gives the best performance for this problem. We present general design principle of CCEA for the SCND problem, which require several co-evolving populations. We classify these populations into two groups and classify the collaborator selection scheme into two types, the random-based one and the best fitness-based one. By combining both two groups of population and two types of collaborator selection schemes, we consider four possible interaction modes. We also consider two modes of updating populations, the sequential mode and the parallel mode. Therefore, by combining both four possible interaction modes and two modes of updating populations, we investigate seven possible solution algorithms. Experiments for each of these solution algorithms are conducted on a few test problems. The results show that the mode of the best fitness-based collaborator applied to both groups of populations combined with the sequential update mode outperforms the other modes for all the test problems.

Prediction of RNA structures containing pseudoknots

  • Lee, Dong-Kyu;Han, Kyung-Sook
    • Bioinformatics and Biosystems
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    • v.1 no.1
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    • pp.73-81
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    • 2006
  • This paper describes a genetic algorithm for predicting RNA structures that contain various types of pseudoknots. Pseudoknotted RNA structures are much more difficult to predict by computational methods than RNA secondary structures, as they are more complex and the analysis is time-consuming. We developed an efficient genetic algorithm to predict RNA folding structures containing any type of pseudoknot, as well as a novel initial population method to decrease computational complexity and increase the accuracy of the results. We also used an interaction filter to decrease the size of the possible stem lists for long RNA sequences. We predicted RNA structures using a number of different termination conditions and compared the validity of the results and the times required for the analyses. The algorithm proved able to predict efficiently RNA structures containing various types of pseudoknots.

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Current Status of Genomic Epidemiology Reseach (유전체 역학연구의 동향)

  • Lee, Kyoung-Mu;Kang, Dae-Hee
    • Journal of Preventive Medicine and Public Health
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    • v.36 no.3
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    • pp.213-222
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    • 2003
  • Genomic epidemiology is defined as 'an evoking field of inquiring that uses the systematic application of epidemiologic methods are approaches in population-based studies of the impact of human genetic variation on health and disease (Khoury, 1998)'. Most human diseases are caused by the intricate interaction among environmental exposures and genetic susceptibility factors. Susceptibility genes involved in disease pathogenesis are categorized into two groups: high penetrance genes (i.e., BRAC1, RB, etc.) and lour penetranoe genes (i.e., GSTs, Cyps, XRCC1, ets.), and low penetrance susceptibility genes has the higher priority for epidemiological research due to high population attributable risk. In this paper, the summarized results of the association study between single nucleotide polymorphisms (SNPs) and breast cancer in Korea were introduced and the international trends of genomic epidemiology research were reviewed with an emphasis on internee-based case-control and cohort consortium.