• Title/Summary/Keyword: Genetic interaction

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Estimation of Interaction Effects among Nucleotide Sequence Variants in Animal Genomes

  • Lee, Chaeyoung;Kim, Younyoung
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.1
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    • pp.124-130
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    • 2009
  • Estimating genetic interaction effects in animal genomics would be one of the most challenging studies because the phenotypic variation for economically important traits might be largely explained by interaction effects among multiple nucleotide sequence variants under various environmental exposures. Genetic improvement of economic animals would be expected by understanding multi-locus genetic interaction effects associated with economic traits. Most analyses in animal breeding and genetics, however, have excluded the possibility of genetic interaction effects in their analytical models. This review discusses a historical estimation of the genetic interaction and difficulties in analyzing the interaction effects. Furthermore, two recently developed methods for assessing genetic interactions are introduced to animal genomics. One is the restricted partition method, as a nonparametric grouping-based approach, that iteratively utilizes grouping of genotypes with the smallest difference into a new group, and the other is the Bayesian method that draws inferences about the genetic interaction effects based on their marginal posterior distributions and attains the marginalization of the joint posterior distribution through Gibbs sampling as a Markov chain Monte Carlo. Further developing appropriate and efficient methods for assessing genetic interactions would be urgent to achieve accurate understanding of genetic architecture for complex traits of economic animals.

Human-yeast genetic interaction for disease network: systematic discovery of multiple drug targets

  • Suk, Kyoungho
    • BMB Reports
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    • v.50 no.11
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    • pp.535-536
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    • 2017
  • A novel approach has been used to identify functional interactions relevant to human disease. Using high-throughput human-yeast genetic interaction screens, a first draft of disease interactome was obtained. This was achieved by first searching for candidate human disease genes that confer toxicity in yeast, and second, identifying modulators of toxicity. This study found potentially disease-relevant interactions by analyzing the network of functional interactions and focusing on genes implicated in amyotrophic lateral sclerosis (ALS), for example. In the subsequent proof-of-concept study focused on ALS, similar functional relationships between a specific kinase and ALS-associated genes were observed in mammalian cells and zebrafish, supporting findings in human-yeast genetic interaction screens. Results of combined analyses highlighted MAP2K5 kinase as a potential therapeutic target in ALS.

Detecting Genetic Association and Gene-Gene Interaction using Network Analysis in Case-Control Study

  • Jin, Seo-Hoon;Lee, Min-Hee;Lee, Hyo-Jung;Park, Mi-Ra
    • The Korean Journal of Applied Statistics
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    • v.25 no.4
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    • pp.563-573
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    • 2012
  • Various methods of analysis have been proposed to understand the gene-disease relation and gene-gene interaction effect for a disease through comparison of genotype in case-control study. In this study, we proposed the method to detect a genetic association and gene-gene interaction through the use of a network graph and centrality measures that are used in social network analysis. The applicability of the proposed method was studied through an analysis of real genetic data.

TCP10L synergizes with MAD1 in transcriptional suppression and cell cycle arrest through mutual interaction

  • Shen, Suqin;Zuo, Jie;Feng, Huan;Bai, Meirong;Wang, Chenji;Wei, Youheng;Li, Yanhong;Le, Yichen;Wu, Jiaxue;Wu, Yanhua;Yu, Long
    • BMB Reports
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    • v.49 no.6
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    • pp.325-330
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    • 2016
  • T-complex protein 10A homolog 2 (TCP10L) was previously demonstrated to be a potential tumor suppressor in human hepatocellular carcinoma (HCC). However, little is known about the molecular mechanism. MAX dimerization protein 1 (MAD1) is a key transcription suppressor that is involved in regulating cell cycle progression and Myc-mediated cell transformation. In this study, we identified MAD1 as a novel TCP10L-interacting protein. The interaction depends on the leucine zipper domain of both TCP10L and MAD1. TCP10L, but not the interaction-deficient TCP10L mutant, synergizes with MAD1 in transcriptional repression, cell cycle G1 arrest and cell growth suppression. Mechanistic exploration further revealed that TCP10L is able to stabilize intracellular MAD1 protein level. Consistently, the MAD1-interaction-deficient TCP10L mutant exerts no effect on stabilizing the MAD1 protein. Taken together, our results strongly indicate that TCP10L stabilizes MAD1 protein level through direct interaction, and they cooperatively regulate cell cycle progression.

Influence of Inbreeding Depression on Genetic (Co)Variance and Sire-by-Year Interaction Variance Estimates for Weaning Weight Direct-Maternal Genetic Evaluation

  • Lee, C.;Pollak, E.J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.10 no.5
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    • pp.510-513
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    • 1997
  • This study examined the effects of ignoring inbreeding depression on (co)variance components for weaning weight through the use of Monte Carlo simulation. Weaning weight is of particular interest as a trait for which additive direct and maternal genetic components exist and there then is the potential for a direct-maternal genetic covariance. Ignoring inbreeding depression in the analytical model (.8 kg reduction of phenotypic value per 1% inbreeding) led to biased estimates of all genetic (co) variance components, all estimates being larger than the true values of the parameters. In particular, a negative bias in the direct-maternal genetic covariance was observed in analyses that ignored inbreeding depression. A small spurious sire-by-year interaction variance was also observed.

Heritability and Genetic Gains for Height Growth in 20-year-Old Korean White Pine in Korea

  • Shin, Man-Yong;Park, Hyung-Soon;Cho, Yoon-Jin;Chung, Dong-Jun
    • Korean Journal of Plant Resources
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    • v.19 no.6
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    • pp.677-679
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    • 2006
  • The objectives of this study were to examine the genetic variation of 20-year-old tree height and to estimate heritabilities and genetic gains of Korean white pine. Analysis of variance showed that families and family x block interaction had the significant (p=0.01) effects on tree height. However, family variation appears to be much greater than the variation due to family x block interaction. Individual tree heritability was higher ($h_I^2=0.73$) than family heritability, ($h_F^2=0.83$) therefore, combined selection showed the largest genetic gain (17.76%) in a given equal intensity of selection.

SEPT12 Interacts with SEPT6 and This Interaction Alters the Filament Structure of SEPT6 in Hela Cells

  • Ding, Xiangming;Yu, Wenbo;Liu, Ming;Shen, Suqin;Chen, Fang;Wan, Bo;Yu, Long
    • BMB Reports
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    • v.40 no.6
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    • pp.973-978
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    • 2007
  • Septins are a family of conserved cytoskeletal GTPase forming heteropolymeric filamentous structure in interphase cells, however, the mechanism of assembly are largely unknown. Here we described the characterization of SEPT12, sharing closest homology to SEPT3 and SEPT9. It was revealed that subcelluar localization of SEPT12 varied at interphase and mitotic phase. While SEPT12 formed filamentous structures at interphase, it was localized to the central spindle and to midbody during anaphase and cytokinesis, respectively. In addition, we found that SEPT12 can interact with SEPT6 in vitro and in vivo, and this interaction was independent of the coiled coil domain of SEPT6. Further, co-expression of SEPT12 altered the filamentous structure of SEPT6 in Hela cells. Therefore, our result showed that the interaction between different septins may affect the septin filament structure.

On the Negative Estimates of Direct and Maternal Genetic Correlation - A Review

  • Lee, C.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.8
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    • pp.1222-1226
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    • 2002
  • Estimates of genetic correlation between direct and maternal effects for weaning weight of beef cattle are often negative in field data. The biological existence of this genetic antagonism has been the point at issue. Some researchers perceived such negative estimate to be an artifact from poor modeling. Recent studies on sources affecting the genetic correlation estimates are reviewed in this article. They focus on heterogeneity of the correlation by sex, selection bias caused from selective reporting, selection bias caused from splitting data by sex, sire by year interaction variance, and sire misidentification and inbreeding depression as factors contributing sire by year interaction variance. A biological justification of the genetic antagonism is also discussed. It is proposed to include the direct-maternal genetic covariance in the analytical models.

The Genetic Development of Sire, Dam and Progenies and Genotype ${\times}$ Environment Interaction in a Beef Breeding System

  • Bhuiyan, A.K.F.H.;Dietl, G.;Klautschek, G.
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.1
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    • pp.13-17
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    • 2004
  • The aim of this study was to investigate genetic development and genotype${\times}$environment interactions (GEI) in postweaning body weight of fattening bulls at the end of test period (WT-T) under various beef fattening environments. Data on a total of 24,247 fattening bulls obtained from the industrial farm, breeding farms and testing stations were used. Heritability estimates for WT-T in all environments were nearly similar. Significant genetic developments of sire, dam and progenies for WT-T were observed in all environments. However, many differences in annual genetic developments between the environments were significant. The genetic correlations for WT-T between industrial farm and breeding farms, industrial farm and testing stations and breeding farms and testing stations were respectively 0.004, 0.004 and 0.013. These low estimates of genetic correlations and significant differences in genetic developments among environments clearly show the existence of GEI for WT-T among various fattening environments. Results of this study indicate the need for environment-specific genetic evaluation and selection of beef bulls for commercial beef production.

Suicide : Gene-Environment Interaction (자살 : 유전자-환경 상호작용)

  • Kim, Yong-Ku
    • Korean Journal of Biological Psychiatry
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    • v.17 no.2
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    • pp.65-69
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    • 2010
  • Gene-environment interactions are important in pathogenesis of suicide or suicidal behavior. Twin and adoption studies and family studies show that genetic factors play a critical role in suicide or suicidal behavior. Given the strong association between serotonergic neurotransmission and suicide, recent molecular genetic studies have focused on polymorphisms of serotonin genes, especially on serotonin transporter and tryptophan hydroxylase genes. Some studies have revealed a significant interaction between s allele of the serotonin transporter gene and the risk of suicide attempt associated with childhood trauma. In addition, the polymorphism of brain-derived neurotrophic factor gene also may influence the effect of childhood trauma in relation to the risk of attempting suicide. Future studies should explore genetic and environmental factors in suicide or suicidal behavior and examine for gene and environment interaction.