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Kenji Sakimura - One of the best experts on this subject based on the ideXlab platform.

  • conditional gene targeting on the pure c57bl 6 Genetic Background
    Neuroscience Research, 2007
    Co-Authors: Masayoshi Mishina, Kenji Sakimura
    Abstract:

    Brain functions are the products of dynamic interactions between multiple genes and environments. Accordingly, there are large differences among mouse strains at the behavioral and neurobiological levels. Therefore, it is crucial to manipulate genes on the same and homogenous Genetic Background and then to analyze and compare the phenotypes of various Genetically modified mice. Furthermore, a conditional gene targeting to restrict the gene knockout to specific cells and time is a powerful tool to investigate the molecular basis of higher brain functions such as learning and memory. We have developed a system employing Cre-progesterone receptor fusion recombinase for temporal regulation of gene targeting and Flp/frt recombination system for elimination of marker genes. Importantly, both the recombinase lines and target mice have been produced with embryonic stem cells derived from the C57BL/6 strain suitable for brain function analysis. Thus, we have established an inducible and neuron-specific gene targeting system on the pure C57BL/6 Genetic Background.

  • Conditional gene targeting on the pure C57BL/6 Genetic Background.
    Neuroscience research, 2007
    Co-Authors: Masayoshi Mishina, Kenji Sakimura
    Abstract:

    Brain functions are the products of dynamic interactions between multiple genes and environments. Accordingly, there are large differences among mouse strains at the behavioral and neurobiological levels. Therefore, it is crucial to manipulate genes on the same and homogenous Genetic Background and then to analyze and compare the phenotypes of various Genetically modified mice. Furthermore, a conditional gene targeting to restrict the gene knockout to specific cells and time is a powerful tool to investigate the molecular basis of higher brain functions such as learning and memory. We have developed a system employing Cre-progesterone receptor fusion recombinase for temporal regulation of gene targeting and Flp/frt recombination system for elimination of marker genes. Importantly, both the recombinase lines and target mice have been produced with embryonic stem cells derived from the C57BL/6 strain suitable for brain function analysis. Thus, we have established an inducible and neuron-specific gene targeting system on the pure C57BL/6 Genetic Background.

Masayoshi Mishina - One of the best experts on this subject based on the ideXlab platform.

  • conditional gene targeting on the pure c57bl 6 Genetic Background
    Neuroscience Research, 2007
    Co-Authors: Masayoshi Mishina, Kenji Sakimura
    Abstract:

    Brain functions are the products of dynamic interactions between multiple genes and environments. Accordingly, there are large differences among mouse strains at the behavioral and neurobiological levels. Therefore, it is crucial to manipulate genes on the same and homogenous Genetic Background and then to analyze and compare the phenotypes of various Genetically modified mice. Furthermore, a conditional gene targeting to restrict the gene knockout to specific cells and time is a powerful tool to investigate the molecular basis of higher brain functions such as learning and memory. We have developed a system employing Cre-progesterone receptor fusion recombinase for temporal regulation of gene targeting and Flp/frt recombination system for elimination of marker genes. Importantly, both the recombinase lines and target mice have been produced with embryonic stem cells derived from the C57BL/6 strain suitable for brain function analysis. Thus, we have established an inducible and neuron-specific gene targeting system on the pure C57BL/6 Genetic Background.

  • Conditional gene targeting on the pure C57BL/6 Genetic Background.
    Neuroscience research, 2007
    Co-Authors: Masayoshi Mishina, Kenji Sakimura
    Abstract:

    Brain functions are the products of dynamic interactions between multiple genes and environments. Accordingly, there are large differences among mouse strains at the behavioral and neurobiological levels. Therefore, it is crucial to manipulate genes on the same and homogenous Genetic Background and then to analyze and compare the phenotypes of various Genetically modified mice. Furthermore, a conditional gene targeting to restrict the gene knockout to specific cells and time is a powerful tool to investigate the molecular basis of higher brain functions such as learning and memory. We have developed a system employing Cre-progesterone receptor fusion recombinase for temporal regulation of gene targeting and Flp/frt recombination system for elimination of marker genes. Importantly, both the recombinase lines and target mice have been produced with embryonic stem cells derived from the C57BL/6 strain suitable for brain function analysis. Thus, we have established an inducible and neuron-specific gene targeting system on the pure C57BL/6 Genetic Background.

Benoît Moury - One of the best experts on this subject based on the ideXlab platform.

  • Role of the Genetic Background in Resistance to Plant Viruses.
    International journal of molecular sciences, 2018
    Co-Authors: Jean-luc Gallois, Benoît Moury, Sylvie German-retana
    Abstract:

    In view of major economic problems caused by viruses, the development of Genetically resistant crops is critical for breeders but remains limited by the evolution of resistance-breaking virus mutants. During the plant breeding process, the introgression of traits from Crop Wild Relatives results in a dramatic change of the Genetic Background that can alter the resistance efficiency or durability. Here, we conducted a meta-analysis on 19 Quantitative Trait Locus (QTL) studies of resistance to viruses in plants. Frequent epistatic effects between resistance genes indicate that a large part of the resistance phenotype, conferred by a given QTL, depends on the Genetic Background. We next reviewed the different resistance mechanisms in plants to survey at which stage the Genetic Background could impact resistance or durability. We propose that the Genetic Background may impair effector-triggered dominant resistances at several stages by tinkering the NB-LRR (Nucleotide Binding-Leucine-Rich Repeats) response pathway. In contrast, effects on recessive resistances by loss-of-susceptibility—such as eIF4E-based resistances—are more likely to rely on gene redundancy among the multigene family of host susceptibility factors. Finally, we show how the Genetic Background is likely to shape the evolution of resistance-breaking isolates and propose how to take this into account in order to breed plants with increased resistance durability to viruses.

  • Farther, slower, stronger: how the plant Genetic Background protects a major resistance gene from breakdown
    Molecular Plant Pathology, 2013
    Co-Authors: Julie Quenouille, Josselin Montarry, Alain Palloix, Benoît Moury
    Abstract:

    Genetic resistance provides efficient control of crop diseases, but is limited by pathogen evolution capacities which often result in resistance breakdown. It has been demonstrated recently, in three different pathosystems, that polygenic resistances combining a major-effect gene and quantitative resistance controlled by the Genetic Background are more durable than monogenic resistances (with the same major gene in a susceptible Genetic Background), but the underlying mechanisms are unknown. Using the pepper–Potato virus Y system, we examined three mechanisms that could account for the greater durability of the polygenic resistances: (i) the additional quantitative resistance conferred by the Genetic Background; (ii) the increase in the number of mutations required for resistance breakdown; and (iii) the slower selection of adapted resistance-breaking mutants within the viral population. The three mechanisms were experimentally validated. The first explained a large part of the variation in resistance breakdown frequency and is therefore expected to be a major determinant of resistance durability. Quantitative resistance factors also had an influence on the second mechanism by modifying the virus mutational pathways towards resistance breakdown and could also have an influence on the third mechanism by increasing Genetic drift effects on the viral population. The relevance of these results for other plant–pathogen systems and their importance in plant breeding are discussed.

Anke Van Dijck - One of the best experts on this subject based on the ideXlab platform.

Lucilla Pizzo - One of the best experts on this subject based on the ideXlab platform.

  • Rare variants in the Genetic Background modulate cognitive and developmental phenotypes in individuals carrying disease-associated variants
    Genetics in Medicine, 2019
    Co-Authors: Lucilla Pizzo, Matthew Jensen, Andrew Polyak, Katrin Mannik, Arjun Krishnan, Elizabeth Mccready, Olivier Pichon, Jill Rosenfeld, Cédric Le Caignec, Anke Van Dijck
    Abstract:

    To assess the contribution of rare variants in the Genetic Background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants.

  • rare variants in the Genetic Background modulate the expressivity of neurodevelopmental disorders
    bioRxiv, 2018
    Co-Authors: Lucilla Pizzo, Matthew Jensen, Andrew Polyak, Jill A Rosenfeld, Katrin Mannik, Arjun Krishnan, Elizabeth Mccready, Olivier Pichon, Cedric Le Caignec
    Abstract:

    Rare copy-number variants (CNVs) and gene-disruptive mutations associated with neurodevelopmental disease are characterized by phenotypic heterogeneity. When affected children inherit these mutations, they usually present more severe features than carrier parents, leading to challenges in diagnosis and management. To understand how the Genetic Background modulates phenotypes of these variants, we analyzed clinical and exome-sequencing data from 757 probands and 233 parents and siblings who carry disease-associated mutations. We found that the number of rare pathogenic secondary mutations in developmental genes (second-hits) modulates the expressivity of disease in probands with 16p12.1 deletion (n=26, p=0.014) and in autism probands with gene-disruptive mutations (n=184, p=0.031) when compared to their carrier family members. Probands with 16p12.1 deletion and a strong family history of neuropsychiatric disease were more likely to manifest multiple and more severe clinical features (p=0.035) and carry a higher burden of second-hits compared to those with mild or no family history (p=0.001). The amount of secondary variants determined the severity of cognitive impairment in 432 probands carrying pathogenic rare CNVs or de novo mutations in disease genes and negatively correlated with head size in 84 probands with 16p11.2 deletion, suggesting an effect of the Genetic Background across multiple phenotypic domains. These second-hits involved known disease genes, such as SETD5, AUTS2, and NRXN1, and novel candidate modifiers, such as CDH23, RYR3, and DNAH3, affecting core developmental processes. Our findings suggest that in the era of personalized medicine, accurate diagnosis will require complete evaluation of the Genetic Background even after a candidate gene mutation is identified.