Project description:These studies adress differential changes in gene expression between 6h sleep deprived and control mice in the brain and the liver. We profiled gene expression in three different inbred strains to understand the influence of genetic background. Keywords: brain, genetic background, sleep deprivation
Project description:These studies adress differential changes in gene expression between sleep deprived and control mice. We profiled gene expression at four time points across the 24H Light/Dark cycle to take into account circadian influences and used three different inbred strains to understand the influence of genetic background. Keywords: brain, circadian, genetic background, sleep deprivation
Project description:Previous studies have documented the diversity of genetic background of methicillin-resistant S. aureus (MRSA) strains associated with healthcare (HA-MRSA), community (CA-MRSA) and livestock (LA-MRSA). The accessory and core-variable genome content of those strains remain largely unknown. To compare the composition of accessory and core-variable genome of Belgian MRSA strains according to host, population setting and genetic background, representative strains of HA- (n=21), CA- (n = 13) and ST398 LA-MRSA (n = 18) were characterized by a DNA-microarray (StaphVar Array) composed of oligonucleotide probes targeting ~400 resistance, adhesion and virulence associated genes.ST398 strains displayed very homogenous hybridization profiles (>94% gene content homology) irrespective of their host origin. This “ST398-specific” genomic profile was not distantly demarked from those of certain human-associated lineages but lacked several virulence- and colonization-associated genes harbored by strains of human origin, such as genes encoding proteases, haemolysins or adhesins. No enterotoxin gene was found among ST398 strains. In conclusion, our findings are consistent with a non-human origin of this ST398 lineage but suggest that it might have the potential to adapt further to the human host.
Project description:Genetic background effects contribute to the phenotypic consequences of mutations, and are pervasive across all domains of life that have been examined, yet little is known about how they modify genetic systems. In part this is due to the lack of tractable model systems that have been explicitly developed to study the genetic and evolutionary consequences of background effects. In this study we demonstrate that phenotypic expressivity of the scalloped[E3] mutation of Drosophila melanogaster is background dependent, and is the result of at least one major modifier segregating between two standard lab wild-type strains. Microarrays were used to examine the consequences of genetic background effects on the global transcriptome. Expression differences between wild-type strains were found to be as large or larger than the effects of mutations with substantial phenotypic effects, and expression differences between wild-type and mutant varied significantly between genetic backgrounds. Significantly, we demonstrate that the epistatic interaction between sd[E3] and an optomotor blind mutation is background dependent. The results are discussed within the context of developing a complex but more realistic view of the consequences of genetic background effects with respect to mutational analysis, and studies of epistasis and cryptic genetic variation segregating in natural populations Keywords: Mutant vs wild-type comparison
Project description:The immune system illustrates the challenges of assigning risk to low dose radiation (LDR) exposure in a population. While high radiation doses clearly suppress immune function, a number of studies have shown that LDR affects immune cell subpopulations in ways that could be beneficial. In the intact organism, defining the consequences of LDR is further complicated by the impact of genetic background, particularly in systems such as the immune system for which both radiosensitivity and genetic effects are profound. We employed a systems genetics approach to test for heritable differences in LDR responses. Mice from 39 BXD recombinant inbred (RI) strains were exposed to 10cGy gamma radiation to determine effects on immune function and oxidative stress 48h after irradiation. LDR significantly enhanced neutrophil phagocytosis in a manner that was independent of genetic background. In contrast, genetic background significantly impacted LDR-induced changes in spleen superoxide dismutase activity. Transcriptome data from spleens of the BXD parental strains highlighted the impact of genetic background on LDR responses and also indicate that genetic variation in radiosensitivity is further unmasked at low radiation doses. Taken together, these data highlight the need to consider genetic variation when assessing LDR outcomes.
Project description:Trichloroethylene (TCE) is a widely used industrial chemical, and a common environmental contaminant. It is a well-known carcinogen in rodents and a probable carcinogen in humans. Studies utilizing panels of mouse inbred strains afford a unique opportunity to understand both metabolic and genetic basis for differences in responses to TCE. We tested the hypothesis that individual and liver-specific toxic effects of TCE are genetically controlled and that the mechanisms of toxicity and susceptibility can be uncovered by exploring responses to TCE using a diverse panel of inbred mouse strains. TCE (2100 mg/kg) or corn oil vehicle were administered by gavage to 6-8 wk old male mice of 15 mouse strains. Serum and liver were collected at 2, 8, and 24 hr post dosing and were analyzed for TCE metabolites, hepatocellular injury and gene expression of liver. TCE metabolism, as evident from the levels of individual oxidative and conjugative metabolites, varied considerably between strains. TCE treatment-specific effect on the liver transcriptome was strongly dependent on the individual’s genetic background. PPAR-mediated molecular networks, consisting of the metabolism genes known to be induced by TCE, represent some of the most pronounced molecular effects of TCE treatment in mouse liver that are dependent on the individual’s genetic background. Conversely, cell death, liver necrosis, and immune mediated response pathways which are affected by TCE treatment in liver are largely genetic background-independent. These studies provide better understanding of the mechanisms of TCE-induced toxicity anchored on metabolism and genotype-phenotype correlations that may define susceptibility or resistance.
Project description:Genetic background effects contribute to the phenotypic consequences of mutations, and are pervasive across all domains of life that have been examined, yet little is known about how they modify genetic systems. In part this is due to the lack of tractable model systems that have been explicitly developed to study the genetic and evolutionary consequences of background effects. In this study we demonstrate that phenotypic expressivity of the scalloped[E3] mutation of Drosophila melanogaster is background dependent, and is the result of at least one major modifier segregating between two standard lab wild-type strains. Microarrays were used to examine the consequences of genetic background effects on the global transcriptome. Expression differences between wild-type strains were found to be as large or larger than the effects of mutations with substantial phenotypic effects, and expression differences between wild-type and mutant varied significantly between genetic backgrounds. Significantly, we demonstrate that the epistatic interaction between sd[E3] and an optomotor blind mutation is background dependent. The results are discussed within the context of developing a complex but more realistic view of the consequences of genetic background effects with respect to mutational analysis, and studies of epistasis and cryptic genetic variation segregating in natural populations Keywords: Mutant vs wild-type comparison 2 wild-type strains of D. melanogaster (Oregon-R and Samarkand, both marked with white) each with and without the scalloped[E3] mutation. Thus a 2x2 factorial design with a balanced incomplete block (block=slide) design in a full loop configuration with dye swapping.
Project description:Five different mitochondrial strains were introgressed in male and female fruit flies with identical (w1118) nuclear genetic background.
Project description:Trichloroethylene (TCE) is a widely used industrial chemical, and a common environmental contaminant. It is a well-known carcinogen in rodents and a probable carcinogen in humans. Studies utilizing panels of mouse inbred strains afford a unique opportunity to understand both metabolic and genetic basis for differences in responses to TCE. We tested the hypothesis that individual and liver-specific toxic effects of TCE are genetically controlled and that the mechanisms of toxicity and susceptibility can be uncovered by exploring responses to TCE using a diverse panel of inbred mouse strains. TCE (2100 mg/kg) or corn oil vehicle were administered by gavage to 6-8 wk old male mice of 15 mouse strains. Serum and liver were collected at 2, 8, and 24 hr post dosing and were analyzed for TCE metabolites, hepatocellular injury and gene expression of liver. TCE metabolism, as evident from the levels of individual oxidative and conjugative metabolites, varied considerably between strains. TCE treatment-specific effect on the liver transcriptome was strongly dependent on the individual’s genetic background. PPAR-mediated molecular networks, consisting of the metabolism genes known to be induced by TCE, represent some of the most pronounced molecular effects of TCE treatment in mouse liver that are dependent on the individual’s genetic background. Conversely, cell death, liver necrosis, and immune mediated response pathways which are affected by TCE treatment in liver are largely genetic background-independent. These studies provide better understanding of the mechanisms of TCE-induced toxicity anchored on metabolism and genotype-phenotype correlations that may define susceptibility or resistance. 16 mouse strains were studied, vehicle control and mice treated by gavage with 2100 mg/kg Trichloroethylene and sacrificed 24 hrs after dosing
Project description:Recombinant inbred lines were created by crossing the alpha-synuclein containing Caenorhabditis elegans strains NL5901 and SCH4856. These strains contain the human alpha-synuclein gene fused to YFP and under the control of an unc-54 promotor (unc-54p::alpha-synnuclein::YFP) in an N2 and CB4856 genetic background, respectively. These two strains were used to generate a total of 212 recombinant inbred lines, of which 88 were genotyped by whole-genome sequencing using a MiSeq. These recombinant inbred lines can be used for mapping genetic modifiers affecting protein accumulation.