Mouse transcriptome of two genetic mutations of Grm1
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE155252 | GEO | 2020/10/16
REPOSITORIES: GEO
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Project description:Mouse transcriptome of two genetic mutations of Grm1
| PRJNA649166 | ENA
Project description:Background: Methanol is present in most ecosystems and may also occur in industrial applications, e.g. as an impurity of carbon sources such as technical glycerol. Methanol often inhibits growth of bacteria, thus, methanol tolerance may limit fermentative production processes. Results: The methanol tolerance of the amino acid producing soil bacterium Corynebacterium glutamicum was improved by genetic adaption in the presence of methanol. The resulting strain Tol1 exhibited significantly increased growth rates in the presence of up to 1 M methanol. However, neither transcriptional changes nor increased enzyme activities of the linear methanol oxidation pathway were observed, which was in accordance with the finding that tolerance to the downstream metabolites formaldehyde and formate was not improved. Genome sequence analysis of strain Tol1 revealed two point mutations potentially relevant to enhanced methanol tolerance: one leading to the amino acid exchange A165T of O-acetylhomoserine sulfhydrolase MetY and the other leading to shortened CoA transferase Cat (Q342*). Introduction of either mutation into the genome of C. glutamicum wild type increased methanol tolerance and introduction of both mutations into C. glutamicum was sufficient to achieve methanol tolerance almost indistinguishable from that of strain Tol1. Conclusion: The methanol tolerance of C. glutamicum can be increased by two point mutations leading to amino acid exchange of O-acetylhomoserine sulfhydrolase MetY and shortened CoA transferase Cat. Introduction of these mutations into producer strains may be helpful when using carbon sources containing methanol as component or impurity.
2015-08-01 | GSE71590 | GEO
Project description:Background: Methanol is present in most ecosystems and may also occur in industrial applications, e.g. as an impurity of carbon sources such as technical glycerol. Methanol often inhibits growth of bacteria, thus, methanol tolerance may limit fermentative production processes. Results: The methanol tolerance of the amino acid producing soil bacterium Corynebacterium glutamicum was improved by genetic adaption in the presence of methanol. The resulting strain Tol1 exhibited significantly increased growth rates in the presence of up to 1 M methanol. However, neither transcriptional changes nor increased enzyme activities of the linear methanol oxidation pathway were observed, which was in accordance with the finding that tolerance to the downstream metabolites formaldehyde and formate was not improved. Genome sequence analysis of strain Tol1 revealed two point mutations potentially relevant to enhanced methanol tolerance: one leading to the amino acid exchange A165T of O-acetylhomoserine sulfhydrolase MetY and the other leading to shortened CoA transferase Cat (Q342*). Introduction of either mutation into the genome of C. glutamicum wild type increased methanol tolerance and introduction of both mutations into C. glutamicum was sufficient to achieve methanol tolerance almost indistinguishable from that of strain Tol1. Conclusion: The methanol tolerance of C. glutamicum can be increased by two point mutations leading to amino acid exchange of O-acetylhomoserine sulfhydrolase MetY and shortened CoA transferase Cat. Introduction of these mutations into producer strains may be helpful when using carbon sources containing methanol as component or impurity. The gene expression was analyzed in the methanol tolerant strain Tol1 in comparison to the C. glutamicumWT. Direct comparison in LB complex medium and analysis of expression response to methanol addition in mCGXII minimal medium with 100 mM glucose.
2015-08-01 | E-GEOD-71590 | biostudies-arrayexpress
Project description:Sleep is a conserved physiological process, and sleep loss typically imposes negative effects on animal health. However, natural short sleepers, who sleep less without the usual negative effects of sleep deprivation, exist in the human population. One example are individuals that possess rare genetic mutations in the human dec2 gene; these individuals sleep on average ~6hrs/day rather than the typical 8hrs/day. Like many natural short sleepers, humans harboring the dec2P384R mutation do not exhibit any obvious adverse phenotypes typically associated with sleep loss, suggesting that these individuals may require less total sleep/day to achieve the same physiological outcomes. Potentially, the dec2P384R mutation could activate compensatory mechanisms that allow these individuals to thrive with less sleep. To test this directly, we used a dec2P384R short sleep Drosophila model to understand the effects of the dec2P384R mutation on animal health and dissect the genetic mechanisms that might drive these physiological changes. We found that expression of the mammalian dec2P384R mutation in fly sleep neurons was sufficient to mimic the short sleep phenotype observed in mammals. Remarkably, dec2P384R lived significantly longer with improved health and memory despite having a short sleep phenotype. The improved physiological effects in dec2P384R mutants were enabled, in part, by enhanced mitochondrial fitness and upregulation of multiple stress response pathways. Moreover, we provide evidence that the improved health in dec2P384R mutants may also contribute to the short sleep phenotype, and this may extend to other pro-longevity mutants.
2023-04-26 | GSE230462 | GEO
Project description:Our objective was to determine whether gene expression in Drosophila melanogaster selectively bred for long or short night sleep duration changes detectably across generations. To meet this objective, we performed transcriptional profiling of ten pooled whole adult individuals from four selected populations and two control populations across 13 generations. We quantified differential expression among selection scheme (long sleep, short sleep, or unselected control), generation (generation 0; then generations 2-13), and sex for each gene.
2023-07-29 | GSE202600 | GEO
Project description:Purpose: Comorbid familial non-obstructive azoospermia (NOA) and congenital cataract (CC) has not been reported previously, and no single human gene has been associated with both diseases in humans. Our purpose is to uncover novel human mutations and genes causing familial NOA and CC. Methods: We performed whole-exome sequencing for two brothers with both NOA and CC from a consanguineous family.The proband was also carried out SNP array analysis. Mutation screening of TDRD7 was performed in another similar consanguineous family and 176 patients with azoospermia or CC alone and 520 healthy controls. Histological analysis was performed for the biopsied testicle sample in one patient, and knockout mice were constructed to verify the phenotype of the mutation in TDRD7. Results: Two novel loss-of-function mutations (c.324_325insA (T110Nfs*30) and (c.688-689insA (p.Y230X), respectively) of TDRD7 were found in the affected patients from the two unrelated consanguineous families. Histological analysis demonstrated a lack of mature sperm in the male patient’s seminiferous tubules. The mutations were not detected in patients with CC or NOA alone. Mice with Tdrd7 gene disrupted at a similar position precisely replicated the human syndrome. Conclusions: We identified TDRD7 causing CC as a new pathogenic gene for male azoospermia in human, with an autosomal recessive mode of inheritance.
2017-06-15 | GSE100019 | GEO
Project description:Short sleep duration is associated with adverse metabolic, cardiovascular, and inflammatory effects. Co-twin study methodologies account for familial (e.g., genetics and shared environmental) confounding, allowing assessment of subtle environmental effects, such as the effect of short habitual sleep duration on gene expression. Therefore, we sought to investigate gene expression in monozygotic twins discordant for actigraphically phenotyped habitual sleep duration. Eleven healthy monozygotic twin pairs (82% female; mean age 42.7 years; SD=18.1), selected based on subjective sleep duration discordance, were objectively phenotyped for habitual sleep duration with two-weeks of wrist actigraphy. Peripheral blood leukocyte (PBL) RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. Differential gene expression was determined between paired samples and mapped to functional categories using Gene Ontology. Next, a more comprehensive gene set enrichment analysis was performed based on the entire PBL transcriptome. The mean 24 hour sleep duration of the total sample was 439.2 minutes (SD=46.8 minutes; range 325.4 to 521.6 minutes). Mean within-pair sleep duration difference per 24 hours was 64.4 minutes (SD=21.2; range 45.9 to 114.6 minutes). The twin cohort displayed distinctive pathway enrichment based on sleep duration differences. Short sleep was associated with up-regulation of genes involved in transcription, ribosome, translation and oxidative phosphorylation. Unexpectedly, genes down-regulated in short sleep twins were highly enriched in immuno-inflammatory pathways such interleukin signaling and leukocyte activation, as well as developmental programs, coagulation cascade, and cell adhesion. Objectively assessed habitual sleep duration in monozygotic twin pairs appears to be associated with distinct patterns of differential gene expression and pathway enrichment. By accounting for familial confounding and measuring real life sleep duration, our study shows the transcriptomic effects of short sleep on dysregulated immune response and provides a potential link between sleep deprivation and adverse metabolic, cardiovascular and inflammatory outcomes.
2016-09-09 | GSE80612 | GEO
Project description:T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm with aggressive clinical course and short overall survival. So far, due to the rareness of this disease, genetic data is available only from individual cases or small cohorts. In our study, we aimed at performing a comprehensive cytogenetic and molecular genetic characterization of T-PLL comprising the largest cohort of patients with T-PLL analyzed so far, including correlations between the respective markers and their impact on prognosis. Genetic abnormalities were found in all 51 cases with T-PLL, most frequently involving the TCRA/D locus (86%). Deletions were detected for ATM (69%) and TP53 (31%), whereas i(8)(q10) was observed in 61% of cases. Mutations in ATM, TP53, JAK1 and JAK3 were detected in 73%, 14%, 6%, and 21% of patients, respectively. Additionally, BCOR mutations were observed for the first time in a lymphoid malignancy (8%). Two distinct genetic subgroups of T-PLL were identified: A large subset (86% of patients) showed abnormalities involving the TCRA/D locus activating the proto-oncogenes TCL1 or MTCP1, while the second group was characterized by a high frequency of TP53 mutations (4/7 cases). Further, analyses of overall survival identified JAK3 mutations as important prognostic marker, showing a significant negative impact.
2015-02-05 | GSE65649 | GEO
Project description:Missense mutations in CRX homeodomain cause dominant retinopathies through two distinct mechanisms
| PRJNA927048 | ENA
Project description:In this study, nonsense-mediated mRNA decay (NMD) inhibition was used for the discovery of truncating mutations. Six prostate cancer (PRCA) patients and their healthy brothers were selected from a group of HPCX1-linked families. mRNA was isolated from their lymphoblastic cells after pharmacological treatment. Expression analyses were done using Agilent 44K oligoarrays, and selected genes were screened for mutations by sequencing. In order to identify genes containing inactivating mutations in the Xq27-q28 region, an NMD microarray analysis with Agilent 44K Whole Human Genome oligonucleotide microarrays was performed in the families showing the strongest linkage to HPCX1. Five families were chosen with 6 affected and 6 healthy controls. Lymphoblastoid cell lines were derived from whole blood and treated with emetine to block NMD pathway. Total RNA was extracted from harvested cells (treated and untreated) and labeled with Cy5 and Cy3. Labeled samples were hybridized to the Agilent 44K Whole Human Genome Oligonucleotide Microarrays. After hybridization microarrays were scanned and data was extracted using Feature Extraction software. The candidate genes (n=17) for subsequent sequence analysis were selected according to the microarray analysis.
2011-12-31 | E-GEOD-24204 | biostudies-arrayexpress