Search results for "genetics [Spliceosomes]"

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci ass…

miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression.

2009

BackgroundIn humans and mice naturally occurring CD4(+)CD25(+) regulatory T cells (nTregs) are a thymus-derived subset of T cells, crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Recent work using Dicer-deficient mice irrevocably demonstrated the importance of miRNAs for nTreg cell-mediated tolerance.Principal findingsDNA-Microarray analyses of human as well as murine conventional CD4(+) Th cells and nTregs revealed a strong up-regulation of mature miR-155 (microRNA-155) upon activation in both populations. Studying miR-155 expression in FoxP3-deficient scurfy mice …

X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

2021

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds…

FOXP2 gene and language impairment in schizophrenia: association and epigenetic studies

2010

Abstract Background Schizophrenia is considered a language related human specific disease. Previous studies have reported evidence of positive selection for schizophrenia-associated genes specific to the human lineage. FOXP2 shows two important features as a convincing candidate gene for schizophrenia vulnerability: FOXP2 is the first gene related to a language disorder, and it has been subject to positive selection in the human lineage. Methods Twenty-seven SNPs of FOXP2 were genotyped in a cohort of 293 patients with schizophrenia and 340 controls. We analyzed in particular the association with the poverty of speech and the intensity of auditory hallucinations. Potential expansion of thre…

Acetic acid and acidification accelerate chronological and replicative aging in yeast

2012

Yeast is widely regarded as one of the most valuable model systems to study aging and particularly the genetics of aging. Researchers have established two different methods to study yeast aging known as the replicative lifespan (RLS) and the chronological lifespan (CLS). These have led to the identification of many mammalian genes that affect aging suggesting that they will continue to shed light on the fundamental biology of aging. In spite of the clear differences underpinning the mitotic cellular potential (RLS) and the survival in the non-dividing mode (CLS), the two models are clearly regulated by partly overlapping regulatory mechanism. This idea is supported by the observation that c…

AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity.

2010

The CB1 cannabinoid receptor is the most abundant G-protein coupled receptor in the brain and a key regulator of neuronal excitability. There is strong evidence that CB1 receptor on glutamatergic hippocampal neurons is beneficial to alleviate epileptiform seizures in mouse and man. Therefore, we hypothesized that experimentally increased CB1 gene dosage in principal neurons would have therapeutic effects in kainic acid (KA)-induced hippocampal pathogenesis. Here, we show that virus-mediated conditional overexpression of CB1 receptor in pyramidal and mossy cells of the hippocampus is neuroprotective and moderates convulsions in the acute KA seizure model in mice. We introduce a recombinant a…

Application of model quality evaluation to systems biology

2008

Application of model quality evaluation to the quasispecies models is presented. These models are useful for the analysis of the DNA and RNA evolution and for the description of the population dynamics of viruses and bacteria. An estimate of the parameters together with their interval of variability is computed and the quality evaluation is tested on the basis of the model prediction error capability.

Addressing the gap between genetics knowledge and clinical practice: a pilot study to implement genetics education among physicians in Italy

2012

As a result of large investments in basic science, the genomic discoveries have brought outstanding advances in understanding the molecular basis of human health. Hundreds of genes whose variations contribute to human diseases, or patients’ responses to drug treatments or even to vaccination have been discovered, laying the foundation for a paradigm shift in healthcare...

178 – Promoter region of foxp2 gene: epigenetic and evolutionary analysis

2008

Methyl-CpG-binding proteins

2000

CpG methylation, the most common epigenetic modification of vertebrate genomes, is primarily associated with transcriptional repression. MeCP2, MBD1, MBD2, MBD3 and MBD4 constitute a family of vertebrate proteins that share the methyl-CpG-binding domain (MBD). The MBD, consisting of about 70 residues, possesses a unique alpha/beta-sandwich structure with characteristic loops, and is able to bind single methylated CpG pairs as a monomer. All MBDs except MBD4, an endonuclease that forms a complex with the DNA mismatch-repair protein MLH1, form complexes with histone deacetylase. It has been established that MeCP2, MBD1 and MBD2 are involved in histone deacetylase-dependent repression and it i…