1,721,417 research outputs found
Bell (Christopher) : Portugal and the Quest for the Indies
No full textRichon Louis. Bell (Christopher) : Portugal and the Quest for the Indies. In: Revue française d'histoire d'outre-mer, tome 61, n°225, 4e trimestre 1974. p. 596
Bell (Christopher) : Portugal and the Quest for the Indies
No full textRichon Louis. Bell (Christopher) : Portugal and the Quest for the Indies. In: Revue française d'histoire d'outre-mer, tome 61, n°225, 4e trimestre 1974. p. 596
Insights in human epigenomic dynamics through comparative primate analysis
No full textEpigenomic analysis gives a molecular insight into cell-specific genomic activity. It provides a detailed functional plan to dissect an organism, tissue by tissue. Therefore comparative epigenomics may increase understanding of human-acquired traits, by revealing regulatory changes in systems such as the neurological, musculoskeletal, and immunological.Enhancer loci evolve fast by hijacking elements from other tissues or rewiring and amplifying existing units for human-specific function. Promoters by contrast often require a CpG dense genetic infrastructure. Specific interplay occurs between the two, but also a shared modality of function, with coordination from global chromatin-modifying enzymes. Changes in specific transcription factor binding sites also facilitate the local epigenetic state. In the case of CTCF, these may further influence 3-dimensional structure and interaction.How these mechanistic units are modulated between tissue and species enables more comprehensive understanding of human processes and pathology. With this information, precise therapeutic targeting of these epigenetic modifications may become possible
Accessing and selecting genetic markers from available resources
No full textThe history of genetic markers accurately partitions the progression of molecular genetics into three phases: the RFLP (restriction fragment length polymorphism), microsatellite and SNP (single nucleotide polymorphism) eras. This chapter focuses predominately on the current workhorse, the SNP, though briefly covers the former two and overviews current online databases and portals that act as central repositories as well as hubs to further detailed information. Central gene or disease-based searches are considered and then followed through systematicall
Integration of genomic and epigenomic DNA methylation data in common complex diseases by haplotype-specific methylation analysis
No full textThe analysis of complex diseases was revolutionized by the ability to genotype at a genome-wide level tagging common SNPs in sufficiently large, and therefore adequately powered, population sample sets. This technological breakthrough has led to thousands of genetic variants being robustly associated with a multitude of phenotypic traits. These findings have illuminated novel genes and previously unknown pathways in the pathogenesis of disease, although in the majority of loci the functional mechanism remains unknown. The integration of this genomic information with epigenomic and transcriptomic data from these regions is one of the next steps in unraveling their biological significance. Allele-specific methylation influences allele-specific expression; therefore, the methylation state of the haplotypes within genetically associated regions can determine epigenetic differences with potential functional effects. DNA methylation data and association-determined risk and nonrisk haplotypes can be compared by a haplotype-specific methylation analysis. These are the first forays into what will become an increasingly routine multidimensional analysis as whole-genome, epigenome and transcriptome sequencing data become easily obtainable, with existing second- and soon to be available third-generation sequencing analyzers. Concise understanding of the functional implications of these genome-wide association-derived risk factors, plus rare variants discovered from deep sequencing experiments currently underway, will enable personalized risk and prevention profiling, as well as treatment, to come to fruition
The epigenomic analysis of human obesity
No full textThe epigenome - the chemical modifications and packaging of the genome that can influence or indicate its activity - gives a molecular insight to cell-type specific workings. It can, therefore, reveal the pathophysiological mechanisms at work in disease. Detected changes can also represent physiological responses to adverse environmental exposures, thus enabling the epigenetic mark of DNA methylation to act as an epidemiological biomarker, even in surrogate tissue.This makes epigenomic analysis an attractive prospect to further understand the pathobiology and epidemiological aspects of obesity. Furthermore, integrating epigenomic data with known obesity-associated common genetic variation can aid in deciphering their molecular mechanisms.This review primarily examines epidemiological or population-based studies of epigenetic modifications in relation to adiposity-traits, as opposed to animal or cell models. It discusses recent work exploring the epigenome with respect to human obesity, which to date have predominately been array-based studies of DNA methylation in peripheral blood. It is of note that highly replicated BMI DNA methylation associations are not causal, but strongly driven by co-associations for more precisely measured intertwined outcomes and factors, such as hyperlipidaemia, hyperglycaemia and inflammation. Finally, the potential for the future exploration of the epigenome in obesity and related disorders will be considered.<br/
The epigenomic interface between genome and environment in common complex diseases
No full textThe epigenome plays the pivotal role as interface between genome and environment. True genome-wide assessments of epigenetic marks, such as DNA methylation (methylomes) or chromatin modifications (chromatinomes), are now possible, either through high-throughput arrays or increasingly by second-generation DNA sequencing methods. The ability to collect these data at this level of resolution enables us to begin to be able to propose detailed questions, and interrogate this information, with regards to changes that occur due to development, lineage and tissue-specificity, and significantly those caused by environmental influence, such as ageing, stress, diet, hormones or toxins. Common complex traits are under variable levels of genetic influence and additionally epigenetic effect. The detection of pathological epigenetic alterations will reveal additional insights into their aetiology and how possible environmental modulation of this mechanism may occur. Due to the reversibility of these marks, the potential for sequence-specific targeted therapeutics exists. This review surveys recent epigenomic advances and their current and prospective application to the study of common disease
Advances in the identification and analysis of allele-specific expression
Full text linkAllele-specific expression (ASE) is essential for normal development and many cellular processes but, if impaired, can result in disease. ASE is a feature of organisms with genomes consisting of more than one set of homologous chromosomes. The higher the number of chromosome sets (ploidy) per cell, the higher the potential complexity of ASE. Humans, for instance, are diploid (except germ cells, which are haploid), resulting in multiple possible expression states in time and space for each set of alleles. ASE is invoked and modulated by both genetic and epigenetic changes, affecting the underlying DNA sequence or chromatin of each allele, respectively. Although numerous methods have been developed to assay ASE, they usually require RNA to be available and are dependent upon genetic polymorphisms (such as single nucleotide polymorphisms (SNPs)) to differentiate between allelic transcripts. The rapid convergence to second-generation sequencing as the method of choice to examine genomic, epigenomic and transcriptomic data enables an integrated and more general approach to define and predict ASE, independent of SNPs. This 'Omni-Seq' approach has the potential to advance our understanding of the biology and pathophysiology of ASE-mediated processes by elucidating subtle combinatorial effects, leading to the accurate delineation of sub-phenotypes with consequential benefit for improved insight into disease etiology
- …
