1,721,027 research outputs found
Helping young independent scientists: the EMBO Young Investigator Programme. Interview with Gerlind Wallon, Deputy Executive Director, EMBO Young Investigator Programme
No full textInterview with Professor Fotis C. Kafatos, President of the European Research Council
No full textThe European Research Council (ERC) is the first European funding body set up to support investigator-driven frontier research. Its main aim is to stimulate scientific excellence by supporting and encouraging the very best, truly creative scientists, scholars and engineers to be adventurous and take risks in their research. The scientists should go beyond the established frontiers of knowledge and the boundaries of disciplines. Being 'investigator-driven', or 'bottom-up', in nature, the ERC approach allows researchers to identify new opportunities and directions in any field of research. By challenging Europe's brightest minds, the ERC expects to bring about new and unpredictable scientific and technological discoveries-the kind that can form the basis of new industries, markets and broader social innovations of the future. Ultimately, the ERC aims to make the European research base more prepared to respond to the needs of a knowledge-based society and provide Europe with the capabilities in frontier research necessary to meet global challenges
Marie Curie fellowships unraveled. An interview with Theodosius Lennon, Director Directorate T, DG Research, European Commission
No full textThe Impact of Phenocopy on the Genetic Analysis of Complex Traits
Full text linkA consistent debate is ongoing on genome-wide association studies (GWAs). A key point is the capability to identify low-penetrance variations across the human genome. Among the phenomena reducing the power of these analyses, phenocopy level (PE) hampers very seriously the investigation of complex diseases, as well known in neurological disorders, cancer, and likely of primary importance in human ageing. PE seems to be the norm, rather than the exception, especially when considering the role of epigenetics and environmental factors towards phenotype. Despite some attempts, no recognized solution has been proposed, particularly to estimate the effects of phenocopies on the study planning or its analysis design. We present a simulation, where we attempt to define more precisely how phenocopy impacts on different analytical methods under different scenarios. With our approach the critical role of phenocopy emerges, and the more the PE level increases the more the initial difficulty in detecting gene-gene interactions is amplified. In particular, our results show that strong main effects are not hampered by the presence of an increasing amount of phenocopy in the study sample, despite progressively reducing the significance of the association, if the study is sufficiently powered. On the opposite, when purely epistatic effects are simulated, the capability of identifying the association depends on several parameters, such as the strength of the interaction between the polymorphic variants, the penetrance of the polymorphism and the alleles (minor or major) which produce the combined effect and their frequency in the population. We conclude that the neglect of the possible presence of phenocopies in complex traits heavily affects the analysis of their genetic data
PON1 is a longevity gene: results of a meta-analysis.
No full textParaoxonase 1 (PON1) is one of the most studied genes regarding cardiovascular risk, oxidative stress and inflammation. Several lines of evidence suggests that PON1 promotes an atheroprotective effect. Patients carrying PON1 codon 192 QQ genotype display a higher risk of cardiovascular events, the major cause of mortality in the elderly: it can be predicted that gene variants increasing the risk of mortality will be under-represented in long-living individuals. We first reported that PON1 R allele (R+) carriers are significantly more represented in Italian centenarians; subsequently this topic has been addressed by many other groups, and here we report a meta-analysis on 11 studies in different populations selected by a review of the literature available in PubMed and testing the effect of the Q192R polymorphism on human ageing. QUORUM guidelines for meta-analysis have been followed, and a total number of 5962 subjects have been included: 2795 young controls (65 years of age). The Mantel-Haenszel weighting for pooling in presence of a fixed effects model has been applied. The meta-analysis of R carriers showed a significant result with an overall OR of 1.16 (1.04-1.30, 95% CI, p = 0.006). The meta-analysis of QR genotype also showed a significant result, with an overall OR of 1.14 (1.02-1.27, 95% CI, p = 0.016). The results show that PON1 gene variants at codon 192 impact on the probability of attaining longevity, and that subjects carrying RR and QR genotypes (R+ carriers) are favoured in reaching extreme ages. These results likely represent the counterpart of the effects observed on cardiovascular diseases (CVD), as centenarians and nonagenarians escaped or delayed the onset of the major age-related diseases, including CVD. © 2009 Elsevier Ireland Ltd. All rights reserved
Network approaches to Genome-Wide association studies
No full textIn the framework of large-scale genotypic studies (describing the distribution of allele frequencies inside human genome) we characterize the Linkage Disequilibrium (LD) matrix as a network of relationships between alleles. We propose a suitable matrix discretization threshold, after a characterization of the distribution of noisy values inside LD matrix. We compare the main network parameters of a real LD matrix with two null models (Erdos-Renyi random network and a rewiring of the original network), in order to highlight the peculiar features of the LD network. We conclude stating the need of adequate computing tools for handling the high-dimensional data coming from Genome-Wide genotyping datasets
Role of mitochondrial DNA in longevity, aging and age-related diseases in humans: A reappraisal
No full textThe genetic variability of H. sapiens mitochondrial DNA (mtDNA) can be either germ-line inherited or somatically acquired, and its effect on aging and longevity as well as on the pathogenesis of complex age related diseases is a hot topic. Here we illustrate the complexity of such studies, related to the large genetic variability of mtDNA in different populations and the fact that the rate of the aging process is different in different cells, tissues and organs. As far as concern Alzheimer's disease, the accumulation of somatic mutations in several tissues have been investigated, as well as the inherited mtDNA variability. However, the issue is still controversial and further studies are needed to clarify the role of mtDNA variants in Alzheimer's disease. This review is aimed to summarize the most recent advances in this field. By high throughput mtDNA sequencing and the study of large cohorts of ethnically homogeneous subjects/patients, it is now possible to perform high dimensionality studies in order to clarify the genetic associations among several inherited mtDNA variants and longevity or age-associated diseases in humans
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