A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants

<p>Abstract</p> <p>Background</p> <p>Most human genes produce several transcripts with different exon contents by using alternative promoters, alternative polyadenylation sites and alternative splice sites. Much effort has been devoted to describing known gene transcripts through the development of numerous databases. Nevertheless, owing to the diversity of the transcriptome, there is a need for interactive databases that provide information about the potential function of each splicing variant, as well as its expression pattern.</p> <p>Description</p> <p>After setting up a database in which human and mouse splicing variants were compiled, we developed tools (1) to predict the production of protein isoforms from these transcripts, taking account of the presence of open reading frames and mechanisms that could potentially eliminate transcripts and/or inhibit their translation, i.e. nonsense-mediated mRNA decay and microRNAs; (2) to support studies of the regulation of transcript expression at multiple levels, including transcription and splicing, particularly in terms of tissue specificity; and (3) to assist in experimental analysis of the expression of splicing variants. Importantly, analyses of all features from transcript metabolism to functional protein domains were integrated in a highly interactive, user-friendly web interface that allows the functional and regulatory features of gene transcripts to be assessed rapidly and accurately.</p> <p>Conclusion</p> <p>In addition to identifying the transcripts produced by human and mouse genes, fast DB <url>http://www.fast-db.com</url> provides tools for analyzing the putative functions of these transcripts and the regulation of their expression. Therefore, fast DB has achieved an advance in alternative splicing databases by providing resources for the functional interpretation of splicing variants for the human and mouse genomes. Because gene expression studies are increasingly employed in clinical analyses, our web interface has been designed to be as user-friendly as possible and to be readily searchable and intelligible at a glance by the whole biomedical community.</p

Transcriptomic signatures across human tissues identify functional rare genetic variation

© 2020 American Association for the Advancement of Science. All rights reserved. INTRODUCTION: The human genome contains tens of thousands of rare (minor allele frequency 800 genomes matched with transcriptomes across 49 tissues, we were able to study RVs that underlie extreme changes in the transcriptome. To capture the diversity of these extreme changes, we developed and integrated approaches to identify expression, allele-specific expression, and alternative splicing outliers, and characterized the RV landscape underlying each outlier signal. We demonstrate that personal genome interpretation and RV discovery is enhanced by using these signals. This approach provides a new means to integrate a richer set of functional RVs into models of genetic burden, improve disease gene identification, and enable the delivery of precision genomics

Glycemia but not the Metabolic Syndrome is Associated with Cognitive Decline: Findings from the European Male Ageing Study

© 2017 American Association for Geriatric Psychiatry. Objective Previous research has indicated that components of the metabolic syndrome (MetS), such as hyperglycemia and hypertension, are negatively associated with cognition. However, evidence that MetS itself is related to cognitive performance has been inconsistent. This longitudinal study investigates whether MetS or its components affect cognitive decline in aging men and whether any interaction with inflammation exists. Methods Over a mean of 4.4 years (SD ± 0.3), men aged 40–79 years from the multicenter European Male Ageing Study were recruited. Cognitive functioning was assessed using the Rey-Osterrieth Complex Figure (ROCF), the Camden Topographical Recognition Memory (CTRM) task, and the Digit Symbol Substitution Test (DSST). High-sensitivity C-reactive protein (hs-CRP) levels were measured using a chemiluminescent immunometric assay. Results Overall, 1,913 participants contributed data to the ROCF analyses and 1,965 subjects contributed to the CTRM and DSST analyses. In multiple regression models the presence of baseline MetS was not associated with cognitive decline over time (p  >  0.05). However, logistic ordinal regressions indicated that high glucose levels were related to a greater risk of decline on the ROCF Copy (β = −0.42, p  <  0.05) and the DSST (β = −0.39, p  <  0.001). There was neither a main effect of hs-CRP levels nor an interaction effect of hs-CRP and MetS at baseline on cognitive decline. Conclusion No evidence was found for a relationship between MetS or inflammation and cognitive decline in this sample of aging men. However, glycemia was negatively associated with visuoconstructional abilities and processing speed

Sistema Tegumentario-ME141-201900

El curso Sistema Tegumentario revisa el desarrollo estructura función y disfunción de la piel. Las actividades de aprendizaje realizan una revisión de los fundamentos del sistema tegumentario y de sus patologías más frecuentes. Curso de especialidad en la carrera de Medicina de carácter teórico práctico dirigido a los estudiantes del segundo nivel de la malla curricular busca desarrollar la competencia específica de Profesionalismo ¿ Aprendizaje autónomo y desarrollo profesional. Este curso brinda las bases de la práctica clínica y en los cursos siguientes se desarrolle la competencia de diagnóstico prevención y promoción

Sistema Tegumentario - ME141 201900

El curso Sistema Tegumentario revisa el desarrollo, estructura, función y disfunción de la piel. Las actividades de aprendizaje realizan una revisión de los fundamentos del sistema tegumentario y de sus patologías más frecuentes. Curso de especialidad en la carrera de Medicina, de carácter teórico práctico dirigido a los estudiantes del segundo nivel de la malla curricular, busca desarrollar la competencia específica de Profesionalismo ¿ Aprendizaje autónomo y desarrollo profesional. Este curso brinda las bases de la práctica clínica y en los cursos siguientes se desarrolle la competencia de diagnóstico, prevención y promoción

PLMdetect: a bioinformatic approach to identify cis-regulatory motifs in promoters of Plant genomes.

International audienc

The Transposable Element Environment of Human Genes Differs According to Their Duplication Status and Essentiality

International audienceTransposable elements (TEs) are major components of eukaryotic genomes and represent approximately 45% of the human genome. TEs can be important sources of novelty in genomes and there is increasing evidence that TEs contribute to the evolution of gene regulation in mammals. Gene duplication is an evolutionary mechanism that also provides new genetic material and opportunities to acquire new functions. To investigate how duplicated genes are maintained in genomes, here, we explored the TE environment of duplicated and singleton genes. We found that singleton genes have more short-interspersed nuclear elements and DNA transposons in their vicinity than duplicated genes, whereas long-interspersed nuclear elements and long-terminal repeat retrotransposons have accumulated more near duplicated genes. We also discovered that this result is highly associated with the degree of essentiality of the genes with an unexpected accumulation of short-interspersed nuclear elements and DNA transposons around the more-essential genes. Our results underline the importance of taking into account the TE environment of genes to better understand how duplicated genes are maintained in genomes