Sequence variation between 462 human individuals fine-tunes functional sites of RNA processing
Ferreira, Pedro G. (Centre de Regulació Genòmica)
Oti, Martin (Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho)
Barann, Matthias (Christians-Albrechts-Universität zu Kiel. Institute of Clinical Molecular Biology)
Wieland, Thomas (Helmholtz Center Munich. Institute of Human Genetics)
Ezquina, Suzana (University of São Paulo. Center for Human Genome and Stem-cell research)
Friedländer, Marc R. (Stockholm University. Science for Life Laboratory)
Rivas, Manuel A. (University of Oxford. Wellcome Trust Centre for Human Genetics)
Esteve-Codina, Anna (Centre de Recerca en Agrigenòmica)
Rosenstiel, Philip (Christians-Albrechts-Universität zu Kiel. Institute of Clinical Molecular Biology)
Strom, Tim M. (Technische Universität München. Institute of Human Genetics)
Lappalainen, Tuuli (University of Geneva. Institute for Genetics and Genomics in Geneva)
Guigó, Roderic (Universitat Pompeu Fabra)
Sammeth, Michael (National Center of Scientific Computing (Brazil))

Data:	2016
Resum:	Recent advances in the cost-efficiency of sequencing technologies enabled the combined DNA- and RNA-sequencing of human individuals at the population-scale, making genome-wide investigations of the inter-individual genetic impact on gene expression viable. Employing mRNA-sequencing data from the Geuvadis Project and genome sequencing data from the 1000 Genomes Project we show that the computational analysis of DNA sequences around splice sites and poly-A signals is able to explain several observations in the phenotype data. In contrast to widespread assessments of statistically significant associations between DNA polymorphisms and quantitative traits, we developed a computational tool to pinpoint the molecular mechanisms by which genetic markers drive variation in RNA-processing, cataloguing and classifying alleles that change the affinity of core RNA elements to their recognizing factors. The in silico models we employ further suggest RNA editing can moonlight as a splicing-modulator, albeit less frequently than genomic sequence diversity. Beyond existing annotations, we demonstrate that the ultra-high resolution of RNA-Seq combined from 462 individuals also provides evidence for thousands of bona fide novel elements of RNA processing-alternative splice sites, introns, and cleavage sites-which are often rare and lowly expressed but in other characteristics similar to their annotated counterparts.
Ajuts:	European Commission 261123
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cell biology ; Computational biology and bioinformatics ; Molecular biology
Publicat a:	Scientific reports, Vol. 6 (September 2016) , art. 32406, ISSN 2045-2322

DOI: 10.1038/srep32406
PMID: 27617755

13 p, 1.3 MB

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