Sequence variation between 462 human individuals fine-tunes functional sites of RNA processing

Ferreira, P. G., Oti, M., Barann, M., Wieland, T., Ezquina, S., Friedlander, M. R., Rivas, M. A., Esteve-Codina, A., Rosenstiel, Philip, Strom, T. M., Lappalainen, T., Guigo, R., Sammeth, M. and Consortium, Geuvadis (2016) Sequence variation between 462 human individuals fine-tunes functional sites of RNA processing Scientific Reports, 6 . DOI 10.1038/srep32406.

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Abstract

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.

Document Type: Article
Additional Information: Times Cited: 0 Ferreira, Pedro G. Oti, Martin Barann, Matthias Wieland, Thomas Ezquina, Suzana Friedlander, Marc R. Rivas, Manuel A. Esteve-Codina, Anna Rosenstiel, Philip Strom, Tim M. Lappalainen, Tuuli Guigo, Roderic Sammeth, Michael
Research affiliation: Kiel University
Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Refereed: Yes
DOI etc.: 10.1038/srep32406
ISSN: 2045-2322
Projects: Future Ocean
Date Deposited: 16 Mar 2017 08:39
Last Modified: 16 Mar 2017 08:39
URI: http://eprints.uni-kiel.de/id/eprint/36084

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