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

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Ferreira , P G , Oti , M , Barann , M , Wieland , T , Ezquina , S , Friedlander , M R , Rivas , M A , Esteve-Codina , A , Rosenstiel , P , Strom , T M , Lappalainen , T , Guigo , R , Sammeth , M , GEUVADIS Consortium & Palotie , A 2016 , ' Sequence variation between 462 human individuals fine-tunes functional sites of RNA processing ' , Scientific Reports , vol. 6 , 32406 . https://doi.org/10.1038/srep32406

Title: Sequence variation between 462 human individuals fine-tunes functional sites of RNA processing
Author: 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; GEUVADIS Consortium; Palotie, A.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2016-09-12
Language: eng
Number of pages: 13
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/174554
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.
Subject: PRE-MESSENGER-RNA
HUMAN GENE-EXPRESSION
HUMAN GENOME
SPLICE-SITE
EDITING SITES
HUMAN-DISEASE
POLYADENYLATION
TRANSCRIPTOME
MECHANISMS
POPULATION
3111 Biomedicine
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