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

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Ferreira, PG (Author) Other; Oti, M (Author) Other; Barann, M (Author) Other; Wieland, T (Author) Other; Ezquina, S (Author) Other; Friedländer, MR (Author) Other; Rivas, MA (Author) Other; Esteve-Codina, A (Author) Other; Estivill, X (Author) Other; Guigó, R (Author) Other; Dermitzakis, E (Author) Other; Antonarakis, S (Author) Other; Meitinger, T (Author) Other; Strom, TM (Author) Other; Palotie, A (Author) Other; François Deleuze, J (Author) Other; Sudbrak, R (Author) Other; Lerach, H (Author) Other; Gut, I (Author) Other; Syvänen, A (Author) Other; Gyllensten, U (Author) Other; Schreiber, S (Author) Other; Rosenstiel, P (Author) Other; Brunner, H (Author) Other; Veltman, J (Author) Other; Hoen, PA (Author) Other; Jan van Ommen, G (Author) Other; Carracedo, A (Author) Other; Brazma, A (Author) Other; Flicek, P (Author) Other; Cambon-Thomsen, A (Author) Other; Mangion, J (Author) Other; Bentley, D (Author) Other; Hamosh, A (Author) Other; Rosenstiel, P (Author) Other; Strom, TM (Author) Other; Lappalainen, T (Author) Other; Guigó, R (Author) Other; Sammeth, M (Author) Other

Journal

Title: Scientific Reports

Vol. 6

ISSN: 2045-2322

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 12 Citations

Scientific classification

CORDIS: Natural sciences > Biological sciences > Biology > Computational biology

FOS: Natural sciences > Biological sciences ; Natural sciences > Computer and information sciences

Other information

Authenticus ID: P-00K-VDJ

DOI: 10.1038/srep32406

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13