Transcriptome and genome sequencing uncovers functional variation in humans

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Lappalainen, T (Author) Other; Sammeth, M (Author) Other; Friedländer, MR (Author) Other; `t Hoen, PAC (Author) Other; Monlong, J (Author) Other; Rivas, MA (Author) Other; Gonzàlez-Porta, M (Author) Other; Kurbatova, N (Author) Other; Griebel, T (Author) Other; Ferreira, PG (Author) Other; Barann, M (Author) Other; Wieland, T (Author) Other; Greger, L (Author) Other; van Iterson, M (Author) Other; Almlöf, J (Author) Other; Ribeca, P (Author) Other; Pulyakhina, I (Author) Other; Esser, D (Author) Other; Giger, T (Author) Other; Tikhonov, A (Author) Other; Sultan, M (Author) Other; Bertier, G (Author) Other; MacArthur, DG (Author) Other; Lek, M (Author) Other; Lizano, E (Author) Other; Buermans, HPJ (Author) Other; Padioleau, I (Author) Other; Schwarzmayr, T (Author) Other; Karlberg, O (Author) Other; Ongen, H (Author) Other; Kilpinen, H (Author) Other; Beltran, S (Author) Other; Gut, M (Author) Other; Kahlem, K (Author) Other; Amstislavskiy, V (Author) Other; Stegle, O (Author) Other; Pirinen, M (Author) Other; Montgomery, SB (Author) Other; Donnelly, P (Author) Other; McCarthy, MI (Author) Other; Flicek, P (Author) Other; Strom, TM (Author) Other; The Geuvadis Consortium, (Author) Other; Lehrach, H (Author) Other; Schreiber, S (Author) Other; Sudbrak, R (Author) Other; Carracedo, (Author) Other; Antonarakis, SE (Author) Other; Häsler, R (Author) Other; Syvänen, A (Author) Other; van Ommen, G (Author) Other; Brazma, A (Author) Other; Meitinger, T (Author) Other; Rosenstiel, P (Author) Other; Guigó, R (Author) Other; Gut, IG (Author) Other; Estivill, X (Author) Other; Dermitzakis, ET (Author) Other

Journal

Title: Nature

Vol. 501

Pages: 506-511

ISSN: 0028-0836

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 1085 Citations

Scopus - 1097 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-00F-Y0S

DOI: 10.1038/nature12531

Abstract (EN): Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project-the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6