Transcriptome and genome sequencing uncovers functional variation in humans

Tuuli Lappalainen, Michael Sammeth, Marc R. Friedländer, Peter A C 'T Hoen, Jean Monlong, Manuel A. Rivas, Mar Gonzàlez-Porta, Natalja Kurbatova, Thasso Griebel, Pedro G. Ferreira, Matthias Barann, Thomas Wieland, Liliana Greger, Maarten Van Iterson, Jonas Almlöf, Paolo Ribeca, Irina Pulyakhina, Daniela Esser, Thomas Giger, Andrew Tikhonov & 37 others Marc Sultan, Gabrielle Bertier, Daniel G. Macarthur, Monkol Lek, Esther Lizano, Henk P J Buermans, Ismael Padioleau, Thomas Schwarzmayr, Olof Karlberg, Halit Ongen, Helena Kilpinen, Sergi Beltran, Marta Gut, Katja Kahlem, Vyacheslav Amstislavskiy, Oliver Stegle, Matti Pirinen, Stephen B. Montgomery, Peter Donnelly, Mark I. McCarthy, Paul Flicek, Tim M. Strom, Hans Lehrach, Stefan Schreiber, Ralf Sudbrak, Ángel Carracedo, Stylianos E. Antonarakis, Robert Häsler, Ann Christine Syvänen, Gert Jan Van Ommen, Alvis Brazma, Thomas Meitinger, Philip Rosenstiel, Roderic Guigó, Ivo G. Gut, Xavier P. Estivill, Emmanouil T. Dermitzakis

Research output: Contribution to journalArticle

777 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)506-511
Number of pages6
JournalNature
Volume501
Issue number7468
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Transcriptome
High-Throughput Nucleotide Sequencing
Genome
Human Genome
MicroRNAs
Cell Line
Messenger RNA
Population
Genes

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Lappalainen, T., Sammeth, M., Friedländer, M. R., 'T Hoen, P. A. C., Monlong, J., Rivas, M. A., ... Dermitzakis, E. T. (2013). Transcriptome and genome sequencing uncovers functional variation in humans. Nature, 501(7468), 506-511. https://doi.org/10.1038/nature12531

Transcriptome and genome sequencing uncovers functional variation in humans. / Lappalainen, Tuuli; Sammeth, Michael; Friedländer, Marc R.; 'T Hoen, Peter A C; Monlong, Jean; Rivas, Manuel A.; Gonzàlez-Porta, Mar; Kurbatova, Natalja; Griebel, Thasso; Ferreira, Pedro G.; Barann, Matthias; Wieland, Thomas; Greger, Liliana; Van Iterson, Maarten; Almlöf, Jonas; Ribeca, Paolo; Pulyakhina, Irina; Esser, Daniela; Giger, Thomas; Tikhonov, Andrew; Sultan, Marc; Bertier, Gabrielle; Macarthur, Daniel G.; Lek, Monkol; Lizano, Esther; Buermans, Henk P J; Padioleau, Ismael; Schwarzmayr, Thomas; Karlberg, Olof; Ongen, Halit; Kilpinen, Helena; Beltran, Sergi; Gut, Marta; Kahlem, Katja; Amstislavskiy, Vyacheslav; Stegle, Oliver; Pirinen, Matti; Montgomery, Stephen B.; Donnelly, Peter; McCarthy, Mark I.; Flicek, Paul; Strom, Tim M.; Lehrach, Hans; Schreiber, Stefan; Sudbrak, Ralf; Carracedo, Ángel; Antonarakis, Stylianos E.; Häsler, Robert; Syvänen, Ann Christine; Van Ommen, Gert Jan; Brazma, Alvis; Meitinger, Thomas; Rosenstiel, Philip; Guigó, Roderic; Gut, Ivo G.; Estivill, Xavier P.; Dermitzakis, Emmanouil T.

In: Nature, Vol. 501, No. 7468, 2013, p. 506-511.

Research output: Contribution to journalArticle

Lappalainen, T, Sammeth, M, Friedländer, MR, 'T Hoen, PAC, Monlong, J, Rivas, MA, Gonzàlez-Porta, M, Kurbatova, N, Griebel, T, Ferreira, PG, Barann, M, Wieland, T, Greger, L, Van Iterson, M, Almlöf, J, Ribeca, P, Pulyakhina, I, Esser, D, Giger, T, Tikhonov, A, Sultan, M, Bertier, G, Macarthur, DG, Lek, M, Lizano, E, Buermans, HPJ, Padioleau, I, Schwarzmayr, T, Karlberg, O, Ongen, H, Kilpinen, H, Beltran, S, Gut, M, Kahlem, K, Amstislavskiy, V, Stegle, O, Pirinen, M, Montgomery, SB, Donnelly, P, McCarthy, MI, Flicek, P, Strom, TM, Lehrach, H, Schreiber, S, Sudbrak, R, Carracedo, Á, Antonarakis, SE, Häsler, R, Syvänen, AC, Van Ommen, GJ, Brazma, A, Meitinger, T, Rosenstiel, P, Guigó, R, Gut, IG, Estivill, XP & Dermitzakis, ET 2013, 'Transcriptome and genome sequencing uncovers functional variation in humans', Nature, vol. 501, no. 7468, pp. 506-511. https://doi.org/10.1038/nature12531
Lappalainen T, Sammeth M, Friedländer MR, 'T Hoen PAC, Monlong J, Rivas MA et al. Transcriptome and genome sequencing uncovers functional variation in humans. Nature. 2013;501(7468):506-511. https://doi.org/10.1038/nature12531
Lappalainen, Tuuli ; Sammeth, Michael ; Friedländer, Marc R. ; 'T Hoen, Peter A C ; Monlong, Jean ; Rivas, Manuel A. ; Gonzàlez-Porta, Mar ; Kurbatova, Natalja ; Griebel, Thasso ; Ferreira, Pedro G. ; Barann, Matthias ; Wieland, Thomas ; Greger, Liliana ; Van Iterson, Maarten ; Almlöf, Jonas ; Ribeca, Paolo ; Pulyakhina, Irina ; Esser, Daniela ; Giger, Thomas ; Tikhonov, Andrew ; Sultan, Marc ; Bertier, Gabrielle ; Macarthur, Daniel G. ; Lek, Monkol ; Lizano, Esther ; Buermans, Henk P J ; Padioleau, Ismael ; Schwarzmayr, Thomas ; Karlberg, Olof ; Ongen, Halit ; Kilpinen, Helena ; Beltran, Sergi ; Gut, Marta ; Kahlem, Katja ; Amstislavskiy, Vyacheslav ; Stegle, Oliver ; Pirinen, Matti ; Montgomery, Stephen B. ; Donnelly, Peter ; McCarthy, Mark I. ; Flicek, Paul ; Strom, Tim M. ; Lehrach, Hans ; Schreiber, Stefan ; Sudbrak, Ralf ; Carracedo, Ángel ; Antonarakis, Stylianos E. ; Häsler, Robert ; Syvänen, Ann Christine ; Van Ommen, Gert Jan ; Brazma, Alvis ; Meitinger, Thomas ; Rosenstiel, Philip ; Guigó, Roderic ; Gut, Ivo G. ; Estivill, Xavier P. ; Dermitzakis, Emmanouil T. / Transcriptome and genome sequencing uncovers functional variation in humans. In: Nature. 2013 ; Vol. 501, No. 7468. pp. 506-511.
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