The human transcriptome across tissues and individuals

By Marta Melé, Pedro G. Ferreira, Ferran Reverter, D. DeLuca, Jean Monlong, M. Sammeth, Taylor R. Young, Jakob M. Goldmann, Dmitri D. Pervouchine, Timothy J. Sullivan and 11 more. Science, 2015

1,238 citations recorded by the source corpus.

Expression, genetic variation, and tissues Human genomes show extensive genetic variation across individuals, but we have only just started documenting the effects of this variation on the regulation of gene expression. Furthermore, only a few tissues have been examined per genetic variant. In order to examine how genetic expression varies among tissues within individuals, the Genotype-Tissue Expression (GTEx) Consortium collected 1641 postmortem samples covering 54 body sites from 175 individuals. They identified quantitative genetic traits that affect gene expression and determined which of these exhibit tissue-specific expression patterns. Melé et al. measured how transcription varies among tissues, and Rivas et al. looked at how truncated protein variants affect expression across tissues. Science, this issue p. 648, p. 660, p. 666; see also p. 640 RNA expression documents patterns of human transcriptome variation across individuals and tissues. [Also see Perspective by Gibson] Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes—which is most clearly seen in blood—though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0e166790fb686d43bb6983800d05c38766c79d39

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Citations in the corpus

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