Effect of predicted protein-truncating genetic variants on the human transcriptome
Author:
Rivas Manuel A.1, Pirinen Matti2, Conrad Donald F.3, Lek Monkol45, Tsang Emily K.678, Karczewski Konrad J.45, Maller Julian B.45, Kukurba Kimberly R.67, DeLuca David S.4, Fromer Menachem459, Ferreira Pedro G.101112, Smith Kevin S.67, Zhang Rui6, Zhao Fengmei45, Banks Eric4, Poplin Ryan4, Ruderfer Douglas M.913, Purcell Shaun M.45913, Tukiainen Taru45, Minikel Eric V.45, Stenson Peter D.14, Cooper David N.14, Huang Katharine H.4, Sullivan Timothy J.4, Nedzel Jared4, Bustamante Carlos D.6, Li Jin Billy6, Daly Mark J.45, Guigo Roderic15, Donnelly Peter116, Ardlie Kristin4, Sammeth Michael1517, Dermitzakis Emmanouil T.101112, McCarthy Mark I.118, Montgomery Stephen B.67, Lappalainen Tuuli610111219, MacArthur Daniel G.4520, Segre Ayellet V., Young Taylor R., Gelfand Ellen T., Trowbridge Casandra A., Ward Lucas D., Kheradpour Pouya, Iriarte Benjamin, Meng Yan, Palmer Cameron D., Esko Tonu, Winckler Wendy, Hirschhorn Joel, Kellis Manolis, Getz Gad, Shablin Andrey A., Li Gen, Zhou Yi-Hui, Nobel Andrew B., Rusyn Ivan, Wright Fred A., Battle Alexis, Mostafavi Sara, Mele Marta, Reverter Ferran, Goldmann Jakob, Koller Daphne, Gamazon Eric R., Im Hae Kyung, Konkashbaev Anuar, Nicolae Dan L., Cox Nancy J., Flutre Timothe, Wen Xiaoquan, Stephens Matthew, Pritchard Jonathan K., Tu Zhidong, Zhang Bin, Huang Tao, Long Quan, Lin Luan, Yang Jialiang, Zhu Jun, Liu Jun, Brown Amanda, Mestichelli Bernadette, Tidwell Denee, Lo Edmund, Salvatore Mike, Shad Saboor, Thomas Jeffrey A., Lonsdale John T., Choi Roswell Christopher, Karasik Ellen, Ramsey Kimberly, Moser Michael T., Foster Barbara A., Gillard Bryan M., Syron John, Fleming Johnelle, Magazine Harold, Hasz Rick, Walters Gary D., Bridge Jason P., Miklos Mark, Sullivan Susan, Barker Laura K., Traino Heather, Mosavel Magboeba, Siminoff Laura A., Valley Dana R., Rohrer Daniel C., Jewel Scott, Branton Philip, Sobin Leslie H., Barcus Mary, Qi Liqun, Hariharan Pushpa, Wu Shenpei, Tabor David, Shive Charles, Smith Anna M., Buia Stephen A., Undale Anita H., Robinson Karna L., Roche Nancy, Valentino Kimberly M., Britton Angela, Burges Robin, Bradbury Debra, Hambright Kenneth W., Seleski John, Korzeniewski Greg E., Erickson Kenyon, Marcus Yvonne, Tejada Jorge, Taherian Mehran, Lu Chunrong, Robles Barnaby E., Basile Margaret, Mash Deborah C., Volpi Simona, Struewing Jeffery P., Temple Gary F., Boyer Joy, Colantuoni Deborah, Little Roger, Koester Susan, Carithers Latarsha J., Moore Helen M., Guan Ping, Compton Carolyn, Sawyer Sherilyn J., Demchok Joanne P., Vaught Jimmie B., Rabiner Chana A., Lockhart Nicole C., Friedlander Marc R., ’t Hoen Peter A. C., Monlong Jean, Gonzàlez-Porta Mar, Kurbatova Natalja, Griebel Thasso, Barann Matthias, Wieland Thomas, Greger Liliana, van Iterson Maarten, Almlof Jonas, Ribeca Paolo, Pulyakhina Irina, Esser Daniela, Giger Thomas, Tikhonov Andrew, Sultan Marc, Bertier Gabrielle, 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, Flicek Paul, Strom Tim M., Lehrach Hans, Schreiber Stefan, Sudbrak Ralf, Carracedo Angel, Antonarakis Stylianos E., Hasler Robert, Syvanen Ann-Christine, van Ommen Gert-Jan, Brazma Alvis, Meitinger Thomas, Rosenstiel Philip, Gut Ivo G., Estivill Xavier, ,
Affiliation:
1. Wellcome Trust Centre for Human Genetics, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. 2. FInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. 3. Washington University in St. Louis, St. Louis, MO, USA. 4. Broad Institute of MIT and Harvard, Cambridge, MA, USA. 5. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. 6. Department of Genetics, Stanford University, Stanford, CA, USA. 7. Department of Pathology, Stanford University, Stanford, CA, USA. 8. Biomedical Informatics Program, Stanford University, Stanford, CA, USA. 9. Department of Psychiatry, Mt. Sinai Hospital, NY, USA. 10. Department of Genetic Medicine and Development,University of Geneva, Geneva, Switzerland. 11. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. 12. Swiss Institute of Bioinformatics, Geneva, Switzerland. 13. Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, NY, USA. 14. Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, UK. 15. Center for Genomic Regulation (CRG), Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. 16. Department of Statistics, University of Oxford, Oxford, UK. 17. National Institute for Scientific Computing (LNCC), Petropolis, Rio de Janeiro, Brazil. 18. Oxford Center for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK. 19. New York Genome Center, New York, NY, USA. 20. Department of Medicine, Harvard Medical School, Boston, MA, USA.
Abstract
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
Funder
National Institutes of Health United States Department of Defense Wellcome Trust European Research Council Natural Science and Engineering Research Council of Canada University of Oxford Louis-Jeantet Foundation Swiss National Science Foundation Academy of Finland Clarendon Scholarship NDM Studentship
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Multidisciplinary
Cited by
258 articles.
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