Effect of predicted protein-truncating genetic variants on the human transcriptome

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Rivas, MA (Author) Other; Pirinen, M (Author) Other; Conrad, DF (Author) Other; Lek, M (Author) Other; Tsang, EK (Author) Other; Karczewski, KJ (Author) Other; Maller, JB (Author) Other; Kukurba, KR (Author) Other; DeLuca, DS (Author) Other; Fromer, M (Author) Other; Ferreira, PG (Author) Other; Smith, KS (Author) Other; Zhang, R (Author) Other; Zhao, F (Author) Other; Banks, E (Author) Other; Poplin, R (Author) Other; Ruderfer, DM (Author) Other; Purcell, SM (Author) Other; Tukiainen, T (Author) Other; Minikel, EV (Author) Other; Stenson, PD (Author) Other; Cooper, DN (Author) Other; Huang, KH (Author) Other; Sullivan, TJ (Author) Other; Nedzel, J (Author) Other; Bustamante, CD (Author) Other; Li, JB (Author) Other; Daly, MJ (Author) Other; Guigo, R (Author) Other; Donnelly, P (Author) Other; Ardlie, K (Author) Other; Sammeth, M (Author) Other; Dermitzakis, ET (Author) Other; McCarthy, MI (Author) Other; Montgomery, SB (Author) Other; Lappalainen, T (Author) Other; MacArthur, DG (Author) Other; Segre, AV (Author) Other; Young, TR (Author) Other; Gelfand, ET (Author) Other; Trowbridge, CA (Author) Other; Ward, LD (Author) Other; Kheradpour, P (Author) Other; Iriarte, B (Author) Other; Meng, Y (Author) Other; Palmer, CD (Author) Other; Esko, T (Author) Other; Winckler, W (Author) Other; Hirschhorn, J (Author) Other; Kellis, M (Author) Other; Getz, G (Author) Other; Shablin, AA (Author) Other; Li, G (Author) Other; Zhou, Y (Author) Other; Nobel, AB (Author) Other; Rusyn, I (Author) Other; Wright, FA (Author) Other; Battle, A (Author) Other; Mostafavi, S (Author) Other; Mele, M (Author) Other; Reverter, F (Author) Other; Goldmann, J (Author) Other; Koller, D (Author) Other; Gamazon, ER (Author) Other; Im, HK (Author) Other; Konkashbaev, A (Author) Other; Nicolae, DL (Author) Other; Cox, NJ (Author) Other; Flutre, T (Author) Other; Wen, X (Author) Other; Stephens, M (Author) Other; Pritchard, JK (Author) Other; Tu, Z (Author) Other; Zhang, B (Author) Other; Huang, T (Author) Other; Long, Q (Author) Other; Lin, L (Author) Other; Yang, J (Author) Other; Zhu, J (Author) Other; Liu, J (Author) Other; Brown, A (Author) Other; Mestichelli, B (Author) Other; Tidwell, D (Author) Other; Lo, E (Author) Other; Salvatore, M (Author) Other; Shad, S (Author) Other; Thomas, JA (Author) Other; Lonsdale, JT (Author) Other; Choi, RC (Author) Other; Karasik, E (Author) Other; Ramsey, K (Author) Other; Moser, MT (Author) Other; Foster, BA (Author) Other; Gillard, BM (Author) Other; Syron, J (Author) Other; Fleming, J (Author) Other; Magazine, H (Author) Other; Hasz, R (Author) Other; Walters, GD (Author) Other; Bridge, JP (Author) Other; Miklos, M (Author) Other; Sullivan, S (Author) Other; Barker, LK (Author) Other; Traino, H (Author) Other; Mosavel, M (Author) Other; Siminoff, LA (Author) Other; Valley, DR (Author) Other; Rohrer, DC (Author) Other; Jewel, S (Author) Other; Branton, P (Author) Other; Sobin, LH (Author) Other; Barcus, M (Author) Other; Qi, L (Author) Other; Hariharan, P (Author) Other; Wu, S (Author) Other; Tabor, D (Author) Other; Shive, C (Author) Other; Smith, AM (Author) Other; Buia, SA (Author) Other; Undale, AH (Author) Other; Robinson, KL (Author) Other; Roche, N (Author) Other; Valentino, KM (Author) Other; Britton, A (Author) Other; Burges, R (Author) Other; Bradbury, D (Author) Other; Hambright, KW (Author) Other; Seleski, J (Author) Other; Korzeniewski, GE (Author) Other; Erickson, K (Author) Other; Marcus, Y (Author) Other; Tejada, J (Author) Other; Taherian, M (Author) Other; Lu, C (Author) Other; Robles, BE (Author) Other; Basile, M (Author) Other; Mash, DC (Author) Other; Volpi, S (Author) Other; Struewing, JP (Author) Other; Temple, GF (Author) Other; Boyer, J (Author) Other; Colantuoni, D (Author) Other; Little, R (Author) Other; Koester, S (Author) Other; Carithers, LJ (Author) Other; Moore, HM (Author) Other; Guan, P (Author) Other; Compton, C (Author) Other; Sawyer, SJ (Author) Other; Demchok, JP (Author) Other; Vaught, JB (Author) Other; Rabiner, CA (Author) Other; Lockhart, NC (Author) Other; Friedlander, MR (Author) Other; 't Hoen, PAC (Author) Other; Monlong, J (Author) Other; Gonzalez-Porta, M (Author) Other; Kurbatova, N (Author) Other; Griebel, T (Author) Other; Barann, M (Author) Other; Wieland, T (Author) Other; Greger, L (Author) Other; van Iterson, M (Author) Other; Almlof, 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; 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; Flicek, P (Author) Other; Strom, TM (Author) Other; Lehrach, H (Author) Other; Schreiber, S (Author) Other; Sudbrak, R (Author) Other; Carracedo, A (Author) Other; Antonarakis, SE (Author) Other; Hasler, R (Author) Other; Syvanen, A (Author) Other; van Ommen, G (Author) Other; Brazma, A (Author) Other; Meitinger, T (Author) Other; Rosenstiel, P (Author) Other; Gut, IG (Author) Other; Estivill, X (Author) Other; The GTEx Consortium, (Author) Other; The Geuvadis Consortium, (Author) Other

Journal

Title: Science

Vol. 348

Pages: 666-669

ISSN: 0036-8075

Publisher: American Association for the Advancement of Science

Indexing

Scopus - 198 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-00Q-55C

DOI: 10.1126/science.1261877

Abstract (EN): Accurate prediction of the functional effect of genetic variation is critical for clinical genome interpretation.We systematically characterized the transcriptome effects of protein-truncating variants, a class of variants expected to have profound effects on gene function, using data from the Genotype-Tissue Expression (GTEx) and Geuvadis projects. We quantitated tissue-specific and positional effects on nonsense-mediated transcript decay and present an improved predictive model for this decay. We directly measured the effect of variants both proximal and distal to splice junctions. Furthermore, we found that robustness to heterozygous gene inactivation is not due to dosage compensation. Our results illustrate the value of transcriptome data in the functional interpretation of genetic variants.

Language: English

Type (Professor's evaluation): Scientific