Nature Communications (May 2020)
Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals
- Nicola Whiffin,
- Konrad J. Karczewski,
- Xiaolei Zhang,
- Sonia Chothani,
- Miriam J. Smith,
- D. Gareth Evans,
- Angharad M. Roberts,
- Nicholas M. Quaife,
- Sebastian Schafer,
- Owen Rackham,
- Jessica Alföldi,
- Anne H. O’Donnell-Luria,
- Laurent C. Francioli,
- Genome Aggregation Database Production Team,
- Genome Aggregation Database Consortium,
- Stuart A. Cook,
- Paul J. R. Barton,
- Daniel G. MacArthur,
- James S. Ware
Affiliations
- Nicola Whiffin
- National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London
- Konrad J. Karczewski
- Medical and Population Genetics, Broad Institute of MIT and Harvard
- Xiaolei Zhang
- National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London
- Sonia Chothani
- Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Miriam J. Smith
- NW Genomic Laboratory Hub, Centre for Genomic Medicine, Division of Evolution and Genomic Science, St Mary’s Hospital, University of Manchester
- D. Gareth Evans
- NW Genomic Laboratory Hub, Centre for Genomic Medicine, Division of Evolution and Genomic Science, St Mary’s Hospital, University of Manchester
- Angharad M. Roberts
- National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London
- Nicholas M. Quaife
- National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London
- Sebastian Schafer
- Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Owen Rackham
- Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Jessica Alföldi
- Medical and Population Genetics, Broad Institute of MIT and Harvard
- Anne H. O’Donnell-Luria
- Medical and Population Genetics, Broad Institute of MIT and Harvard
- Laurent C. Francioli
- Medical and Population Genetics, Broad Institute of MIT and Harvard
- Genome Aggregation Database Production Team
- Genome Aggregation Database Consortium
- Stuart A. Cook
- National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London
- Paul J. R. Barton
- National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London
- Daniel G. MacArthur
- Medical and Population Genetics, Broad Institute of MIT and Harvard
- James S. Ware
- National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London
- DOI
- https://doi.org/10.1038/s41467-019-10717-9
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 12
Abstract
Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.
