التفاصيل البيبلوغرافية
| العنوان: |
Quantifying prion disease penetrance using large population control cohorts |
| المؤلفون: |
Minikel, Eric Vallabh, Vallabh, Sonia M., Lek, Monkol, Estrada, Karol, Samocha, Kaitlin E., Sathirapongsasuti, J. Fah, McLean, Cory Y., Tung, Joyce Y., Yu, Linda P. C., Gambetti, Pierluigi, Blevins, Janis, Zhang, Shulin, Cohen, Yvonne, Chen, Wei, Yamada, Masahito, Hamaguchi, Tsuyoshi, Sanjo, Nobuo, Mizusawa, Hidehiro, Nakamura, Yosikazu, Kitamoto, Tetsuyuki, Collins, Steven J., Boyd, Alison, Will, Robert G., Knight, Richard, Ponto, Claudia, Zerr, Inga, Kraus, Theo F.J., Eigenbrod, Sabina, Giese, Armin, Calero, Miguel, De Pedro-Cuesta, Jesús, Haïk, Stéphane, Laplanche, Jean-Louis, Bouaziz-Amar, Elodie, Brandel, Jean-Philippe, Capellari, Sabina, Parchi, Piero, Poleggi, Anna, Ladogana, Anna, O'Donnell-Luria, Anne H., Karczewski, Konrad J., Marshall, Jamie L., Boehnke, Michael, Laakso, Markku, Mohlke, Karen L., Kähler, Anna, Chambert, Kimberly, McCarroll, Steven, Sullivan, Patrick F., Hultman, Christina M., Purcell, Shaun M., Sklar, Pamela, Van Der Lee, Sven J., Rozemuller, Annemieke, Jansen, Casper, Hofman, Albert, Kraaij, Robert, Van Rooij, Jeroen G. J., Ikram, M. Arfan, Uitterlinden, André G., Van Duijn, Cornelia M., Daly, Mark J., MacArthur, Daniel G. |
| المصدر: |
Science Translational Medicine, 8(322) |
| سنة النشر: |
2016 |
| المجموعة: |
Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: |
Humans, Cell Biology, Exome Aggregation Consor, Prions, UNCOMMON POLYMORPHISM RATHER, Genetic Predisposition to Disease, Penetrance, Cohort Studies, Science & Technology, Mutation, Medicine, FATAL FAMILIAL INSOMNIA, Research & Experimental, POINT MUTATION, Risk Factors, Prion Diseases, PROTEIN GENE MUTATION, Research & Experimental Medicine, TRANSGENIC MOUSE MODEL, PRNP GENE, STRAUSSLER-SCHEINKER-DISEASE, AMYLOID PRECURSOR GENE, Life Sciences & Biomedicine, Case-Control Studies, R208H MUTATION, CREUTZFELDT-JAKOB-DISEASE |
| الوصف: |
More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance - the probability that a carrier of the purported disease-causing genotype will indeed develop the disease - is generally unknown. Here we assess the impact of variants in the prion protein gene (PRNP) on the risk of prion disease by analyzing 16,025 prion disease cases, 60,706 population control exomes, and 531,575 individuals genotyped by 23andMe, Inc. We show that missense variants in PRNP previously reported to be pathogenic are at least 30× more common in the population than expected based on genetic prion disease prevalence. While some of this excess can be attributed to benign variants falsely assigned as pathogenic, other variants have genuine effects on disease susceptibility but confer lifetime risks ranging from <0.1% to ~100%. We also show that truncating variants in PRNP have position-dependent effects, with true loss-of-function alleles found in healthy older individuals, supporting the safety of therapeutic suppression of prion protein expression. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
https://doi.org/10.17615/m8r0-g416Test; https://cdr.lib.unc.edu/downloads/2v23w070k?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/2v23w070kTest |
| DOI: |
10.17615/m8r0-g416 |
| الإتاحة: |
https://doi.org/10.17615/m8r0-g416Test
https://cdr.lib.unc.edu/downloads/2v23w070k?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/2v23w070kTest |
| حقوق: |
http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: |
edsbas.5BDFED10 |
| قاعدة البيانات: |
BASE |
