Publisher Correction: Identification and characterization of two functional variants in the human longevity gene FOXO3
| Autor: | Susanne Sebens, Marlene Jentzsch, Kaare Christensen, Michael Nothnagel, Liljana Gentschew, Sandra May, Stefan Schreiber, Hélène Blanché, Pilar Galan, Alexander Arlt, Amke Caliebe, Guillermo G. Torres, Abdou ElSharawy, Lene Christiansen, Friederike Flachsbart, Gerald Rimbach, Wolfgang Lieb, Anne Luzius, Carolin Knecht, Robert Häsler, Marianne Nygaard, Nandini Badarinarayan, Andre Franke, Jean-François Deleuze, Céline Derbois, Kathrin Pallauf, Claudia Geismann, Michael Forster, Andreas Till, Almut Nebel, Dmitriy Drichel, Janina Dose, Philip Rosenstiel, Ben Krause-Kyora |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine CCCTC-Binding Factor Serum Response Factor Published Erratum Computer science Science Longevity MEDLINE General Physics and Astronomy Computational biology Polymorphism Single Nucleotide White People General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Humans Computer Simulation RNA Messenger Insulin-Like Growth Factor I lcsh:Science Gene Alleles Aged Aged 80 and over Multidisciplinary Forkhead Box Protein O3 Age Factors General Chemistry Middle Aged Publisher Correction Introns Spelling 030104 developmental biology Haplotypes Human longevity lcsh:Q Female Identification (biology) |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-2 (2018) Flachsbart, F, Dose, J, Gentschew, L, Geismann, C, Caliebe, A, Knecht, C, Nygaard, M, Badarinarayan, N, ElSharawy, A, May, S, Luzius, A, Torres, G G, Jentzsch, M, Forster, M, Häsler, R, Pallauf, K, Lieb, W, Derbois, C, Galan, P, Drichel, D, Arlt, A, Till, A, Krause-Kyora, B, Rimbach, G, Blanché, H, Deleuze, J-F, Christiansen, L, Christensen, K, Nothnagel, M, Rosenstiel, P, Schreiber, S, Franke, A, Sebens, S & Nebel, A 2018, ' Publisher Correction : Identification and characterization of two functional variants in the human longevity gene FOXO3 ', Nature Communications, vol. 9, 320 . https://doi.org/10.1038/s41467-018-02842-8 |
| ISSN: | 2041-1723 |
| Popis: | FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs. Specifically, in luciferase reporter assays, the longevity alleles of both variants show considerable enhancer activities that are reversed by IGF-1 treatment. An eQTL database search reveals that the alleles are also associated with higher FOXO3 mRNA expression in various human tissues, which is in line with observations in long-lived model organisms. In summary, we present experimental evidence for a functional link between common intronic variants in FOXO3 and human longevity. |
| Databáze: | OpenAIRE |
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