Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques
| Autor: | Rauner, Martina, Foessl, Ines, Formosa, Melissa M., Kague, Erika, Prijatelj, Vid, Alonso-Lopez, Nerea, Banerjee, Bodhisattwa, Bergen, Dylan, Busse, Björn, Calado, Ângelo, Douni, Eleni, Gabet, Yankel, Garcia Giralt, Natàlia, Grinberg Vaisman, Daniel Raúl, Lovsin, Nika M., Nogués Solán, Xavier, Ostanek, Barbara, Pavlos, Nathan J., Rivadeneira, Fernando, Soldatovic, Ivan, van de Peppel, Jeroen, van der Eerden, Bram, van Hul, Wim, Balcells Comas, Susana, Marc, Janja, Reppe, Sjur, Soe, Kent, Karasik, David |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Multifactorial Inheritance
Quantitative Trait Loci Musculoskeletal system -- Diseases Review Validation Studies as Topic Animals Genetically Modified Endocrinology Regulació genètica Animals Humans Genetic Predisposition to Disease Musculoskeletal Diseases Data integration (Computer science) Bone Genetic regulation genome-wide association study data integration analysis animal models Gene regulation Animal models Systems Integration Phenotype Genomes -- Analysis Models Animal Human medicine Bone Diseases musculoskeletal disorders Malalties de l'aparell locomotor gene regulation musculoskeletal disease Enfermedades del aparato locomotor |
| Zdroj: | Rauner, M, Foessl, I, Formosa, M M, Kague, E, Prijatelj, V, Lopez, N A, Banerjee, B, Bergen, D, Busse, B, Calado, Â, Douni, E, Gabet, Y, Giralt, N G, Grinberg, D, Lovsin, N M, Solan, X N, Ostanek, B, Pavlos, N J, Rivadeneira, F, Soldatovic, I, van de Peppel, J, van der Eerden, B, van Hul, W, Balcells, S, Marc, J, Reppe, S, Søe, K & Karasik, D 2021, ' Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques ', Frontiers in Endocrinology, vol. 12, 731217, pp. 731217 . https://doi.org/10.3389/fendo.2021.731217 Frontiers in Endocrinology Rauner, M, Foessl, I, Formosa, M M, Kague, E, Prijatelj, V, Alonso Lopez, N, Banerjee, B, Bergen, D, Busse, B, Calado, Ã, Douni, E, Gabet, Y, Garcia Giralt, N, Grinberg, D, Lovsin, N M, Nogues Solan, X, Ostanek, B, Pavlos, N J, Rivadeneira, F, Soldatovic, I, van de Peppel, J, van der Eerden, B C J, Van Hul, W, Balcells, S, Marc, J, Reppe, S, Søe, K & Karasik, D 2021, ' Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques ', Frontiers in Endocrinology, vol. 12, 731217 . https://doi.org/10.3389/fendo.2021.731217 r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname Frontiers in endocrinology |
| ISSN: | 1664-2392 |
| Popis: | The availability of large human datasets for genome-wide association studies (GWAS) and the advancement of sequencing technologies have boosted the identification of genetic variants in complex and rare diseases in the skeletal field. Yet, interpreting results from human association studies remains a challenge. To bridge the gap between genetic association and causality, a systematic functional investigation is necessary. Multiple unknowns exist for putative causal genes, including cellular localization of the molecular function. Intermediate traits (“endophenotypes”), e.g. molecular quantitative trait loci (molQTLs), are needed to identify mechanisms of underlying associations. Furthermore, index variants often reside in non-coding regions of the genome, therefore challenging for interpretation. Knowledge of non-coding variance (e.g. ncRNAs), repetitive sequences, and regulatory interactions between enhancers and their target genes is central for understanding causal genes in skeletal conditions. Animal models with deep skeletal phenotyping and cell culture models have already facilitated fine mapping of some association signals, elucidated gene mechanisms, and revealed disease-relevant biology. However, to accelerate research towards bridging the current gap between association and causality in skeletal diseases, alternative in vivo platforms need to be used and developed in parallel with the current -omics and traditional in vivo resources. Therefore, we argue that as a field we need to establish resource-sharing standards to collectively address complex research questions. These standards will promote data integration from various -omics technologies and functional dissection of human complex traits. In this mission statement, we review the current available resources and as a group propose a consensus to facilitate resource sharing using existing and future resources. Such coordination efforts will maximize the acquisition of knowledge from different approaches and thus reduce redundancy and duplication of resources. These measures will help to understand the pathogenesis of osteoporosis and other skeletal diseases towards defining new and more efficient therapeutic targets. peer-reviewed |
| Databáze: | OpenAIRE |
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