Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques

Martina Rauner et al, 30 November 2021 

Martina Rauner, ^1,2Ines Foessl, ³Melissa M. Formosa, ^4,5Erika Kague, ⁶Vid Prijatelj, ^7,8,9Nerea Alonso Lopez, ¹⁰Bodhisattwa Banerjee, ¹¹Dylan Bergen, ^6,12Björn Busse, ¹³Ângelo Calado, ¹⁴Eleni Douni, ^15,16Yankel Gabet, ¹⁷Natalia García Giralt, ¹⁸Daniel Grinberg, ¹⁹Nika M. Lovsin, ²⁰Xavier Nogues Solan, ¹⁸Barbara Ostanek, ²⁰Nathan J. Pavlos, ²¹Fernando Rivadeneira, ²²Ivan Soldatovic, ²³Jeroen van de Peppel, ⁸Bram van der Eerden, ⁸Wim van Hul, ²⁴Susanna Balcells, ¹⁹Janja Marc, ²⁰Sjur Reppe, ^25,26,27Kent Søe ^28,29,30and David Karasik^31,32*‡

• ¹Department of Medicine III, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
• ²University Hospital Carl Gustav Carus, Dresden, Germany
• ³Department of Internal Medicine, Division of Endocrinology and Diabetology, Endocrine Lab Platform, Medical University of Graz, Graz, Austria
• ⁴Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta
• ⁵Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta
• ⁶School of Physiology, Pharmacology, and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, United Kingdom
• ⁷Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
• ⁸Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
• ⁹The Generation R Study, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
• ¹⁰Rheumatology and Bone Disease Unit, CGEM, Institute of Genetics and Cancer (IGC), Edinburgh, United Kingdom
• ¹¹Musculoskeletal Genetics Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
• ¹²Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, United Kingdom
• ¹³Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
• ¹⁴Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisbon, Portugal
• ¹⁵Department of Biotechnology, Agricultural University of Athens, Athens, Greece
• ¹⁶Institute for Bioinnovation, B.S.R.C. “Alexander Fleming”, Vari, Greece
• ¹⁷Department of Anatomy & Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
• ¹⁸Musculoskeletal Research Group, IMIM (Hospital del Mar Medical Research Institute), Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain
• ¹⁹Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
• ²⁰Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
• ²¹Bone Biology & Disease Laboratory, School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia
• ²²Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands
• ²³Institute of Medical Statistics and Informatic, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
• ²⁴Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
• ²⁵Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
• ²⁶Department of Plastic and Reconstructive Surgery, Oslo University Hospital, Oslo, Norway
• ²⁷Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
• ²⁸Clinical Cell Biology, Department of Pathology, Odense University Hospital, Odense, Denmark
• ²⁹Department of Clinical Research, University of Southern Denmark, Odense, Denmark
• ³⁰Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
• ³¹Azrieli Faculty of Medicine, Bar-Ilan University, Ramat Gan, Israel
• ³²Marcus Research Institute, Hebrew SeniorLife, Boston, MA, United States

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.

Read the full paper here.