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Mapping of the Gene Network That Regulates Glycan Clock of Aging | Aging-US



January 3, 2024

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  • Aging-US published this research paper in Volume 15, Issue 24, entitled, “Mapping of the gene network that regulates glycan clock of ageing" by researchers from Genos Glycoscience Research Laboratory, Zagreb, Croatia; Department of Biology, Division of Molecular Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia; Laboratory of Theoretical and Applied Functional Genomics, Novosibirsk State University, Novosibirsk, Russia; MSU Institute for Artificial Intelligence, Lomonosov Moscow State University, Moscow, Russia; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK; Institute of Genomics, University of Tartu, Tartu, Estonia; Department of Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Pattern Recognition and Bioinformatics, Delft University of Technology, Delft, The Netherlands; Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München –Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Munich, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK; NIHR Biomedical Research Centre at Guy’s and St Thomas’ Foundation Trust, London, UK; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia; Department of Biotechnology, University of Rijeka, Rijeka, Croatia; Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; SciLifeLab, Division of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; University of Split School of Medicine, Split, Croatia; Algebra University College, Zagreb, Croatia; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia. DOI - Corresponding authors - Azra Frkatović-Hodžić -, and Gordan Lauc - Abstract Glycans are an essential structural component of immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a trait which was shown to be associated with ageing. We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Upregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system. Please visit our website at​​ and connect with us: SoundCloud - Facebook - X - Instagram - YouTube - LinkedIn - Pinterest - MEDIA@IMPACTJOURNALS.COM

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