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High-throughput functional dissection of noncoding SNPs with biased allelic enhancer activity for insulin resistance-relevant phenotypes
Affiliation:1. Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China;2. Department of Orthopedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China;3. Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China;4. Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN 46202, USA;5. Department of Ophthalmology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710000, China;1. Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany;2. Division of Nephrology, Endocrinology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany;3. Medical Genetics, Vall d''Hebron, Barcelona, Spain;4. Translational and Clinical Research Institute, Newcastle University, Central Parkway, NE1 3BZ Newcastle, UK;5. Division of Genomic Diagnostics at Children’s Hospital of Philadelphia, Philadelphia, PA, USA;6. Roberts Individualized Medical Genetics Center, Children''s Hospital of Philadelphia, Philadelphia, PA, USA;7. Institute of Human Genetics, Klinikum rechts der Isar, Technical University Munich, School of Medicine, Munich, Germany;8. Department of Nephrology, Klinikum rechts der Isar, Technical University Munich, School of Medicine, Munich, Germany;9. Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany;10. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany;11. Department of Pediatrics, University of Montreal, Montreal, QC, Canada;12. Hasso-Plattner-Institute, University of Potsdam, Potsdam, Germany;13. Hasso Plattner Institute for Digital Health at Mount Sinai School of Medicine, New York City, NY, USA;14. Institute for Molecular Medicine Finland: FIMM, University of Helsinki, Helsinki, Finland;15. Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany;16. Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland;17. Sheffield Children’s NHS Foundation Trust, Sheffield, UK;18. Unité neurovasculaire et troubles cognitifs, University of Poitiers, Poitiers, France;19. Equipe GAD, UMR1231 Inserm, Université de Bourgogne Franche Comté, Dijon, France;20. UF de Génétique Clinique Département de Génétique, CHU Paris - Hôpital Robert Debré, Paris, France;21. North East and Yorkshire Genomic Laboratory Hub, Central Laboratory, St. James’s University Hospital, Leeds, UK;22. Service de Pédiatrie, Centre Hospitalier Territorial, Nouvelle Calédonie, France;23. Service de Génétique Médicale, Centre de Référence Anomalies du Développement et Syndrome Malformatifs, CHU de Bordeaux, France;24. INSERM U1211, Maladies Rares: Génétique et Métabolisme (MRGM), Université de Bordeaux, Bordeaux, France;25. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA;26. Seattle Children ́s Hospital, Seattle, WA, USA;27. Berlin Institute of Health at Charité, Universitätsmedizin Berlin, Center of Functional Genomics, Berlin, Germany;28. The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Road, NE7 7DN Newcastle, UK;29. NIHR Newcastle Biomedical Research Centre, NE4 5PL Newcastle, UK;1. Pacific Northwest Research Institute, Seattle, WA, USA;2. Department of Applied Mathematics, University of Washington, Seattle, WA, USA;3. Center for Genetic Medicine Research, Children’s National Research Institute, Children’s National Hospital, Washington, DC, USA;4. Department of Genomics and Precision Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA;5. Department of Neurology, Division of Neurogenetics and Neurodevelopmental Disabilities, Children’s National Hospital, Washington, DC, USA;6. Center for Neuroscience Research, Children’s National Research Institute, Children’s National Hospital, Washington, DC, USA;1. The Dalglish Family 22q Clinic for Adults, and Department of Psychiatry, University Health Network, Toronto, ON, Canada;2. Toronto General Research Institute and Division of Cardiology, Department of Medicine, University Health Network, Toronto, ON, Canada;3. Clinical Genetics Research Program and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada;4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada;5. 22q and You Center, Clinical Genetics Center, and Section of Genetic Counseling, Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA;6. Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA;7. Department of Human Biology and Medical Genetics, Sapienza University, Rome, Italy;8. Advisium, ’s Heeren Loo Zorggroep, Amersfoort, the Netherlands;9. Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands;10. Department of Pediatric Rheumatology and Immunology, Queen Silvia Children’s Hospital, SahlgrenskaUniversity Hospital, Gothenburg, Sweden;11. Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;12. Genetics & Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada;13. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada;1. Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;2. Texas Children’s Hospital, Houston, TX, USA;3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;4. School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China;5. Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;6. Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;7. Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA;8. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA;9. Genetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel;10. Boys Town National Research Hospital, Boys Town, NE, USA;11. Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians University Munich, Munich, Germany;12. German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany;13. Department of Radiology, Baylor College of Medicine, Houston, TX, USA;14. E.B. Singleton Department of Pediatric Radiology, Texas Children’s Hospital, Houston, TX, USA;15. Autism & Developmental Medicine Institute, Geisinger, Danville, PA, USA;16. Department of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA;17. Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA;18. Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA;19. Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA;20. Division of Clinical Genetics, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA;21. Paediatric Radiology Department, AP-HP, Hôpital Necker Enfants Malades, Université Paris Cité, Institut Imagine INSERM U1163, 75015 Paris, France;22. Service de Médecine Génomique des Maladies Rares – APHP, Hôpital Necker Enfants Malades, Université de Paris, Paris, France;23. Genomic Medicine Center, Children’s Mercy Hospital, Kansas City, MO, USA;24. University of Missouri Kansas City School of Medicine, Kansas City, MO, USA;25. Department of Neurology, UT Health Science Center at Houston, McGovern Medical School, Houston, TX, USA;26. Neuroscience Department, Meyer Children’s Hospital IRCCS, Florence, Italy;27. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;28. Lifetime Neurodevelopmental Care, San Francisco, CA, USA;29. North East Thames Regional Genetic Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK;30. Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;31. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;32. Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;33. GeneDx, Gaithersburg, MD, USA;34. Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l’Interrégion Est, Fédération Hospitalo-Universitaire Médecine TRANSLationnelle et Anomalies du Développement, Centre Hospitalier Universitaire Dijon, Equipe Genetics of Developmental Anomalies-INSERM UMR 1231, Dijon, France;35. Functional Unit for Diagnostic Innovation in Rare Diseases, FHU-TRANSLAD, Dijon Bourgogne University Hospital, Dijon, France;36. INSERM UMR1231 GAD “Génétique des Anomalies du Développement,” FHU-TRANSLAD, University of Burgundy, Dijon, France;37. Department of Genetics and Reference Center for Development Disorders and Intellectual Disabilities, Dijon Bourgogne University Hospital, Dijon, France;38. Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany;39. Institute of Mother and Child, Kasprzaka 17a, 02-211 Warsaw, Poland;40. Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road L103, Portland, OR, USA;41. Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait;42. University of Florence, Florence, Italy;43. Chair of Experimental Genetics, TUM School of Life Sciences, Technische Universität München, Alte Akademie 8, 85354 Freising, Germany;44. Technische Universität München, Freising-Weihenstephan, Germany;45. Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China;46. Kunming Institute of Zoology Chinese Academy of Sciences, the Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Hong Kong SAR, China;47. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;1. Institute of Human Genetics, University of Leipzig Medical Center, 04103 Leipzig, Germany;2. Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan;3. Analytic and Translational Genetics Unit, Department of Medicine, Boston, MA, USA;4. Massachusetts General Hospital, Boston, MA 02114, USA;5. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA;6. Division of General Biochemistry, Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, 04103 Leipzig, Germany;7. Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;8. Pediatric Research Center, University Hospital for Children and Adolescents, Leipzig University, 04103 Leipzig, Germany;9. CeGaT GmbH, 72076 Tuebingen, Germany;10. Hertie-Institute for Clinical Brain Research, 72070 Tubingen, Germany;11. Cologne Center for Genomics, University of Cologne, 50937 Cologne, Germany;12. Center for Rare Diseases, University of Leipzig Medical Center, 04103 Leipzig, Germany;13. Hasso-Plattner-Institut for Digital Engineering, University of Potsdam, Potsdam, Germany;14. Hasso Plattner Institute at Mount Sinai, Mount Sinai School of Medicine, New York, NY, USA;15. Institute for Molecular Medicine Finland: FIMM, University of Helsinki, Helsinki, Finland;1. Neuroscience Department, Meyer Children’s Hospital IRCCS, Florence, Italy;2. University of Florence, Florence, Italy;3. Department of Neuroscience, Psychology, Drug Research and Child Health (NeuroFarBa), Section of Pharmacology and Toxicology, University of Florence, Florence, Italy;4. Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK;5. Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK;6. Department of Neurology and Institute of Human Genetics and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA;7. National Enterprise for NanoScience and NanoTechnology (NEST), Istituto Nanoscienze, Consiglio Nazionale delle Ricerche (CNR) and Scuola Normale Superiore Pisa, Pisa, Italy;8. Division of Metabolic Disorders, Children’s Hospital of Orange County (CHOC), Orange, CA, USA;9. Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia;10. Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands;11. Institute of Human Genetics, School of Medicine, Technical University Munich, Munich, Germany;12. Department of Pediatric Neurology and Developmental Medicine, Dr. v. Hauner Children’s Hospital, LMU - University of Munich, München, Germany;13. William Harvey Research Institute, Queen Mary University of London, London, UK;14. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA;15. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004 Japan;16. Department of Neurology, The Children’s Hospital at Westmead and the Children’s Hospital at Westmead Clinical School, University of Sydney, Westmead NSW, Australia;17. Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France;18. Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Département de Génétique, DMU BioGeM, Paris, France;19. Northern Genetics Service, Newcastle upon Tyne hospitals NHS Foundation Trust, Newcastle, UK;20. New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW 2031, Australia;21. Neuroscience Research Australia, Sydney, NSW 2031, Australia;22. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy;23. Institute for Transition, Rehabilitation and Palliation, Paracelsus Medical University, Salzburg, Austria;24. Department of Precision Medicine, University “Luigi Vanvitelli,” Naples, Italy;25. Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy;26. Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Niigata 950-2085, Japan;27. Department for Child Health and Human Development, Saitama Children’s Medical Center, Saitama 330-8777, Japan;28. Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan;29. School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan;30. Brain Research Institute, Niigata University, Niigata 951-8585, Japan;31. Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands;32. Centre de référence Maladies Rares “Déficience intellectuelle de cause rare,” Sorbonne Université, Paris, France;33. Département de Neuropédiatrie, Hôpital Armand Trousseau, APHP, Sorbonne Université, Paris, France;34. Department of Neurosciences, Queensland Children’s Hospital, Brisbane QLD, Australia;35. Centre for Advanced Imaging, University of Queensland, St Lucia QLD, Australia;36. Department of Pediatrics, Showa University School of Medicine, Tokyo 142-8666, Japan;37. Istituto Neuroscienze CNR, Padova, Italy
Abstract:
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  • Keywords:insulin resistance  STARR-seq  GWAS  noncoding SNPs  biased allelic enhancer activity effect  rs952227  genetic regulatory mechanisms
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