Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction
| Autor: | Vanja Sisirak, Lai-Shan Tam, Yueyang Wang, Wenlei Peng, Rossa W.K. Chiu, Lee Serpas, Alberto Magnasco, Pik Ki Lau, K.C. Allen Chan, Y.M. Dennis Lo, Wing-Shan Lee, Elisa Buti, Rebecca W.Y. Chan, Meng Ni, Diana S.C. Han, Priscilla Wong, Peiyong Jiang, Boris Reizis, Nora AlMutairi, Lydia Ho-Pui Tam, Ali Rashidfarrokhi, Alice S.H. Cheng, Patty P.P. Tse, Linda T. Hiraki, Stefano Volpi |
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| Přispěvatelé: | Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, Clinica Pediatrica e Reumatologia, Centro per le malattie Autoinfiammatorie e Immunodeficienze, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genova, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Università degli Studi di Genova, 16132 Genova, Division of Rheumatology, The Hospital for Sick Children, Toronto, ON M5G 1X5, Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, Division of Nephrology, Dialysis and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Giannina Gaslini, 16147 Genova, Nefrologia e Dialisi, Azienda Ospedaliero Universitaria Meyer, 50139 Firenze, Immunology from Concept and Experiments to Translation (ImmunoConcept), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Sabah Hospital, Jaber Al Ahmad Al Jaber Al Sabah Hospital |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] Cell Gene mutation Transgenic Substrate Specificity Transduction (genetics) chemistry.chemical_compound Mice 0302 clinical medicine systemic lupus erythematosus Transduction Genetic Lupus Erythematosus Systemic cfDNA Genetics (clinical) biology Chemistry Dependovirus 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis DNA fragmentation Genetic Vectors Mice Transgenic autoimmune disease DNA Fragmentation Article 03 medical and health sciences Transduction Genetic Genetics medicine Extracellular biomarkers circulating DNA liquid biopsy Animals Case-Control Studies DNA Disease Models Animal Endodeoxyribonucleases Genetic Therapy Humans Mutation Gene Nuclease Lupus Erythematosus Animal Systemic Molecular biology 030104 developmental biology Disease Models biology.protein |
| Zdroj: | American Journal of Human Genetics American Journal of Human Genetics, Elsevier (Cell Press), 2020, 107, pp.882-894. ⟨10.1016/j.ajhg.2020.09.006⟩ |
| ISSN: | 0002-9297 1537-6605 |
| DOI: | 10.1016/j.ajhg.2020.09.006⟩ |
| Popis: | International audience; Plasma DNA fragmentomics is an emerging area in cell-free DNA diagnostics and research. In murine models, it has been shown that the extracellular DNase, DNASE1L3, plays a role in the fragmentation of plasma DNA. In humans, DNASE1L3 deficiency causes familial monogenic systemic lupus erythematosus with childhood onset and anti-dsDNA reactivity. In this study, we found that human patients with DNASE1L3 disease-associated gene variations showed aberrations in size and a reduction of a ''CC'' end motif of plasma DNA. Furthermore, we demonstrated that DNA from DNASE1L3-digested cell nuclei showed a median length of 153 bp with CC motif frequencies resembling plasma DNA from healthy individuals. Adeno-associated virus-based transduction of Dnase1l3 into Dnase1l3-deficient mice restored the end motif profiles to those seen in the plasma DNA of wild-type mice. Our findings demonstrate that DNASE1L3 is an important player in the fragmentation of plasma DNA, which appears to act in a cell-extrinsic manner to regulate plasma DNA size and motif frequency. |
| Databáze: | OpenAIRE |
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