Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19
Summary: Impressive global efforts have identified both rare and common gene variants associated with severe COVID-19 using sequencing technologies. However, these studies lack the sensitivity to accurately detect several classes of variants, especially large structural variants (SVs), which account...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422200030X |
| _version_ | 1819289198760296448 |
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| author | Nikhil Shri Sahajpal Chi-Yu Jill Lai Alex Hastie Ashis K. Mondal Siavash Raeisi Dehkordi Caspar I. van der Made Olivier Fedrigo Farooq Al-Ajli Sawan Jalnapurkar Marta Byrska-Bishop Rashmi Kanagal-Shamanna Brynn Levy Maximilian Schieck Thomas Illig Silviu-Alin Bacanu Janet S. Chou Adrienne G. Randolph Amyn M. Rojiani Michael C. Zody Catherine A. Brownstein Alan H. Beggs Vineet Bafna Erich D. Jarvis Alexander Hoischen Alka Chaubey Ravindra Kolhe |
| author_facet | Nikhil Shri Sahajpal Chi-Yu Jill Lai Alex Hastie Ashis K. Mondal Siavash Raeisi Dehkordi Caspar I. van der Made Olivier Fedrigo Farooq Al-Ajli Sawan Jalnapurkar Marta Byrska-Bishop Rashmi Kanagal-Shamanna Brynn Levy Maximilian Schieck Thomas Illig Silviu-Alin Bacanu Janet S. Chou Adrienne G. Randolph Amyn M. Rojiani Michael C. Zody Catherine A. Brownstein Alan H. Beggs Vineet Bafna Erich D. Jarvis Alexander Hoischen Alka Chaubey Ravindra Kolhe |
| author_sort | Nikhil Shri Sahajpal |
| collection | DOAJ |
| description | Summary: Impressive global efforts have identified both rare and common gene variants associated with severe COVID-19 using sequencing technologies. However, these studies lack the sensitivity to accurately detect several classes of variants, especially large structural variants (SVs), which account for a substantial proportion of genetic diversity including clinically relevant variation. We performed optical genome mapping on 52 severely ill COVID-19 patients to identify rare/unique SVs as decisive predisposition factors associated with COVID-19. We identified 7 SVs involving genes implicated in two key host-viral interaction pathways: innate immunity and inflammatory response, and viral replication and spread in nine patients, of which SVs in STK26 and DPP4 genes are the most intriguing candidates. This study is the first to systematically assess the potential role of SVs in the pathogenesis of COVID-19 severity and highlights the need to evaluate SVs along with sequencing variants to comprehensively associate genomic information with interindividual variability in COVID-19 phenotypes. |
| first_indexed | 2024-12-24T03:03:02Z |
| format | Article |
| id | doaj.art-6522ade0da724f48b8c81dc340d11287 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-24T03:03:02Z |
| publishDate | 2022-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-6522ade0da724f48b8c81dc340d112872022-12-21T17:18:09ZengElsevieriScience2589-00422022-02-01252103760Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19Nikhil Shri Sahajpal0Chi-Yu Jill Lai1Alex Hastie2Ashis K. Mondal3Siavash Raeisi Dehkordi4Caspar I. van der Made5Olivier Fedrigo6Farooq Al-Ajli7Sawan Jalnapurkar8Marta Byrska-Bishop9Rashmi Kanagal-Shamanna10Brynn Levy11Maximilian Schieck12Thomas Illig13Silviu-Alin Bacanu14Janet S. Chou15Adrienne G. Randolph16Amyn M. Rojiani17Michael C. Zody18Catherine A. Brownstein19Alan H. Beggs20Vineet Bafna21Erich D. Jarvis22Alexander Hoischen23Alka Chaubey24Ravindra Kolhe25Department of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USABionano Genomics, Inc., San Diego, CA 92121, USABionano Genomics, Inc., San Diego, CA 92121, USADepartment of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USADepartment of Computer Science and Engineering, University of California at San Diego, San Diego, CA 92093, USADepartment of Human Genetics, Radboud University Medical Center for Infectious Diseases (RCI), Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, and Radboud Expertise Center for Immunodeficiency and Autoinflammation, Radboud University Medical Center, 6525 Nijmegen, the NetherlandsVertebrate Genome Lab, The Rockefeller University, New York, NY 10065, USAVertebrate Genome Lab, The Rockefeller University, New York, NY 10065, USADepartment of Medicine, Medical College of Georgia, Augusta University, GA 30912, USANew York Genome Center, New York, NY 10013, USAHematopathology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USADepartment of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USADepartment of Human Genetics, Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover 30625, GermanyDepartment of Human Genetics, Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover 30625, Germany; Hannover Unified Biobank (HUB), Hannover 30625, GermanyDepartment of Psychiatry, Virginia Commonwealth University, Richmond, VA 23284, USADivision of Immunology, Boston Children's Hospital, Boston, MA 02115, USADepartment of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital, Boston, MA 02115, USA; Departments of Anesthesia and Pediatrics, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USANew York Genome Center, New York, NY 10013, USADivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Computer Science and Engineering, University of California at San Diego, San Diego, CA 92093, USAVertebrate Genome Lab, The Rockefeller University, New York, NY 10065, USA; Laboratory of Neurogenetics of Language, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USADepartment of Human Genetics, Radboud University Medical Center for Infectious Diseases (RCI), Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, and Radboud Expertise Center for Immunodeficiency and Autoinflammation, Radboud University Medical Center, 6525 Nijmegen, the NetherlandsDepartment of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USA; Bionano Genomics, Inc., San Diego, CA 92121, USADepartment of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USA; Corresponding authorSummary: Impressive global efforts have identified both rare and common gene variants associated with severe COVID-19 using sequencing technologies. However, these studies lack the sensitivity to accurately detect several classes of variants, especially large structural variants (SVs), which account for a substantial proportion of genetic diversity including clinically relevant variation. We performed optical genome mapping on 52 severely ill COVID-19 patients to identify rare/unique SVs as decisive predisposition factors associated with COVID-19. We identified 7 SVs involving genes implicated in two key host-viral interaction pathways: innate immunity and inflammatory response, and viral replication and spread in nine patients, of which SVs in STK26 and DPP4 genes are the most intriguing candidates. This study is the first to systematically assess the potential role of SVs in the pathogenesis of COVID-19 severity and highlights the need to evaluate SVs along with sequencing variants to comprehensively associate genomic information with interindividual variability in COVID-19 phenotypes.http://www.sciencedirect.com/science/article/pii/S258900422200030XGenetic sampleGenomicsVirology |
| spellingShingle | Nikhil Shri Sahajpal Chi-Yu Jill Lai Alex Hastie Ashis K. Mondal Siavash Raeisi Dehkordi Caspar I. van der Made Olivier Fedrigo Farooq Al-Ajli Sawan Jalnapurkar Marta Byrska-Bishop Rashmi Kanagal-Shamanna Brynn Levy Maximilian Schieck Thomas Illig Silviu-Alin Bacanu Janet S. Chou Adrienne G. Randolph Amyn M. Rojiani Michael C. Zody Catherine A. Brownstein Alan H. Beggs Vineet Bafna Erich D. Jarvis Alexander Hoischen Alka Chaubey Ravindra Kolhe Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19 iScience Genetic sample Genomics Virology |
| title | Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19 |
| title_full | Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19 |
| title_fullStr | Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19 |
| title_full_unstemmed | Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19 |
| title_short | Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19 |
| title_sort | optical genome mapping identifies rare structural variations as predisposition factors associated with severe covid 19 |
| topic | Genetic sample Genomics Virology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422200030X |
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