Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes
Abstract Long-read sequencing can often overcome the deficiencies in routine microarray or short-read technologies in detecting complex genomic rearrangements. Here we used Pacific Biosciences circular consensus sequencing to resolve complex rearrangements in two patients with rare genetic anomalies...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-024-00454-4 |
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| author | Iftekhar A. Showpnil Maria E. Hernandez Gonzalez Swetha Ramadesikan Mohammad Marhabaie Allison Daley Leeran Dublin-Ryan Matthew T. Pastore Umamaheswaran Gurusamy Jesse M. Hunter Brandon S. Stone Dennis W. Bartholomew Kandamurugu Manickam Anthony R. Miller Richard K. Wilson Rolf W. Stottmann Daniel C. Koboldt |
| author_facet | Iftekhar A. Showpnil Maria E. Hernandez Gonzalez Swetha Ramadesikan Mohammad Marhabaie Allison Daley Leeran Dublin-Ryan Matthew T. Pastore Umamaheswaran Gurusamy Jesse M. Hunter Brandon S. Stone Dennis W. Bartholomew Kandamurugu Manickam Anthony R. Miller Richard K. Wilson Rolf W. Stottmann Daniel C. Koboldt |
| author_sort | Iftekhar A. Showpnil |
| collection | DOAJ |
| description | Abstract Long-read sequencing can often overcome the deficiencies in routine microarray or short-read technologies in detecting complex genomic rearrangements. Here we used Pacific Biosciences circular consensus sequencing to resolve complex rearrangements in two patients with rare genetic anomalies. Copy number variants (CNVs) identified by clinical microarray —chr8p deletion and chr8q duplication in patient 1, and interstitial deletions of chr18q in patient 2—were suggestive of underlying rearrangements. Long-read genome sequencing not only confirmed these CNVs but also revealed their genomic structures. In patient 1, we resolved a novel recombinant chromosome 8 (Rec8)-like rearrangement with a 3.43 Mb chr8q terminal duplication that was linked to a 7.25–8.21 Mb chr8p terminal deletion. In patient 2, we uncovered a novel complex rearrangement involving a 1.17 Mb rearranged segment and four interstitial deletions ranging from 9 bp to 12.39 Mb. Our results underscore the diversity of clinically relevant structural rearrangements and the power of long-read sequencing in unraveling their nuanced architectures. |
| format | Article |
| id | doaj-art-a4f7cdcd1f8b40b4abac22ac18b0dace |
| institution | OA Journals |
| issn | 2056-7944 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj-art-a4f7cdcd1f8b40b4abac22ac18b0dace2025-08-20T01:57:16ZengNature Portfolionpj Genomic Medicine2056-79442024-12-019111210.1038/s41525-024-00454-4Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromesIftekhar A. Showpnil0Maria E. Hernandez Gonzalez1Swetha Ramadesikan2Mohammad Marhabaie3Allison Daley4Leeran Dublin-Ryan5Matthew T. Pastore6Umamaheswaran Gurusamy7Jesse M. Hunter8Brandon S. Stone9Dennis W. Bartholomew10Kandamurugu Manickam11Anthony R. Miller12Richard K. Wilson13Rolf W. Stottmann14Daniel C. Koboldt15The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalDivision of Genetic & Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalDivision of Genetic & Genomic Medicine, Nationwide Children’s HospitalDivision of Genetic & Genomic Medicine, Nationwide Children’s HospitalDivision of Genetic & Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s HospitalAbstract Long-read sequencing can often overcome the deficiencies in routine microarray or short-read technologies in detecting complex genomic rearrangements. Here we used Pacific Biosciences circular consensus sequencing to resolve complex rearrangements in two patients with rare genetic anomalies. Copy number variants (CNVs) identified by clinical microarray —chr8p deletion and chr8q duplication in patient 1, and interstitial deletions of chr18q in patient 2—were suggestive of underlying rearrangements. Long-read genome sequencing not only confirmed these CNVs but also revealed their genomic structures. In patient 1, we resolved a novel recombinant chromosome 8 (Rec8)-like rearrangement with a 3.43 Mb chr8q terminal duplication that was linked to a 7.25–8.21 Mb chr8p terminal deletion. In patient 2, we uncovered a novel complex rearrangement involving a 1.17 Mb rearranged segment and four interstitial deletions ranging from 9 bp to 12.39 Mb. Our results underscore the diversity of clinically relevant structural rearrangements and the power of long-read sequencing in unraveling their nuanced architectures.https://doi.org/10.1038/s41525-024-00454-4 |
| spellingShingle | Iftekhar A. Showpnil Maria E. Hernandez Gonzalez Swetha Ramadesikan Mohammad Marhabaie Allison Daley Leeran Dublin-Ryan Matthew T. Pastore Umamaheswaran Gurusamy Jesse M. Hunter Brandon S. Stone Dennis W. Bartholomew Kandamurugu Manickam Anthony R. Miller Richard K. Wilson Rolf W. Stottmann Daniel C. Koboldt Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes npj Genomic Medicine |
| title | Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes |
| title_full | Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes |
| title_fullStr | Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes |
| title_full_unstemmed | Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes |
| title_short | Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes |
| title_sort | long read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes |
| url | https://doi.org/10.1038/s41525-024-00454-4 |
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