Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes.

Autor: Showpnil IA; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., E Hernandez Gonzalez M; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Ramadesikan S; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Marhabaie M; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Daley A; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Dublin-Ryan L; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Pastore MT; Division of Genetic & Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Gurusamy U; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Hunter JM; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Stone BS; Division of Genetic & Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Bartholomew DW; Division of Genetic & Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Manickam K; Division of Genetic & Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Miller AR; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Wilson RK; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Stottmann RW; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Koboldt DC; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA. Daniel.Koboldt@nationwidechildrens.org.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA. Daniel.Koboldt@nationwidechildrens.org.
Jazyk: angličtina
Zdroj: NPJ genomic medicine [NPJ Genom Med] 2024 Dec 18; Vol. 9 (1), pp. 66. Date of Electronic Publication: 2024 Dec 18.
DOI: 10.1038/s41525-024-00454-4
Abstrakt: 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.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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