{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:47:07Z","timestamp":1773028027700,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K07873"],"award-info":[{"award-number":["21K07873"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H06279"],"award-info":[{"award-number":["16H06279"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Most chromosomal aberrations revealed by chromosomal microarray testing (CMA) are simple; however, very complex chromosomal structural rearrangements can also be found. Although the mechanism of structural rearrangements has been gradually revealed, not all mechanisms have been elucidated. We analyzed the breakpoint\u2010junctions (BJs) of two or more clustered copy number variations (CNVs) in the same chromosome arms to understand their conformation and the mechanism of complex structural rearrangements. Combining CMA with long\u2010read whole\u2010genome sequencing (WGS) analysis, we successfully determined all BJs for the clustered CNVs identified in four patients. Multiple CNVs were intricately intertwined with each other, and clustered CNVs in four patients were involved in global complex chromosomal rearrangements. The BJs of two clustered deletions identified in two patients showed microhomologies, and their characteristics were explained by chromothripsis. In contrast, the BJs in the other two patients, who showed clustered deletions and duplications, consisted of blunt\u2010end and nontemplated insertions. These findings could be explained only by alternative nonhomologous end\u2010joining, a mechanism related to polymerase theta. All the patients had at least one inverted segment. Three patients showed cryptic aberrations involving a disruption and a deletion\/duplication, which were not detected by CMA but were first identified by WGS. This result suggested that complex rearrangements should be considered if clustered CNVs are observed in the same chromosome arms. Because CMA has potential limitations in genotype\u2013phenotype correlation analysis, a more detailed analysis by whole genome examination is recommended in cases of suspected complex structural aberrations.<\/jats:p>","DOI":"10.1002\/ajmg.a.62997","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T12:30:00Z","timestamp":1666701000000},"page":"112-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Long\u2010read sequence analysis for clustered genomic copy number aberrations revealed architectures of intricately intertwined rearrangements"],"prefix":"10.1002","volume":"191","author":[{"given":"Takeaki","family":"Tamura","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Child Health Nihon University School of Medicine  Tokyo Japan"},{"name":"Division of Gene Medicine, Graduate School of Medical Science Tokyo Women's Medical University  Tokyo 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National Institute of Genetics  Mishima Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Gene Medicine, Graduate School of Medical Science Tokyo Women's Medical University  Tokyo Japan"},{"name":"Institute of Medical Genetics, Tokyo Women's Medical University  Tokyo 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