{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:57:21Z","timestamp":1790852241878,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":273,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013101","name":"National Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013101","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Structural variants (SVs) comprise copy\u2010number variants (e.g., deletions and duplications) and copy\u2010neutral SV (e.g., perfect inversions). Short\u2010read high\u2010throughput DNA\u2010sequencing is the established technology for small\u2010variant calling in clinical genomics, whereas Oxford nanopore or PacBio long\u2010read NGS technologies improve SV identification but remain challenging to implement in clinical settings. We developed and validated a novel experimental protocol and bioinformatics pipeline for SV genotyping from short\u2010read whole\u2010genome sequencing (WGS) of restriction\u2010circles of DNA. The experimental protocol includes\n                    <jats:italic>Bcl<\/jats:italic>\n                    I\u2010restriction digestion of genomic DNA, fragment\u2010ends ligation and short\u2010read WGS. The bioinformatics pipeline takes advantage of linking pair\u2010end reads (LPERs), a key operator associating terminal sequences from each restriction fragment. LPERs contain long\u2010distance haplotype information, essential for SV\u2010genotyping. Each SV associates with a specific LPER pattern. The approach was applied to a patient with Duchenne muscular dystrophy (DMD) generating proper LPER vertical (8.6x) and horizontal (83%) coverages with good quality standards. SV\u2010specific LPER quality filters were designed to improve the consistency of SV detection. The approach was validated by verifying a previously characterised\n                    <jats:italic>DMD<\/jats:italic>\n                    \u2010genotype in the proband (\n                    <jats:italic>DMD<\/jats:italic>\n                    _exons_45\u201054 deletion and\n                    <jats:italic>DMD<\/jats:italic>\n                    _exons_38\u201043 duplication) with our output. Conventional SV genotyping using other SV detection algorithms can still be successfully applied to complete an accurate definition of the rearrangement. Our SV\u2010genotyping algorithm detected two novel SVs in Xq28, which were verified by direct molecular investigation, and resulted polymorphic in the general population: a 1.4\u2009kb deletion, allelic frequency AF (CI95%) of 0.83 (0.71\u20130.91) and a perfect inversion with 0.31 (0.08\u20130.54) originated by recombination of 99% homologous 8.4\u2009kb inverted repeats (IRs). Although IR\u2010mediated inversions represent a major challenge for WGS\u2010based genotyping, our approach correctly indicated the absence of haemophilia recurrent inversions. Additionally, our protocol allows application of regular small\u2010variant calling. A likely benign SNV in\n                    <jats:italic>F8<\/jats:italic>\n                    \u2010intron\u20103 was also identified and verified. The potential clinical utility of this approach is supported by its consistency and ability to improve SV genotyping whilst allowing the application of conventional variant calling algorithms.\n                  <\/jats:p>","DOI":"10.1155\/humu\/2169350","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:13:24Z","timestamp":1790849604000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Strategy for Structural Variant Genotyping by Short\u2010Read Genomic Sequencing From Restriction\u2010Circles: Experimental and Bioinformatics Proof\u2010of\u2010Concept"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-9414","authenticated-orcid":false,"given":"Miguel M.","family":"Abelleyro","sequence":"first","affiliation":[{"name":"Institute of Experimental Medicine (IMEX)  Autonomous City of Buenos Aires 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Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2956-2907","authenticated-orcid":false,"given":"Leonela","family":"Luce","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry (FFyB) University of Buenos Aires (UBA)  Autonomous City of Buenos Aires Argentina  uba.ar"},{"name":"Institute of Immunology Genetics and Metabolism (INIGEM) CONICET-University of Buenos Aires (UBA)  Autonomous City of Buenos Aires Argentina"},{"name":"John Walton Muscular Dystrophy Research Centre Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1933-2031","authenticated-orcid":false,"given":"H\u00e9ctor M.","family":"Cifuentes","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX)  Autonomous City of Buenos Aires Argentina"},{"name":"Patagonian Hospital Translational Knowledge Unit El Calafate High Complexity Hospital-SAMIC  El Calafate Santa Cruz Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3901-3904","authenticated-orcid":false,"given":"Claudia P.","family":"Radic","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX)  Autonomous City of Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4683-7899","authenticated-orcid":false,"given":"Liliana C.","family":"Rossetti","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX)  Autonomous City of Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5026-5486","authenticated-orcid":false,"given":"Florencia","family":"Giliberto","sequence":"additional","affiliation":[{"name":"Faculty 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