{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:59:39Z","timestamp":1790762379836,"version":"4.1.0"},"reference-count":70,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Congenital heart disease (CHD) is the most common birth defect. Ninety percent of isolated cases remain genotype-elusive despite short-read genome sequencing (GS). Our goal was to assess genomic yield with long-read GS compared with short-read GS in CHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We performed Illumina short-read GS on 1101 CHD probands. In a subset of 46 genotype-elusive probands, we performed additional PacBio long-read GS as well as parental sequencing of 7 complete trios. We compared variant calls genome-wide, including across dark and CHD genes in samples with paired short-read and long-read GS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Paired analysis of the 46 probands revealed that genome-wide, long-read GS had 1.01- to 7.93-fold higher call rates of single nucleotide variants, deletions, duplications, and insertions but fewer indels and inversions compared with short-read GS. With a genome-wide sequencing depth of 18.3\u00d7, long-read GS had higher coverage for 10 Tier 1 CHD genes and dark genes, but nonuniform and low sequencing depth (&lt;10\u00d7) in intragenic regions of 4 of these genes. Long-read GS was better able to resolve complex structural variants and the size of large repeat expansions in 59 known disease-causing regions. For example, long-read GS accurately characterized a complex de novo structural variant upstream of\n                      <jats:italic toggle=\"yes\">ZEB2<\/jats:italic>\n                      in a CHD proband who had an extracardiac phenotype overlapping with Mowat-Wilson syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Long-read GS demonstrated higher genome-wide variant call yield compared with short-read GS, better coverage of several cardiac-relevant genes, and better resolution of complex structural variants, including tandem repeat expansions. Long-read GS may provide an option for a subset of patients with CHD who remain genotype-elusive on short-read GS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.125.005305","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:01:13Z","timestamp":1790758873000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Yield of Long-Read Sequencing in Congenital Heart 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