{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T02:28:55Z","timestamp":1786328935393,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009741","name":"National Blood Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009741","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL147879"],"award-info":[{"award-number":["HL147879"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL169401"],"award-info":[{"award-number":["HL169401"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA021765"],"award-info":[{"award-number":["CA021765"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vox Sanguinis"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>\n                      <jats:italic>RHD*03N.01 (RHD*DIIIa\u2010CEVS(4\u20107)\u2010D)<\/jats:italic>\n                      and\n                      <jats:italic>RHD*01N.06(RHD*D\u2010CEVS(4\u20107)\u2010D)<\/jats:italic>\n                      are hybrid alleles that encode a partial C antigen, resulting in increased risk of C alloimmunization in individuals without a conventional C antigen. As detection of the hybrid alleles remains challenging, new markers can aid accurate identification, ensuring provision of C\u2010negative blood to individuals at risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      To identify breakpoint regions and distinct intronic single nucleotide variations (SNVs) of the hybrid alleles, Pacific Bioscience (PacBio) long\u2010read sequencing was performed in two patients with\n                      <jats:italic>RHD*DIIIa\u2010CEVS(4\u20107)\u2010D<\/jats:italic>\n                      and one patient with\n                      <jats:italic>RHD*D\u2010CEVS(4\u20107)\u2010D<\/jats:italic>\n                      ; two patients without hybrid alleles served as controls. Association of the identified SNVs with\n                      <jats:italic>RHD*DIIIa\u2010CEVS(4\u20107)\u2010D<\/jats:italic>\n                      was subsequently evaluated in 910 patients with sickle cell disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The 5\u2032 breakpoint region of\n                      <jats:italic>RHD*DIIIa\u2010CEVS(4\u20107)\u2010D<\/jats:italic>\n                      was found in intron 3 at chr1:25293827\u201325293837 (\n                      <jats:italic>RHD<\/jats:italic>\n                      c.486+3036\u20133046) and chr1:25293907\u201325293980 (\n                      <jats:italic>RHD<\/jats:italic>\n                      c. 486+3116\u20133189) for the two patients. The 5\u2032 breakpoint region of\n                      <jats:italic>RHD*D\u2010CEVS(4\u20107)\u2010D<\/jats:italic>\n                      was at chr1:25294633\u201325295072 (\n                      <jats:italic>RHD<\/jats:italic>\n                      c.486+3842\u20134281). Both hybrid alleles had identical 3\u2032 breakpoint region in intron 7 at chr1:25310252\u201325310377 (\n                      <jats:italic>RHD<\/jats:italic>\n                      c.1073+3523\u20133648). Three intronic SNVs were found in\n                      <jats:italic>RHD*DIIIa\u2010CEVS(4\u20107)\u2010D<\/jats:italic>\n                      : chr1:25293603 (\n                      <jats:italic>RHD<\/jats:italic>\n                      c.486+2812) G&gt;A, chr1:25293891 (\n                      <jats:italic>RHD<\/jats:italic>\n                      c.486+3100) A&gt;G in intron 3; chr1:25310934 (\n                      <jats:italic>RHD<\/jats:italic>\n                      c.1073+4205) T&gt;C in intron 7. In 910 patients, the SNVs demonstrated high sensitivities (94.83%, 94.83%, 96.55%) and specificities (99.88%, 99.88%, 99.88%) in detecting\n                      <jats:italic>RHD*DIIIa\u2010CEVS(4\u20107)\u2010D<\/jats:italic>\n                      . One SNV, chr1:25294894 (\n                      <jats:italic>RHD<\/jats:italic>\n                      c.486+4103) T&gt;C in intron 3, was identified in\n                      <jats:italic>RHD*D\u2010CEVS(4\u20107)\u2010D<\/jats:italic>\n                      , but not confirmed due to lack of additional carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Three intronic SNVs can be used to accurately identify\n                      <jats:italic>RHD*DIIIa\u2010CEVS(4\u20107)\u2010D<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/vox.70292","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:46:12Z","timestamp":1779695172000},"page":"1235-1244","source":"Crossref","is-referenced-by-count":0,"title":["Identification of breakpoint regions and single nucleotide variations of\n                    <i>RHD<\/i>\n                    hybrid alleles by long\u2010read sequencing"],"prefix":"10.1111","volume":"121","author":[{"given":"Ti\u2010Cheng","family":"Chang","sequence":"first","affiliation":[{"name":"Center for Applied Bioinformatics St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bensheng","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Computational Biology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teha","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude 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