{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:33:23Z","timestamp":1761845603281,"version":"build-2065373602"},"reference-count":17,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:00:00Z","timestamp":1663372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH and the Charles E.H. Upham chair in Pediatrics","doi-asserted-by":"publisher","award":["GM125757","P01 HD070454"],"award-info":[{"award-number":["GM125757","P01 HD070454"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The most prevalent microdeletion in the human population occurs at 22q11.2, a region rich in chromosome-specific low copy repeats (LCR22s). The structure of this region has eluded characterization due to a combination of size, regional complexity, and haplotype diversity. To further complicate matters, it is not well represented in the human reference genome. Most individuals with 22q11.2 deletion syndrome (22q11.2DS) carry a de novo, hemizygous deletion approximately 3 Mbp in size occurring by non-allelic homologous recombination (NAHR) mediated by the LCR22s. The ability to fully delineate an individual\u2019s 22q11.2 regional structure will likely be important for studies designed to assess an unaffected individual\u2019s risk for generating rearrangements in germ cells, potentially leading to offspring with 22q11.2DS. Towards understanding these risk factors, optical mapping has been previously employed to successfully elucidate the structure and variation of LCR22s across 30 families affected by 22q11.2DS. The father in one of these families carries a t(11;22)(q23;q11) translocation. Surprisingly, it was determined that he is the parent-of-deletion-origin. NAHR, which occurred between his der(22) and intact chromosome 22, led to a 22q11.2 deletion in his affected child. The unaffected sibling of the proband with 22q11.2DS inherited the father\u2019s normal chromosome 22, which did not aberrantly recombine. This unexpected observation definitively shows that haplotypes that engage in NAHR can also be inherited intact. This study is the first to identify all structures involving a rearranged chromosome 22 that also participates in NAHR leading to a 22q11.2 deletion.<\/jats:p>","DOI":"10.3390\/genes13091668","type":"journal-article","created":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T23:39:22Z","timestamp":1663544362000},"page":"1668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Non-Allelic Homologous Recombination Event in a Parent with an 11;22 Reciprocal Translocation Leading to 22q11.2 Deletion Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4204-1383","authenticated-orcid":false,"given":"Steven","family":"Pastor","sequence":"first","affiliation":[{"name":"Department of Biomedical and Health Informatics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oanh","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E.","family":"McGinn","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-5458","authenticated-orcid":false,"given":"T. Blaine","family":"Crowley","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine H.","family":"Zackai","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4077-250X","authenticated-orcid":false,"given":"Donna M.","family":"McDonald-McGinn","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly S.","family":"Emanuel","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15071","DOI":"10.1038\/nrdp.2015.71","article-title":"22q11.2 deletion syndrome","volume":"1","author":"Sullivan","year":"2015","journal-title":"Nat. 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