{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:44:06Z","timestamp":1783748646518,"version":"3.55.0"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Element Biosciences"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Whole genome sequencing has been an effective tool in the discovery of variants that cause rare diseases. In this study, we determined the suitability of a novel avidity sequencing approach for rare disease applications. We built a sample to results workflow, combining this sequencing technology with standard library preparation kits, analysis workflows, and interpretation tools. We applied the workflow to ten pedigrees with inherited retinal degeneration (IRD) phenotype. Candidate variants of interest identified through whole genome sequencing were further evaluated using segregation analysis in the additional family members. Potentially causal variants in known IRD genes were detected in five of the ten cases. These high confidence variants were found in\n                    <jats:italic>ABCA4<\/jats:italic>\n                    ,\n                    <jats:italic>CERKL<\/jats:italic>\n                    ,\n                    <jats:italic>MAK<\/jats:italic>\n                    ,\n                    <jats:italic>PEX6<\/jats:italic>\n                    and\n                    <jats:italic>RDH12<\/jats:italic>\n                    genes associated with retinal degeneration, that could be sufficient to cause pathology. Pending confirmatory clinical evaluation, we observed a 50% diagnostic yield, consistent with previously reported outcomes of IRD patient analysis. The study confirms that avidity sequencing is effective in detection of causal variants when used for whole genome sequencing in rare disease applications.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0307266","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T13:28:52Z","timestamp":1728048532000},"page":"e0307266","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Avidity sequencing of whole genomes from retinal degeneration pedigrees identifies causal variants"],"prefix":"10.1371","volume":"19","author":[{"given":"Pooja","family":"Biswas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adda","family":"Villanueva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Krajacich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Lazaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan R.","family":"Lajoie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8353-1506","authenticated-orcid":true,"given":"Semyon","family":"Kruglyak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radha","family":"Ayyagari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"pone.0307266.ref001","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1002\/ajmg.a.61124","article-title":"The burden of rare diseases","volume":"179","author":"CR Ferreira","year":"2019","journal-title":"Am J Med Genet A"},{"key":"pone.0307266.ref002","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ajhg.2016.12.003","article-title":"Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease","volume":"100","author":"KJ Carss","year":"2017","journal-title":"Am J Hum Genet"},{"key":"pone.0307266.ref003","first-page":"1007","volume":"20","author":"EF Sanford","year":"2019","journal-title":"Rapid Whole Genome Sequencing Has Clinical Utility in Children in the PICU*: Pediatr Crit Care Med"},{"key":"pone.0307266.ref004","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/s41431-022-01113-x","article-title":"Recommendations for whole genome sequencing in diagnostics for rare diseases","volume":"30","author":"E Souche","year":"2022","journal-title":"Eur J Hum Genet"},{"key":"pone.0307266.ref005","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13073-021-00855-5","article-title":"Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients","volume":"13","author":"H Stranneheim","year":"2021","journal-title":"Genome Med"},{"key":"pone.0307266.ref006","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41586-020-2434-2","article-title":"Whole-genome sequencing of patients with rare diseases in a national health system","volume":"583","author":"E Turro","year":"2020","journal-title":"Nature"},{"key":"pone.0307266.ref007","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S2213-2600(15)00139-3","article-title":"Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings","volume":"3","author":"LK Willig","year":"2015","journal-title":"Lancet Respir Med"},{"key":"pone.0307266.ref008","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrg.2017.116","article-title":"Paediatric genomics: diagnosing rare disease in children","volume":"19","author":"CF Wright","year":"2018","journal-title":"Nat Rev Genet"},{"key":"pone.0307266.ref009","doi-asserted-by":"crossref","unstructured":"The 100,000 Genomes Project Pilot Investigators, Smedley D, Smith KR, Martin A, Thomas EA, McDonagh EM, et al. 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care\u2014Preliminary Report. 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