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dc.contributor.authorFarrar, Gwyneth
dc.date.accessioned2023-05-23T14:36:30Z
dc.date.available2023-05-23T14:36:30Z
dc.date.issued2022
dc.date.submitted2022en
dc.identifier.citationHitti-Malin, R.J. and Dhaenens, C.-M. and Panneman, D.M. and Corradi, Z. and Khan, M. and den Hollander, A.I. and Farrar, G.J. and Gilissen, C. and Hoischen, A. and van de Vorst, M. and Bults, F. and Boonen, E.G.M. and Saunders, P. and Roosing, S. and Cremers, F.P.M., Using single molecule Molecular Inversion Probes as a cost-effective, high-throughput sequencing approach to target all genes and loci associated with macular diseases, Human Mutation, 2022 Dec;43(12):2234-2250en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/102708
dc.description.abstractMacular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs-based sequencing of all MD-associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 iMD and AMD-associated genes and noncoding or regulatory loci, known pseudo-exons, and the mitochondrial genome in two test cohorts that were previously screened for variants in ABCA4. Following detailed sequencing analysis of 110 probands, a diagnostic yield of 38% was observed. This established an ‘‘MD-smMIPs panel,” enabling a genotype-first approach in a high-throughput and cost-effective manner, whilst achieving uniform and high coverage across targets. Further analysis will identify known and novel variants in MD-associated genes to offer an accurate clinical diagnosis to patients. Furthermore, this will reveal new genetic associations for MD and potential genetic overlaps between iMD and AMDen
dc.format.extent2234-2250en
dc.language.isoenen
dc.relation.ispartofseriesHuman Mutation;
dc.relation.ispartofseries43;
dc.relation.ispartofseries12;
dc.rightsYen
dc.subjectCost-effectiveen
dc.subjectHigh-throughputen
dc.subjectMacular diseasesen
dc.subjectsmMIPsen
dc.subjectTargeted gene sequencingen
dc.titleUsing single molecule Molecular Inversion Probes as a cost-effective, high-throughput sequencing approach to target all genes and loci associated with macular diseasesen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/gjfarrar
dc.identifier.rssinternalid251065
dc.identifier.doihttp://dx.doi.org/10.1002/humu.24489
dc.rights.ecaccessrightsopenAccess


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