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dc.contributor.authorCevik-Kaplan, Sebiha
dc.contributor.authorZhao, Pei
dc.contributor.authorZorluer, Atiyye
dc.contributor.authorPir, Mustafa Samet
dc.contributor.authorBian, Wenyin
dc.date.accessioned2024-03-28T09:08:55Z
dc.date.available2024-03-28T09:08:55Z
dc.date.issued2023en_US
dc.identifier.issn2160-1836
dc.identifier.urihttps://doi.org/10.1093/g3journal/jkad227
dc.identifier.urihttps://hdl.handle.net/20.500.12573/2041
dc.description.abstractRapid and low-cost sequencing, as well as computer analysis, have facilitated the diagnosis of many genetic diseases, resulting in a substantial rise in the number of disease-associated genes. However, genetic diagnosis of many disorders remains problematic due to the lack of interpretation for many genetic variants, especially missenses, the infeasibility of high-throughput experiments on mammals, and the shortcomings of computational prediction technologies. Additionally, the available mutant databases are not well-utilized. Toward this end, we used Caenorhabditis elegans mutant resources to delineate the functions of eight missense variants (V444I, V517D, E610K, L732F, E817K, H873P, R1105K, and G1205E) and two stop codons (W937stop and Q1434stop), including several matching variants (MatchVar) with human in ciliopathy associated IFT-140 (also called CHE-11)//IFT140 (intraflagellar transport protein 140). Moreover, MatchVars carrying C. elegans mutants, including IFT-140(G680S) and IFT-140(P702A) for the human (G704S) (dbSNP: rs150745099) and P726A (dbSNP: rs1057518064 and a conflicting variation) were created using CRISPR/Cas9. IFT140 is a key component of IFT complex A (IFT-A), which is involved in the retrograde transport of IFT along cilia and the entrance of G protein-coupled receptors into cilia. Functional analysis of all 10 variants revealed that P702A and W937stop, but not others phenocopied the ciliary phenotypes (short cilia, IFT accumulations, mislocalization of membrane proteins, and cilia entry of nonciliary proteins) of the IFT-140 null mutant, indicating that both P702A and W937stop are phenotypic in C. elegans. Our functional data offered experimental support for interpreting human variants, by using ready-to-use mutants carrying MatchVars and generating MatchVars with CRISPR/Cas9.en_US
dc.language.isoengen_US
dc.publisherGenetics Society of Americaen_US
dc.relation.isversionof10.1093/g3journal/jkad227en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectmatching variantsen_US
dc.subjectciliaen_US
dc.subjectIFT140en_US
dc.subjectciliopathyen_US
dc.subjectMainzer–Saldino syndromeen_US
dc.titleMatching variants for functional characterization of genetic variantsen_US
dc.typearticleen_US
dc.contributor.departmentAGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümüen_US
dc.contributor.authorID0000-0002-0935-1929en_US
dc.contributor.authorID0000-0002-8733-0920en_US
dc.contributor.institutionauthorCevik-Kaplan, Sebiha
dc.contributor.institutionauthorZorluer, Atiyye
dc.contributor.institutionauthorPir, Mustafa Samet
dc.contributor.institutionauthorKaplan, Oktay Ismaıl
dc.identifier.volume13en_US
dc.identifier.issue12en_US
dc.identifier.startpage1en_US
dc.identifier.endpage11en_US
dc.relation.journalG3: Genes, Genomes, Geneticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US


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