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A Homozygous Ancestral SVA-Insertion-Mediated Deletion in WDR66 Induces Multiple Morphological Abnormalities of the Sperm Flagellum and Male Infertility.

dc.rights.licenseopenen_US
dc.contributor.authorKHERRAF, Zine-Eddine
dc.contributor.authorAMIRI-YEKTA, Amir
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorDACHEUX, Denis
dc.contributor.authorKARAOUZÈNE, Thomas
dc.contributor.authorCOUTTON, Charles
dc.contributor.authorCHRISTOU-KENT, Marie
dc.contributor.authorMARTINEZ, Guillaume
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorLANDREIN, Nicolas
dc.contributor.authorLE TANNO, Pauline
dc.contributor.authorFOURATI BEN MUSTAPHA, Selima
dc.contributor.authorHALOUANI, Lazhar
dc.contributor.authorOUAFI, Marrakchi
dc.contributor.authorMAKNI, Mounir
dc.contributor.authorLATROUS, Habib
dc.contributor.authorKHAROUF, Mahmoud
dc.contributor.authorPERNET-GALLAY, Karine
dc.contributor.authorGOURABI, Hamid
dc.contributor.authorROBINSON, Derrick R
dc.contributor.authorCROUZY, Serge
dc.contributor.authorBLUM, Michael
dc.contributor.authorTHIERRY-MIEG, Nicolas
dc.contributor.authorTOURÉ, Aminata
dc.contributor.authorZOUARI, Raoudha
dc.contributor.authorARNOULT, Christophe
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBONHIVERS, Melanie
dc.contributor.authorRAY, Pierre F.
dc.date.accessioned2023-06-21T14:14:27Z
dc.date.available2023-06-21T14:14:27Z
dc.date.issued2018-09-06
dc.identifier.issn0002-9297en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182751
dc.description.abstractEnMultiple morphological abnormalities of the sperm flagellum (MMAF) is a severe form of male infertility defined by the presence of a mosaic of anomalies, including short, bent, curled, thick, or absent flagella, resulting from a severe disorganization of the axoneme and of the peri-axonemal structures. Mutations in DNAH1, CFAP43, and CFAP44, three genes encoding axoneme-related proteins, have been described to account for approximately 30% of the MMAF cases reported so far. Here, we searched for pathological copy-number variants in whole-exome sequencing data from a cohort of 78 MMAF-affected subjects to identify additional genes associated with MMAF. In 7 of 78 affected individuals, we identified a homozygous deletion that removes the two penultimate exons of WDR66 (also named CFAP251), a gene coding for an axonemal protein preferentially localized in the testis and described to localize to the calmodulin- and spoke-associated complex at the base of radial spoke 3. Sequence analysis of the breakpoint region revealed in all deleted subjects the presence of a single chimeric SVA (SINE-VNTR-Alu) at the breakpoint site, suggesting that the initial deletion event was potentially mediated by an SVA insertion-recombination mechanism. Study of Trypanosoma WDR66's ortholog (TbWDR66) highlighted high sequence and structural analogy with the human protein and confirmed axonemal localization of the protein. Reproduction of the human deletion in TbWDR66 impaired flagellar movement, thus confirming WDR66 as a gene associated with the MMAF phenotype and highlighting the importance of the WDR66 C-terminal region.
dc.language.isoENen_US
dc.subject.enmale infertility
dc.subject.enmultiple morphological anomalies of the sperm flagella
dc.subject.enaxoneme
dc.subject.ensperm flagella
dc.subject.enMMAF
dc.subject.enspermatogenesis
dc.title.enA Homozygous Ancestral SVA-Insertion-Mediated Deletion in WDR66 Induces Multiple Morphological Abnormalities of the Sperm Flagellum and Male Infertility.
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.ajhg.2018.07.014en_US
dc.subject.halSciences du Vivant [q-bio]/Biologie de la reproductionen_US
dc.subject.halSciences du Vivant [q-bio]/Génétique/Génétique humaineen_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologie/Physiologie [q-bio.TO]en_US
bordeaux.journalAmerican Journal of Human Geneticsen_US
bordeaux.page400-412en_US
bordeaux.volume103en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue3en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-01863586
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=American%20Journal%20of%20Human%20Genetics&rft.date=2018-09-06&rft.volume=103&rft.issue=3&rft.spage=400-412&rft.epage=400-412&rft.eissn=0002-9297&rft.issn=0002-9297&rft.au=KHERRAF,%20Zine-Eddine&AMIRI-YEKTA,%20Amir&DACHEUX,%20Denis&KARAOUZ%C3%88NE,%20Thomas&COUTTON,%20Charles&rft.genre=article


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