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Mutations in TTC29, Encoding an Evolutionarily Conserved Axonemal Protein, Result in Asthenozoospermia and Male Infertility

dc.rights.licenseopenen_US
dc.contributor.authorLORÈS, Patrick
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorDACHEUX, Denis
dc.contributor.authorKHERRAF, Zine-Eddine
dc.contributor.authorNSOTA MBANGO, Jean-Fabrice
dc.contributor.authorCOUTTON, Charles
dc.contributor.authorSTOUVENEL, Laurence
dc.contributor.authorIALY-RADIO, Côme
dc.contributor.authorAMIRI-YEKTA, Amir
dc.contributor.authorWHITFIELD, Marjorie
dc.contributor.authorSCHMITT, Alain
dc.contributor.authorCAZIN, Caroline
dc.contributor.authorGIVELET, Maelle
dc.contributor.authorFERREUX, Lucile
dc.contributor.authorFOURATI BEN MUSTAPHA, Selima
dc.contributor.authorHALOUANI, Lazhar
dc.contributor.authorMARRAKCHI, Ouafi
dc.contributor.authorDANESHIPOUR, Abbas
dc.contributor.authorEL KHOURI, Elma
dc.contributor.authorDO CRUZEIRO, Marcio
dc.contributor.authorFAVIER, Maryline
dc.contributor.authorGUILLONNEAU, Francois
dc.contributor.authorCHAUDHRY, Marhaba
dc.contributor.authorSAKHELI, Zeinab
dc.contributor.authorWOLF, Jean-Philippe
dc.contributor.authorPATRAT, Catherine
dc.contributor.authorGACON, Gérard
dc.contributor.authorSAVINOV, Sergey
dc.contributor.authorHOSSEINI, Seyedeh Hanieh
dc.contributor.authorROBINSON, Derrick
dc.contributor.authorZOUARI, Raoudha
dc.contributor.authorZIYYAT, Ahmed
dc.contributor.authorARNOULT, Christophe
dc.contributor.authorDULIOUST, Emmanuel
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBONHIVERS, Melanie
dc.contributor.authorRAY, Pierre
dc.contributor.authorTOURÉ, Aminata
dc.date.accessioned2023-06-09T11:13:49Z
dc.date.available2023-06-09T11:13:49Z
dc.date.issued2019-11
dc.identifier.issn0002-9297en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182615
dc.description.abstractEnIn humans, structural or functional defects of the sperm flagellum induce asthenozoospermia, which accounts for the main sperm defect encountered in infertile men. Herein we focused on morphological abnormalities of the sperm flagellum (MMAF), a phenotype also termed "short tails," which constitutes one of the most severe sperm morphological defects resulting in asthenozoospermia. In previous work based on whole-exome sequencing of a cohort of 167 MMAF-affected individuals, we identified bi-allelic loss-of-function mutations in more than 30% of the tested subjects. In this study, we further analyzed this cohort and identified five individuals with homozygous truncating variants in TTC29, a gene preferentially and highly expressed in the testis, and encoding a tetratricopeptide repeat-containing protein related to the intraflagellar transport (IFT). One individual carried a frameshift variant, another one carried a homozygous stop-gain variant, and three carried the same splicing variant affecting a consensus donor site. The deleterious effect of this last variant was confirmed on the corresponding transcript and protein product. In addition, we produced and analyzed TTC29 loss-of-function models in the flagellated protist T. brucei and in M. musculus. Both models confirmed the importance of TTC29 for flagellar beating. We showed that in T. brucei the TPR structural motifs, highly conserved between the studied orthologs, are critical for TTC29 axonemal localization and flagellar beating. Overall our work demonstrates that TTC29 is a conserved axonemal protein required for flagellar structure and beating and that TTC29 mutations are a cause of male sterility due to MMAF.
dc.description.sponsorshipLa protéine TAT1 (SLC26A8), partenaire et activateur de CFTR dans le spermatozoïde, au carrefour des infertilités masculines et de la mucoviscidose. - ANR-12-BSV1-0011en_US
dc.description.sponsorshipAlliance française contre les maladies parasitairesen_US
dc.language.isoENen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/
dc.subject.enMMAF
dc.subject.enTPR
dc.subject.enTTC29
dc.subject.enasthenozoospermia
dc.subject.enflagella
dc.subject.eninfertility
dc.subject.enmouse
dc.subject.ensperm
dc.subject.entrypanosome
dc.title.enMutations in TTC29, Encoding an Evolutionarily Conserved Axonemal Protein, Result in Asthenozoospermia and Male Infertility
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.ajhg.2019.10.007en_US
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie moléculaireen_US
dc.subject.halSciences du Vivant [q-bio]/Biologie cellulaire/Interactions cellulaires [q-bio.CB]en_US
dc.subject.halSciences du Vivant [q-bio]/Biologie cellulaire/Organisation et fonctions cellulaires [q-bio.SC]en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Parasitologieen_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Protistologieen_US
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biophysiqueen_US
bordeaux.journalAmerican Journal of Human Geneticsen_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-02370384
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=2019-11&rft.eissn=0002-9297&rft.issn=0002-9297&rft.au=LOR%C3%88S,%20Patrick&DACHEUX,%20Denis&KHERRAF,%20Zine-Eddine&NSOTA%20MBANGO,%20Jean-Fabrice&COUTTON,%20Charles&rft.genre=article


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