Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects

Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are...
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Autor*in:	Qun Li [verfasserIn] Lin Zhao [verfasserIn] Yang Zeng [verfasserIn] Yanping Kuang [verfasserIn] Yichun Guan [verfasserIn] Biaobang Chen [verfasserIn] Shiru Xu [verfasserIn] Bin Tang [verfasserIn] Ling Wu [verfasserIn] Xiaoyan Mao [verfasserIn] Xiaoxi Sun [verfasserIn] Juanzi Shi [verfasserIn] Peng Xu [verfasserIn] Feiyang Diao [verfasserIn] Songguo Xue [verfasserIn] Shihua Bao [verfasserIn] Qingxia Meng [verfasserIn] Ping Yuan [verfasserIn] Wenjun Wang [verfasserIn] Ning Ma [verfasserIn] Di Song [verfasserIn] Bei Xu [verfasserIn] Jie Dong [verfasserIn] Jian Mu [verfasserIn] Zhihua Zhang [verfasserIn] Huizhen Fan [verfasserIn] Hao Gu [verfasserIn] Qiaoli Li [verfasserIn] Lin He [verfasserIn] Li Jin [verfasserIn] Lei Wang [verfasserIn] Qing Sang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Female infertility De novo mutations Reproductive pathways TUBA4A Microtubule stability

Übergeordnetes Werk:	In: Genome Biology - BMC, 2014, 24(2023), 1, Seite 23
Übergeordnetes Werk:	volume:24 ; year:2023 ; number:1 ; pages:23

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13059-023-02894-0

Katalog-ID:	DOAJ089026152

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520			\|a Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.
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allfields	10.1186/s13059-023-02894-0 doi (DE-627)DOAJ089026152 (DE-599)DOAJ7aeded40b7b348c2bfc1fc31390d87f6 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Qun Li verfasserin aut Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility. Female infertility De novo mutations Reproductive pathways TUBA4A Microtubule stability Biology (General) Genetics Lin Zhao verfasserin aut Yang Zeng verfasserin aut Yanping Kuang verfasserin aut Yichun Guan verfasserin aut Biaobang Chen verfasserin aut Shiru Xu verfasserin aut Bin Tang verfasserin aut Ling Wu verfasserin aut Xiaoyan Mao verfasserin aut Xiaoxi Sun verfasserin aut Juanzi Shi verfasserin aut Peng Xu verfasserin aut Feiyang Diao verfasserin aut Songguo Xue verfasserin aut Shihua Bao verfasserin aut Qingxia Meng verfasserin aut Ping Yuan verfasserin aut Wenjun Wang verfasserin aut Ning Ma verfasserin aut Di Song verfasserin aut Bei Xu verfasserin aut Jie Dong verfasserin aut Jian Mu verfasserin aut Zhihua Zhang verfasserin aut Huizhen Fan verfasserin aut Hao Gu verfasserin aut Qiaoli Li verfasserin aut Lin He verfasserin aut Li Jin verfasserin aut Lei Wang verfasserin aut Qing Sang verfasserin aut In Genome Biology BMC, 2014 24(2023), 1, Seite 23 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:24 year:2023 number:1 pages:23 https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/article/7aeded40b7b348c2bfc1fc31390d87f6 kostenfrei https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 23
spelling	10.1186/s13059-023-02894-0 doi (DE-627)DOAJ089026152 (DE-599)DOAJ7aeded40b7b348c2bfc1fc31390d87f6 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Qun Li verfasserin aut Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility. Female infertility De novo mutations Reproductive pathways TUBA4A Microtubule stability Biology (General) Genetics Lin Zhao verfasserin aut Yang Zeng verfasserin aut Yanping Kuang verfasserin aut Yichun Guan verfasserin aut Biaobang Chen verfasserin aut Shiru Xu verfasserin aut Bin Tang verfasserin aut Ling Wu verfasserin aut Xiaoyan Mao verfasserin aut Xiaoxi Sun verfasserin aut Juanzi Shi verfasserin aut Peng Xu verfasserin aut Feiyang Diao verfasserin aut Songguo Xue verfasserin aut Shihua Bao verfasserin aut Qingxia Meng verfasserin aut Ping Yuan verfasserin aut Wenjun Wang verfasserin aut Ning Ma verfasserin aut Di Song verfasserin aut Bei Xu verfasserin aut Jie Dong verfasserin aut Jian Mu verfasserin aut Zhihua Zhang verfasserin aut Huizhen Fan verfasserin aut Hao Gu verfasserin aut Qiaoli Li verfasserin aut Lin He verfasserin aut Li Jin verfasserin aut Lei Wang verfasserin aut Qing Sang verfasserin aut In Genome Biology BMC, 2014 24(2023), 1, Seite 23 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:24 year:2023 number:1 pages:23 https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/article/7aeded40b7b348c2bfc1fc31390d87f6 kostenfrei https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 23
allfields_unstemmed	10.1186/s13059-023-02894-0 doi (DE-627)DOAJ089026152 (DE-599)DOAJ7aeded40b7b348c2bfc1fc31390d87f6 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Qun Li verfasserin aut Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility. Female infertility De novo mutations Reproductive pathways TUBA4A Microtubule stability Biology (General) Genetics Lin Zhao verfasserin aut Yang Zeng verfasserin aut Yanping Kuang verfasserin aut Yichun Guan verfasserin aut Biaobang Chen verfasserin aut Shiru Xu verfasserin aut Bin Tang verfasserin aut Ling Wu verfasserin aut Xiaoyan Mao verfasserin aut Xiaoxi Sun verfasserin aut Juanzi Shi verfasserin aut Peng Xu verfasserin aut Feiyang Diao verfasserin aut Songguo Xue verfasserin aut Shihua Bao verfasserin aut Qingxia Meng verfasserin aut Ping Yuan verfasserin aut Wenjun Wang verfasserin aut Ning Ma verfasserin aut Di Song verfasserin aut Bei Xu verfasserin aut Jie Dong verfasserin aut Jian Mu verfasserin aut Zhihua Zhang verfasserin aut Huizhen Fan verfasserin aut Hao Gu verfasserin aut Qiaoli Li verfasserin aut Lin He verfasserin aut Li Jin verfasserin aut Lei Wang verfasserin aut Qing Sang verfasserin aut In Genome Biology BMC, 2014 24(2023), 1, Seite 23 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:24 year:2023 number:1 pages:23 https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/article/7aeded40b7b348c2bfc1fc31390d87f6 kostenfrei https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 23
allfieldsGer	10.1186/s13059-023-02894-0 doi (DE-627)DOAJ089026152 (DE-599)DOAJ7aeded40b7b348c2bfc1fc31390d87f6 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Qun Li verfasserin aut Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility. Female infertility De novo mutations Reproductive pathways TUBA4A Microtubule stability Biology (General) Genetics Lin Zhao verfasserin aut Yang Zeng verfasserin aut Yanping Kuang verfasserin aut Yichun Guan verfasserin aut Biaobang Chen verfasserin aut Shiru Xu verfasserin aut Bin Tang verfasserin aut Ling Wu verfasserin aut Xiaoyan Mao verfasserin aut Xiaoxi Sun verfasserin aut Juanzi Shi verfasserin aut Peng Xu verfasserin aut Feiyang Diao verfasserin aut Songguo Xue verfasserin aut Shihua Bao verfasserin aut Qingxia Meng verfasserin aut Ping Yuan verfasserin aut Wenjun Wang verfasserin aut Ning Ma verfasserin aut Di Song verfasserin aut Bei Xu verfasserin aut Jie Dong verfasserin aut Jian Mu verfasserin aut Zhihua Zhang verfasserin aut Huizhen Fan verfasserin aut Hao Gu verfasserin aut Qiaoli Li verfasserin aut Lin He verfasserin aut Li Jin verfasserin aut Lei Wang verfasserin aut Qing Sang verfasserin aut In Genome Biology BMC, 2014 24(2023), 1, Seite 23 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:24 year:2023 number:1 pages:23 https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/article/7aeded40b7b348c2bfc1fc31390d87f6 kostenfrei https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 23
allfieldsSound	10.1186/s13059-023-02894-0 doi (DE-627)DOAJ089026152 (DE-599)DOAJ7aeded40b7b348c2bfc1fc31390d87f6 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Qun Li verfasserin aut Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility. Female infertility De novo mutations Reproductive pathways TUBA4A Microtubule stability Biology (General) Genetics Lin Zhao verfasserin aut Yang Zeng verfasserin aut Yanping Kuang verfasserin aut Yichun Guan verfasserin aut Biaobang Chen verfasserin aut Shiru Xu verfasserin aut Bin Tang verfasserin aut Ling Wu verfasserin aut Xiaoyan Mao verfasserin aut Xiaoxi Sun verfasserin aut Juanzi Shi verfasserin aut Peng Xu verfasserin aut Feiyang Diao verfasserin aut Songguo Xue verfasserin aut Shihua Bao verfasserin aut Qingxia Meng verfasserin aut Ping Yuan verfasserin aut Wenjun Wang verfasserin aut Ning Ma verfasserin aut Di Song verfasserin aut Bei Xu verfasserin aut Jie Dong verfasserin aut Jian Mu verfasserin aut Zhihua Zhang verfasserin aut Huizhen Fan verfasserin aut Hao Gu verfasserin aut Qiaoli Li verfasserin aut Lin He verfasserin aut Li Jin verfasserin aut Lei Wang verfasserin aut Qing Sang verfasserin aut In Genome Biology BMC, 2014 24(2023), 1, Seite 23 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:24 year:2023 number:1 pages:23 https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/article/7aeded40b7b348c2bfc1fc31390d87f6 kostenfrei https://doi.org/10.1186/s13059-023-02894-0 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 23
language	English
source	In Genome Biology 24(2023), 1, Seite 23 volume:24 year:2023 number:1 pages:23
sourceStr	In Genome Biology 24(2023), 1, Seite 23 volume:24 year:2023 number:1 pages:23
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Female infertility De novo mutations Reproductive pathways TUBA4A Microtubule stability Biology (General) Genetics
isfreeaccess_bool	true
container_title	Genome Biology
authorswithroles_txt_mv	Qun Li @@aut@@ Lin Zhao @@aut@@ Yang Zeng @@aut@@ Yanping Kuang @@aut@@ Yichun Guan @@aut@@ Biaobang Chen @@aut@@ Shiru Xu @@aut@@ Bin Tang @@aut@@ Ling Wu @@aut@@ Xiaoyan Mao @@aut@@ Xiaoxi Sun @@aut@@ Juanzi Shi @@aut@@ Peng Xu @@aut@@ Feiyang Diao @@aut@@ Songguo Xue @@aut@@ Shihua Bao @@aut@@ Qingxia Meng @@aut@@ Ping Yuan @@aut@@ Wenjun Wang @@aut@@ Ning Ma @@aut@@ Di Song @@aut@@ Bei Xu @@aut@@ Jie Dong @@aut@@ Jian Mu @@aut@@ Zhihua Zhang @@aut@@ Huizhen Fan @@aut@@ Hao Gu @@aut@@ Qiaoli Li @@aut@@ Lin He @@aut@@ Li Jin @@aut@@ Lei Wang @@aut@@ Qing Sang @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	326173617
id	DOAJ089026152
language_de	englisch
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callnumber-first	Q - Science
author	Qun Li
spellingShingle	Qun Li misc QH301-705.5 misc QH426-470 misc Female infertility misc De novo mutations misc Reproductive pathways misc TUBA4A misc Microtubule stability misc Biology (General) misc Genetics Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects
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topic_title	QH301-705.5 QH426-470 Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects Female infertility De novo mutations Reproductive pathways TUBA4A Microtubule stability
topic	misc QH301-705.5 misc QH426-470 misc Female infertility misc De novo mutations misc Reproductive pathways misc TUBA4A misc Microtubule stability misc Biology (General) misc Genetics
topic_unstemmed	misc QH301-705.5 misc QH426-470 misc Female infertility misc De novo mutations misc Reproductive pathways misc TUBA4A misc Microtubule stability misc Biology (General) misc Genetics
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title	Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects
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title_full	Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects
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author_browse	Qun Li Lin Zhao Yang Zeng Yanping Kuang Yichun Guan Biaobang Chen Shiru Xu Bin Tang Ling Wu Xiaoyan Mao Xiaoxi Sun Juanzi Shi Peng Xu Feiyang Diao Songguo Xue Shihua Bao Qingxia Meng Ping Yuan Wenjun Wang Ning Ma Di Song Bei Xu Jie Dong Jian Mu Zhihua Zhang Huizhen Fan Hao Gu Qiaoli Li Lin He Li Jin Lei Wang Qing Sang
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title_sort	large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects
callnumber	QH301-705.5
title_auth	Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects
abstract	Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.
abstractGer	Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.
abstract_unstemmed	Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.
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title_short	Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects
url	https://doi.org/10.1186/s13059-023-02894-0 https://doaj.org/article/7aeded40b7b348c2bfc1fc31390d87f6 https://doaj.org/toc/1474-760X
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author2	Lin Zhao Yang Zeng Yanping Kuang Yichun Guan Biaobang Chen Shiru Xu Bin Tang Ling Wu Xiaoyan Mao Xiaoxi Sun Juanzi Shi Peng Xu Feiyang Diao Songguo Xue Shihua Bao Qingxia Meng Ping Yuan Wenjun Wang Ning Ma Di Song Bei Xu Jie Dong Jian Mu Zhihua Zhang Huizhen Fan Hao Gu Qiaoli Li Lin He Li Jin Lei Wang Qing Sang
author2Str	Lin Zhao Yang Zeng Yanping Kuang Yichun Guan Biaobang Chen Shiru Xu Bin Tang Ling Wu Xiaoyan Mao Xiaoxi Sun Juanzi Shi Peng Xu Feiyang Diao Songguo Xue Shihua Bao Qingxia Meng Ping Yuan Wenjun Wang Ning Ma Di Song Bei Xu Jie Dong Jian Mu Zhihua Zhang Huizhen Fan Hao Gu Qiaoli Li Lin He Li Jin Lei Wang Qing Sang
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up_date	2024-07-03T20:49:37.295Z
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Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects

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