Mutations in TUBB8 and Human Oocyte Meiotic Arrest Feng, Ruizhi Sang, Qing Gupta, Mohan Kuang, Yanping Sun, Xiaoxi Yan, Zheng Zhang, Shaozhen Shi, Juanzi Tian, Guoling Luchniak, Anna Fukuda, Yusuke Li, Bin Yu, Min Chen, Junling Xu, Yao Guo, Luo Qu, Ronggui Wang, Xueqian Sun, Zhaogui Liu, Miao Shi, Huijuan Wang, Hongyan Feng, Yi Shao, Ruijin Chai, Renjie Li, Qiaoli Xing, Qinghe Zhang, Rui Nogales, Eva Jin, Li He, Lin Gupta, Mohan Cowan, Nicholas Wang, Lei
dc.contributor.department Genetics, Development and Cell Biology 2018-02-18T13:12:01.000 2020-06-30T04:01:28Z 2020-06-30T04:01:28Z Fri Jan 01 00:00:00 UTC 2016 2016-01-21
dc.description.abstract <p>BACKGROUND Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown.</p> <p>METHODS We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse- transcriptase–polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes.</p> <p>RESULTS We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes.</p> <p>CONCLUSIONS TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.)</p>
dc.description.comments <p>This article is from <em>The New England Journal of Medicine </em>374 (2016): 223, doi: <a href="" target="_blank">10.1056/NEJMoa1510791</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/
dc.identifier.articleid 1159
dc.identifier.contextkey 10251998
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath gdcb_las_pubs/156
dc.language.iso en
dc.source.bitstream archive/|||Fri Jan 14 20:43:39 UTC 2022
dc.source.uri 10.1056/NEJMoa1510791
dc.subject.disciplines Biochemistry
dc.subject.disciplines Cell Biology
dc.subject.disciplines Developmental Biology
dc.subject.disciplines Genetics and Genomics
dc.subject.disciplines Molecular Biology
dc.title Mutations in TUBB8 and Human Oocyte Meiotic Arrest
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 27a5c4e6-76d2-49c0-ac66-9c829e41cd6a
relation.isOrgUnitOfPublication 9e603b30-6443-4b8e-aff5-57de4a7e4cb2
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
938.07 KB
Adobe Portable Document Format