气候变化领域集成服务门户(CCPortal): A TOP6BL mutation abolishes meiotic DNA double-strand break formation and causes human infertility

CCPortal

DOI	10.1016/j.scib.2020.08.026
	A TOP6BL mutation abolishes meiotic DNA double-strand break formation and causes human infertility
	Jiao Y.; Fan S.; Jabeen N.; Zhang H.; Khan R.; Murtaza G.; Jiang H.; Ali A.; Li Y.; Bao J.; Zhang B.; Xu J.; Xu B.; Hussain H.M.J.; Zaman Q.; Khan I.; Bukhari I.; Iqbal F.; Yousaf A.; Dil S.; Khan M.; Ahmad N.; Ma H.; Jiang X.; Zhang Y.; Shi Q.
发表日期	2020
ISSN	20959273
起始页码	2120
结束页码	2129
卷号	65 期号:24
英文摘要	Meiosis is pivotal for sexual reproduction and fertility. Meiotic programmed DNA double-strand breaks (DSBs) initiate homologous recombination, ensuring faithful chromosome segregation and generation of gametes. However, few studies have focused on meiotic DSB formation in human reproduction. Here, we report four infertile siblings born to a consanguineous marriage, with three brothers suffering from non-obstructive azoospermia and one sister suffering from unexplained infertility with normal menstrual cycles and normal ovary sizes with follicular activity. An autosomal recessive mutation in TOP6BL was found co-segregating with infertility in this family. Investigation of one male patient revealed failure in programmed meiotic DSB formation and meiotic arrest prior to pachytene stage of prophase I. Mouse models carrying similar mutations to that in patients recapitulated the spermatogenic abnormalities of the patient. Pathogenicity of the mutation in the female patient was supported by observations in mice that meiotic programmed DSBs failed to form in mutant oocytes and oocyte maturation failure due to absence of meiotic recombination. Our study thus illustrates the phenotypical characteristics and the genotype-phenotype correlations of meiotic DSB formation failure in humans. © 2020 Science China Press
关键词	Human infertility Meiotic arrest Meiotic DSB formation failure Oocyte maturation failure Programmed meiotic DNA double-strand breaks TOP6BLmutation
英文关键词	Cell proliferation; Chromosomes; Mammals; Chromosome segregation; DNA double strand breaks; Homologous recombination; Human reproduction; Meiotic recombinations; Oocyte maturation; Sexual reproduction; Unexplained infertility; Plants (botany)
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207080
作者单位	First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, 230027, China; Institute of Pure and Applied Biology, Zoology Division, Bahauddin Zakariya University, Multan, 60800, Pakistan; Shahbaz Sharif District Hospital, Multan, 60800, Pakistan
推荐引用方式 GB/T 7714	Jiao Y.,Fan S.,Jabeen N.,et al. A TOP6BL mutation abolishes meiotic DNA double-strand break formation and causes human infertility[J],2020,65(24).
APA	Jiao Y..,Fan S..,Jabeen N..,Zhang H..,Khan R..,...&Shi Q..(2020).A TOP6BL mutation abolishes meiotic DNA double-strand break formation and causes human infertility.Science Bulletin,65(24).
MLA	Jiao Y.,et al."A TOP6BL mutation abolishes meiotic DNA double-strand break formation and causes human infertility".Science Bulletin 65.24(2020).