title: Yeast model identifies ENTPD6 as a potential non-obstructive azoospermia pathogenic gene.
abstract: Approximately ten percent of male infertility is caused by non-obstructive azoospermia (NOA), but the etiologies of many NOA remain elusive. Recently, a genome-wide association study (GWAS) of NOA in Han Chinese men was conducted, and only a few genetic variants associated with NOA were found, which might have resulted from genetic heterogeneity. However, those variants that lack genome-wide significance might still be essential for fertility. Functional analysis of genes surrounding these variants in Drosophila identified some spermatogenesis-essential genes. As a complementary method of Drosophila screening, SK1 background Saccharomvces cerevisiae was used as a model to screen meiosis-related genes from the NOA GWAS data in this study. After functional screening, GDA1 (orthologous to humanENTPD6) was found to be a novel meiosis-related gene. The deletion of GDA1 resulted in the failure of yeast sporulation. Further investigations showed that Gda1p was important for pre-meiotic S phase entry. Interestingly, the meiotic role of Gda1p was dependent on its guanosine diphosphatase activity, but not it's cytoplasmic, transmembrane or stem domains. These yeast data suggest that ENTPD6 may be a novel meiosis-associated NOA-related gene, and the yeast model provides a good approach to analyze GWAS results of NOA.
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chaoming
authors.initials: C
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Guo
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] College of Marine Life, Ocean University of China, Qingdao 266003, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Haichao
authors.initials: H
authors.lastname: Zhao
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: 1] State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zuomin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: College of Marine Life, Ocean University of China, Qingdao 266003, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: 1] State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: 1] State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D053713:Azoospermia / Q000235:genetics* / Q000473:pathology; D055106:Genome-Wide Association Study; D006031:Glycosylation; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C080326:IME1 protein, S cerevisiae; D009687:Nuclear Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C561876:ENTPD6 protein, human; D011755:Pyrophosphatases; C010357:guanosine-diphosphatase