• PMID: 26152596
• Gene Name: ENTPD6
• Condition: Non-obstructive azoospermia (NOA)
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Non-obstructive azoospermia (NOA)

Yeast model identifies ENTPD6 as a potential non-obstructive azoospermia pathogenic gene

Wang Q, Liu C, Tang C, Guo H, Liu Y, Wang L, Zhao H, Shang Y, Wen Y, Lin Y, Zhou T, Zhou Z, Dong W, Hu Z, Guo X, Sha J, Li W.

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. FAU - Wang, Qian AU - Wang Q AD - 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. FAU - Liu, Chao AU - Liu C AD - 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. FAU - Tang, Chaoming AU - Tang C AD - 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. FAU - Guo, Huiping AU - Guo H AD - State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. FAU - Liu, Yujiao AU - Liu Y AD - 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. FAU - Wang, Lina AU - Wang L AD - 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. FAU - Zhao, Haichao AU - Zhao H AD - 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. FAU - Shang, Yongliang AU - Shang Y AD - 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. FAU - Wen, Yang AU - Wen Y AD - State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China. FAU - Lin, Yuan AU - Lin Y AD - State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China. FAU - Zhou, Tao AU - Zhou T AD - State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China. FAU - Zhou, Zuomin AU - Zhou Z AD - 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. FAU - Dong, Wen AU - Dong W AD - College of Marine Life, Ocean University of China, Qingdao 266003, China. FAU - Hu, Zhibin AU - Hu Z AD - State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Nanjing Medical University, Nanjing 210029, China. FAU - Guo, Xuejiang AU - Guo X AD - 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. FAU - Sha, Jiahao AU - Sha J AD - 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.