Dataset Information

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.

SUBMITTER: Wang Q

PROVIDER: S-EPMC4495445 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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

Wang Qian Q Liu Chao C Tang Chaoming C Guo Huiping H Liu Yujiao Y Wang Lina L Zhao Haichao H Shang Yongliang Y Wen Yang Y Lin Yuan Y Zhou Tao T Zhou Zuomin Z Dong Wen W Hu Zhibin Z Guo Xuejiang X Sha Jiahao J Li Wei W

Scientific reports 20150708

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 varia ...[more]

PMID: 26152596

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Project description:BackgroundNon-obstructive azoospermia (NOA) is a disease related to spermatogenic disorders. Currently, the specific etiological mechanism of NOA is unclear. This study aimed to use integrated bioinformatics to screen biomarkers and pathways involved in NOA and reveal their potential molecular mechanisms.MethodsGSE145467 and GSE108886 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NOA tissues and matched obstructive azoospermia (OA) tissues were identified using the GEO2R tool. Common DEGs in the two datasets were screened out by the VennDiagram package. For the functional annotation of common DEGs, DAVID v.6.8 was used to perform Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In accordance with data collected from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, a protein-protein interaction (PPI) network was constructed by Cytoscape. Cytohubba in Cytoscape was used to screen the hub genes. Furthermore, the hub genes were validated based on a separate dataset, GSE9210. Finally, potential micro RNAs (miRNAs) of hub genes were predicted by miRWalk 3.0.ResultsA total of 816 common DEGs, including 52 common upregulated and 764 common downregulated genes in two datasets, were screened out. Some of the more important of these pathways, including focal adhesion, PI3K-Akt signaling pathway, cell cycle, oocyte meiosis, AMP-activated protein kinase (AMPK) signaling pathway, FoxO signaling pathway, and Huntington disease, were involved in spermatogenesis. We further identified the top 20 hub genes from the PPI network, including CCNB2, DYNLL2, HMMR, NEK2, KIF15, DLGAP5, NUF2, TTK, PLK4, PTTG1, PBK, CEP55, CDKN3, CDC25C, MCM4, DNAI1, TYMS, PPP2R1B, DNAI2, and DYNLRB2, which were all downregulated genes. In addition, potential miRNAs of hub genes, including hsa-miR-3666, hsa-miR-130b-3p, hsa-miR-15b-5p, hsa-miR-6838-5p, and hsa-miR-195-5p, were screened out.ConclusionsTaken together, the identification of the above hub genes, miRNAs and pathways will help us better understand the mechanisms associated with NOA, and provide potential biomarkers and therapeutic targets for NOA.

Dataset Information

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

Publications

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

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