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.
Highlights
Infertility, which is a severe threat for the continuation of humans, affects one-sixth of couples worldwide[1,2]
We found that the sporulation efficiency of the gda1Δ strain showed a significant decrease compared with that of the wild type (WT) strain (Fig. 1b–d), which is similar to some non-obstructive azoospermia (NOA) of humans
Hundreds of tag single nucleotide polymorphisms have been found to be associated with human diseases by genome-wide association studies[10], and genome-wide association study (GWAS) provides a good approach to study the associations between tSNPs and traits such as major diseases[10,11]
Summary
Infertility, which is a severe threat for the continuation of humans, affects one-sixth of couples worldwide[1,2]. As a simple single-cell eukaryote, Saccharomvces cerevisiae is widely used as a model organism in biological research and has offered valuable knowledge of the genetics and basic cellular processes that are evolutionarily conserved with higher eukaryotes, such as the cell cycle, DNA replication, recombination, metabolism, aging and meiosis[14,15,16,17] Many of these results have been directly extended to mammalian systems, providing an important tool in understanding complex human diseases[18,19,20]. As a classical model for meiotic studies[17], functional genomic screening in Saccharomvces cerevisiae provides an efficient and convenient method to identify meiosis-associated genes that might be evolutionarily conserved from yeast to humans. ENTPD6, the human ortholog of GDA1, may be a NOA pathogenic gene
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
