Yeast model identifies ENTPD6 as a potential non-obstructive azoospermia pathogenic gene.
Yeast model identifies ENTPD6 as a potential non-obstructive azoospermia pathogenic gene.
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酵母模型将ENTPD6鉴定为潜在的非梗阻性无精子症致病基因
DOI：
10.1038/srep11762
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发表时间：
2015-07-08
影响因子：
4.6
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
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
大约10%的男性不育是由非梗阻性无精子症（NOA）引起的，但许多NOA的病因仍然难以捉摸。近年来，在中国汉族人群中进行了NOA的全基因组关联研究（GWAS），仅发现少数与NOA相关的遗传变异，这可能是遗传异质性所致。然而，那些缺乏全基因组意义的变异可能仍然对生育力至关重要。对果蝇中这些变异体周围的基因进行功能分析，发现了一些精子发生必需基因。作为果蝇筛选的一种补充方法，本研究以SK 1背景果蝇为模型，从NOA GWAS数据中筛选减数分裂相关基因。经过功能筛选，发现GDA 1（与humanENTPD 6同源）是一个新的减数分裂相关基因。GDA 1的缺失导致酵母产孢失败。进一步的研究表明，Gda1p对减数分裂前S期的进入是重要的。有趣的是，Gda1p的减数分裂作用依赖于其鸟苷二磷酸酶活性，而不是它的胞质，跨膜或茎域。这些酵母数据表明ENTPD 6可能是一个新的减数分裂相关的NOA相关基因，酵母模型为分析NOA的GWAS结果提供了一个很好的方法。
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 inDrosophilaidentified some spermatogenesis-essential genes. As a complementary method ofDrosophilascreening, SK1 backgroundSaccharomvces cerevisiaewas 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 ofGDA1resulted 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 thatENTPD6may be a novel meiosis-associated NOA-related gene and the yeast model provides a good approach to analyze GWAS results of NOA.
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影响因子：
2.6
作者：
Gonzalez, Marlyn;Goddard, Noel;Hicks, Charles;Ovalle, Rafael;Rauceo, Jason M.;Jue, Chong K.;Lipke, Peter N.
通讯作者：
Lipke, Peter N.
影响因子：
64.5
作者：
Feldman, RMR;Correll, CC;Deshaies, RJ
通讯作者：
Deshaies, RJ
DOI：
10.1056/nejmra0808700
发表时间：
2009-04-23
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hardy J;Singleton A
通讯作者：
Singleton A
影响因子：
10.5
作者：
Benjamin, KR;Zhang, C;Herskowitz, I
通讯作者：
Herskowitz, I
DOI：
10.1083/jcb.122.2.307
发表时间：
1993-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Abeijon C;Yanagisawa K;Mandon EC;Häusler A;Moremen K;Hirschberg CB;Robbins PW
通讯作者：
Robbins PW