論文 - 詳細
| RRC ID | 32513 |
|---|---|
| 著者 | Yu J, Wu H, Wen Y, Liu Y, Zhou T, Ni B, Lin Y, Dong J, Zhou Z, Hu Z, Guo X, Sha J, Tong C. |
| タイトル | Identification of seven genes essential for male fertility through a genome-wide association study of non-obstructive azoospermia and RNA interference-mediated large-scale functional screening in Drosophila. |
| ジャーナル | Hum Mol Genet |
| Abstract |
Non-obstructive azoospermia (NOA) is a complex and severe condition whose etiology remains largely unknown. In a genome-wide association study (GWAS) of NOA in Chinese men, few loci reached genome-wide significance, although this might be a result of genetic heterogeneity. Single nucleotide polymorphisms (SNPs) without genome-wide significance may also indicate genes that are essential for fertility, and multiple stage validation can lead to false-negative results. To perform large-scale functional screening of the genes surrounding these SNPs, we used in vivo RNA interference (RNAi) in Drosophila, which has a short maturation cycle and is suitable for high-throughput analysis. The analysis found that 7 (31.8%) of the 22 analyzed orthologous Drosophila genes were essential for male fertility. These genes corresponded to nine loci. Of these genes, leukocyte-antigen-related-like (Lar) is primarily required in germ cells to sustain spermatogenesis, whereas CG12404, doublesex-Mab-related 11E (dmrt11E), CG6769, estrogen-related receptor (ERR) and sulfateless (sfl) function in somatic cells. Interestingly, ERR and sfl are also required for testis morphogenesis. Our study thus demonstrates that SNPs without genome-wide significance in GWAS may also provide clues to disease-related genes and therefore warrant functional analysis. |
| 巻・号 | 24(5) |
| ページ | 1493-503 |
| 公開日 | 2015-3-1 |
| DOI | 10.1093/hmg/ddu557 |
| PII | ddu557 |
| PMID | 25361961 |
| MeSH | Animals Asian People / genetics Azoospermia / genetics* Disease Models, Animal Drosophila / genetics* Drosophila Proteins / genetics Drosophila Proteins / metabolism Fertility / genetics* Genetic Association Studies Genetic Loci Genetic Predisposition to Disease Humans Male Polymorphism, Single Nucleotide RNA Interference Receptors, Estrogen / genetics Receptors, Estrogen / metabolism Spermatogenesis / genetics Sulfotransferases / genetics Sulfotransferases / metabolism Testis / metabolism |
| IF | 5.101 |
| 引用数 | 20 |
| WOS 分野 | GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY |
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| 各媒体での言及数の合計 | 0 |
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