RRC ID |
32513
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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.
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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.
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ジャーナル |
Hum Mol Genet
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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.
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巻・号 |
24(5)
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ページ |
1493-503
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公開日 |
2015-3-1
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DOI |
10.1093/hmg/ddu557
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PII |
ddu557
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PMID |
25361961
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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
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引用数 |
20
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WOS 分野
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GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
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リソース情報 |
ショウジョウバエ |
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