Identification of seven genes essential for male fertility through a genome-wide association study of non-obstructive azoospermia and RNA interferencemediated large-scale functional screening in Drosophila

Jun Yu, Hao Wu, Yang Wen, Yujuan Liu, Tao Zhou, Bixian Ni, Yuan Lin, Jing Dong, Zuomin Zhou, Zhibin Hu, Xuejiang Guo, Jiahao Sha, Chao Tong

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18 Scopus citations


Non-obstructive azoospermia (NOA) is a complex and severe condition whose etiology remains largely unknown. In a genomewide 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, leukocyteantigen- 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 sflare 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.

Original languageEnglish (US)
Pages (from-to)1493-1503
Number of pages11
JournalHuman molecular genetics
Issue number5
StatePublished - Mar 1 2015


ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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