Hum Mol Genet. 2015 Mar 1;24(5):1493-503.
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.
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. 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, Lar is primarily required in germ cells to sustain spermatogenesis, whereas CG12404, dmrt11E, CG6769, ERR, and 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.
