Tuesday, November 17, 2015

Using the fly to identify new human genes associated with disorders, even when the GWAS stats are shaky

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. 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. Hum Mol Genet. 2015 Mar 1;24(5):1493-503. PMID: 25361961.

From the abstract: "Non-obstructive azoospermia (NOA) is a complex and severe condition ... In a genome-wide association study (GWAS) of NOA in Chinese men, few loci reached genome-wide significance ... 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 ... 7 (31.8%) of the 22 analyzed orthologous Drosophila genes were essential for male fertility. ... 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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