Gene set enrichment analysis using genome-wide association study to identify genes and pathways associated with litter size in various sheep breeds

The aim of this study was to identify the molecular pathways related to litter size in sheep using gene set enrichment analysis. For this purpose, information of high prolificacy sheep breeds including Wadi, Hu, Icelandic, Finnsheep, and Romanov and low prolificacy including Texel and Rahmani were used for genome wide association studies and gene set enrichment analysis. Genome-wide association study was conducted using GenABEL package of R program. Gene set enrichment analysis was performed with the goseq R package to identify the biological pathways associated with candidate genes. We identified different sets of candidate genes related to litter size: BMP5, DHCR24, BMPR1B, ESR1, ESR2 and PLCB1 in Wadi and Romanov; SMAD1, SMAD2, INSR and PTGS2 in Finnsheep and Hu; BMP7, NCOA1 and ERBB4 in Icelandic; BMP4, MSRB3 and SPP1 in Texel; BMP7, EGFR and KCNMA1 in Rahmani. According to pathway analysis, 30 pathways were associated with the litter size trait. Among biological pathways, the TGF-β signaling, Oxytocin signaling, Estrogen signaling, Prolactin signaling, and Insulin signaling pathways have significant association with ovulation rate and litter size trait. Overall, this study supported previous results from GWAS for litter size, also revealed additional regions in the sheep genome associated with litter size in sheep. These findings could potentially be useful for selective breeding for more litter size in sheep.