Gene set enrichment analysis using genome-wide association study to identify genes and biological pathways associated with twinning in Baluchi sheep

Baluchi sheep is one ofthe indigenous sheep breeds originating from the eastern part of Iran and it isadapted to the severe weather conditions. The economic efficiency of sheepbreeding is clearly related to the reproduction efficiency of the ewes. In thisstudy, twinning trait was studied as an important reproductive trait. Toidentify the genes associated with twinning trait, genome-wide association wasdone using 91 Baluchi ewes genotyped with 50k Illumina SNP chips. For thispurpose, the extended repeatability model was used. In the next step, a geneset enrichment analysis was implemented to identify the biological pathwaysassociated with the twinning. Six SNP markers on chromosomes 1, 3, 10, 15 and25 located in CTH, ANKRD13C, SRSF11, PTGER3, LDHB, LRRC40, and KCNMA1 geneswere identified. According to pathway analysis, 25 pathways were associatedwith the twinning trait. Among those pathways, the defense response biologicalpathway has an important role in the ovulation. Interferons and interleukinsare the main cytokine proteins in this pathway. These cytokines create aprocess such as inflammation that causes oocytes releasefrom the follicle into the oviductfor transport and fertilization. Cell adhesion andintercellular bridge pathways were other significant pathways. Cell junction pathwayvia the CX43 protein can affect the transfer of GDF9 effects togranulosa cells. To the best of our knowledge, this is the first study thatreports indirect effects of GDF9 on twinning trait in Iranian sheep.