Litter size is one of the most important economic traits in sheep. Identification of gene variants that are associated with the prolificacy rate is an important step in breeding program success and profitability of the farm. So, to identify genetic mechanisms underlying the variation in litter size in Iranian Baluchi sheep, a two-step genome-wide association study (GWAS) was performed. GWAS was conducted using genotype data from 91 Baluchi sheep. Estimated breeding values (EBVs) for litter size calculated for 3848 ewes and then used as the response variable. Besides, a pathway analysis using GO and KEGG databases were applied as a complementary approach. A total of three single nucleotide polymorphisms (SNPs) associated with litter size were identified, one each on OAR2, OAR10, and OAR25. The SNP on OAR2 is located within a novel putative candidate gene, Neurotrophic receptor tyrosine kinase 2. This gene product works as a receptor which is essential for follicular assembly, early follicular growth, and oocyte survival. The SNP on OAR25 is located within RAB4A which is involved in blood vessel formation and proliferation through angiogenesis. The SNP on OAR10 was not associated with any gene in the 1Mb span. Moreover, gene-set analysis using the KEGG database identified several pathways, such as Ovarian steroidogenesis, Steroid hormone biosynthesis, Calcium signaling pathway, and Chemokine signaling. Also, pathway analysis using the GO database revealed several functional terms, such as cellular carbohydrate metabolic, biological adhesion, cell adhesion, cell junction, and cell-cell adherens junction, among others. This is the first study that reports the NTRK2 gene affecting litter size in sheep and our study of this gene functions showed that this gene could be a good candidate for further analysis.

Ewe productivity is a composite and maternal trait that is considered the most important economic trait in sheep meat production. The objective of this study was the application of alternative genome-wide association study (GWAS) approaches followed by gene set enrichment analysis (GSEA) on the ewes’ genome to identify genes affecting pregnancy outcomes and lamb growth after parturition in Iranian Baluchi sheep. Three maternal composite traits at birth and weaning were considered. The traits were progeny birth weight, litter mean weight at birth, total litter weight at birth, progeny weaning weight, litter mean weight at weaning, and total litter weight at weaning. GWASs were performed on original phenotypes as well as on estimated breeding values. The significant SNPs associated with composite traits at birth were located within or near genes RDX, FDX1, ARHGAP20, ZC3H12C, THBS1, and EPG5. Identified genes and pathways have functions related to pregnancy, such as autophagy in the placenta, progesterone production by the placenta, placental formation, calcium ion transport, and maternal immune response. For composite traits at weaning, genes (NR2C1, VEZT, HSD17B4, RSU1, CUBN, VIM, PRLR, and FTH1) and pathways affecting feed intake and food conservation, development of mammary glands cytoskeleton structure, and production of milk components like fatty acids, proteins, and vitamin B-12, were identified. The results show that calcium ion transport during pregnancy and feeding lambs by milk after parturition can have the greatest impact on weight gain as compared to other effects of maternal origin.

BackgroundLitter size and ovulation rate are important reproduction traits in sheep and have important impacts on the pro tability of farm animals. To investigate the genetic architecture of litter size, we report the rst meta-analysis of genome-wide association studies (GWAS) using 522 ewes and 564,377 SNPs from six sheep breeds. ResultsWe identi ed 29 signi cant associations for litter size which 27 of which have been not reported in GWASs for each population. However, we could con rm the role of BMPR1B in proli cacy. Our gene set analysis discovered biological pathways related to cell signaling, communication, and adhesion.Functional clustering and enrichment using protein databases identi ed epidermal growth factor-like domain affecting litter size. Through analyzing protein-protein interaction data, we could identify hub genes like CASK, PLCB4, RPTOR, GRIA2, and PLCB1 that were enriched in most of the signi cant pathways. These genes have a role in cell proliferation, cell adhesion, cell growth and survival, and autophagy. ConclusionsNotably, identi ed SNPs were scattered on several different chromosomes implying different genetic mechanisms underlying variation of proli cacy in each breed. Given the different layers that make up the follicles and the need for communication and transfer of hormones and nutrients through these layers to the oocyte, the signi cance of pathways related to cell signaling and communication seems logical. Our results provide genetic insights into the litter size variation in different sheep breeds.

Background Litter size and ovulation rate are important reproduction traits in sheep and have important impacts on the profitability of farm animals. To investigate the genetic architecture of litter size, we report the first meta-analysis of genome-wide association studies (GWAS) using 522 ewes and 564,377 SNPs from six sheep breeds. Results We identified 29 significant associations for litter size which 27 of which have been not reported in GWASs for each population. However, we could confirm the role of BMPR1B in prolificacy. Our gene set analysis discovered biological pathways related to cell signaling, communication, and adhesion. Functional clustering and enrichment using protein databases identified epidermal growth factor-like domain affecting litter size. Through analyzing protein-protein interaction data, we could identify hub genes like CASK, PLCB4, RPTOR, GRIA2, and PLCB1 that were enriched in most of the significant pathways. These genes have a role in cell proliferation, cell adhesion, cell growth and survival, and autophagy. Conclusions Notably, identified SNPs were scattered on several different chromosomes implying different genetic mechanisms underlying variation of prolificacy in each breed. Given the different layers that make up the follicles and the need for communication and transfer of hormones and nutrients through these layers to the oocyte, the significance of pathways related to cell signaling and communication seems logical. Our results provide genetic insights into the litter size variation in different sheep breeds.

Background Ewe productivity is considered as the most important economic trait in sheep meat production. Due to very limited reports, the objective of this study was the application of alternative GWAS approaches followed by gene set enrichment analysis (GSEA) on the maternal genome to unravel the genomic architecture underlying ewe productivity in Iranian Baluchi sheep. Six maternal composite traits including progeny birth weight (PBW), litter mean weight at birth (LMWB), total litter weight at birth (TLWB), progeny weaning weight (PWW), litter mean weight at weaning (LMWW) and total litter weight at weaning (TLWW) were studied. Results Genes such as RDX , FDX1 , ARHGAP20 , ZC3H12C , THBS1 , and EPG5 on OAR6, OAR7, OAR15, and OAR23 were identified for composite traits at birth. The genes are involved in pregnancy, including autophagy in the placenta, progesterone production by the placenta, maternal immune response and placenta formation. Some maternal pathways, related to calcium ion transport, signal transduction, neurogenesis, and immune response were also identified for birth weight traits. Moreover, many genes including NR2C1 , VEZT , HSD17B4 , RSU1 , CUBN , VIM , PRLR , and FTH1 were located on OAR2, OAR3, OAR5, OAR7, OAR13, OAR16, and OAR25 identified as maternal genes affecting weaning weight traits. Most of the identified genes were involved in mammary glands development and milk components production. Also, many GO terms related to protein processing and transport, ion transport and homeostasis, proteins and lipid phosphorylation, and phospholipid translocation were identified in association with weaning weight traits. Conclusions The results of the present study revealed that calcium ion homeostasis and transport and the maternal immune system could have an important role in progeny’s birth weight. Also, the results showed that genes and pathways affecting mammary glands development during pregnancy and milk components production have the most impact on lambs weaning weight. These findings contribute to a better understanding of the genetic architecture of the studied traits and providing opportunities for improving ewe productivity via marker-assisted selection.