Abstract
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.
Highlights
Flock profitability is greatly affected by ewe reproductive efficiency
We used Estimated breeding values (EBVs) as the response variable for genome-wide association study (GWAS) which can increase the power to some extent as we have a better estimate of the actual genetic variance
We applied the simpleM method for multiple testing correction. This approach can take into account the dependence among the single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium (LD) and a less stringent threshold can be applied
Summary
All the required information for this study was provided by the Department of Animal Science of Sari Agriculture Science and Natural Resource University (SANRU), Iran [1]. The phenotype dataset consisted of 3,848 birth records from 1,506 ewes that were collected from 2004 to 2012 at Abbas Abad Baluchi sheep Breeding Station, Iran. The pedigree file encompassed 4,727 animals with 178 sires, 1,509 dams, and 818 founders. A total of 91 of 1,506 ewes were genotyped by Illumina 50K SNP panel for 54,241 markers. A similar number of single- and twin-bearing ewes with minimum pedigree relationships to one another were selected for genotyping. These ewes had a total of 435 repeated records across six years
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