Identification of CCSER1 missense variants and diplotypes as molecular markers for growth and lambing-related traits in Junken meat sheep

Abstract

To validate the potential role of CCSER1, a candidate gene for litter size and yearling weight identified by selection signature analysis, in lambing performance and growth development of Junken meat sheep, CCSER1 polymorphisms were genotyped using the Sequenom MassARRAY® SNP assay. Association analysis was conducted to assess the associations of CCSER1 polymorphisms and SNP2–SNP3 diplotypes with growth and lambing-related traits, and reverse transcription quantitative PCR (RT-qPCR) was used to determine the expression profile of CCSER1 in the ewes' digestive, developmental and reproductive tissues. The results showed three missense mutations in the CCSER1 gene of Junken meat sheep were identified, including SNP1 (XM_042251242.2: c.2557C>T) in exon 11, SNP2 (XM_042251242.2: c.1206A>G) and SNP3 (XM_042251242.2: c.16T>C) in exon 2. Three SNPs were exploratorily predicted to alter the secondary and tertiary structures of the CCSER1 protein. A single-stage mixed model was applied to evaluate the associations between individual SNP genotypes and phenotypic variation, with Bonferroni correction subsequently performed for multiple testing within each trait. The results showed that the associations of SNP2 with ABW (adjusted P = 0.0024) and SNP3 with YW (adjusted P = 0.022) and ADG2 (adjusted P = 0.039) remained statistically significant after Bonferroni correction. Phasing analysis of SNP2 and SNP3 identified four chromosome-level haplotypes and six corresponding diplotypes. A significant diplotype association was observed for YW (adjusted P = 0.039). Tukey's HSD test indicated that individuals carrying the T-A/T-A or T-A/T-G diplotypes exhibited significantly higher YW compared with those carryingT-G/T-G diplotype. The RT-qPCR analysis revealed a tissue-specific expression profile of CCSER1, with the highest expression detected in the abomasum (P < 0.01). In addition, CCSER1 expression levels in the lung and ovary were significantly higher than those in the liver, kidney, skin, brain, and pituitary gland (P < 0.01). These findings suggest that CCSER1 is a candidate gene for growth and lambing-related traits in Junken meat sheep, and that SNP2, SNP3, T-A/T-A and T-A/T-G may serve as useful molecular markers for marker-assisted selection to improve lambing performance and growth development in sheep.