Abstract

Simple SummaryLitter size is one of the most important reproductive traits in sheep. Two single nucleotide polymorphisms (SNPs), g.71874104G>A and g.71833755T>C, in the Histone Cell Cycle Regulator (HIRA) gene, were identified by whole-genome sequencing (WGS) and may be correlated with litter size in sheep. The two SNPs were genotyped and expression patterns of HIRA was determined in sheep breeds with different fecundity and in groups of Small Tail Han sheep producing large or small litters. Association analysis indicated that both SNPs were significantly correlated with litter size in Small Tail Han sheep. Furthermore, high levels of HIRA expression may have a negative effect on litter size in Small Tail Han sheep.Maintenance of appropriate levels of fecundity is critical for efficient sheep production. Opportunities to increase sheep litter size include identifying single gene mutations with major effects on ovulation rate and litter size. Whole-genome sequencing (WGS) data of 89 Chinese domestic sheep from nine different geographical locations and ten Australian sheep were analyzed to detect new polymorphisms affecting litter size. Comparative genomic analysis of sheep with contrasting litter size detected a novel set of candidate genes. Two SNPs, g.71874104G>A and g.71833755T>C, were genotyped in 760 Small Tail Han sheep and analyzed for association with litter size. The two SNPs were significantly associated with litter size, being in strong linkage disequilibrium in the region 71.80–71.87 Mb. This haplotype block contains one gene that may affect litter size, Histone Cell Cycle Regulator (HIRA). HIRA mRNA levels in sheep with different lambing ability were significantly higher in ovaries of Small Tail Han sheep (high fecundity) than in Sunite sheep (low fecundity). Moreover, the expression levels of HIRA in eight tissues of uniparous Small Tail Han sheep were significantly higher than in multiparous Small Tail Han sheep (p < 0.05). HIRA SNPs significantly affect litter size in sheep and are useful as genetic markers for litter size.

Highlights

  • China has great diversity in its sheep resources

  • Whole-genome sequencing (WGS) revealed that 38,090,348 single nucleotide polymorphism (SNP) in total were screened and the windows with top five percent of values were considered as the significant threshold for single statistic

  • The selective sweep region (71.80–71.87 Mb) was under a slightly selection (ZFST = 7.05) which only includes Histone Cell Cycle Regulator (HIRA) gene, but there were no significant differences in ZH and ∆AF

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Summary

Introduction

China has great diversity in its sheep resources. Most indigenous Chinese sheep breeds are uniparous and only a few breeds have two or more offspring. Litter size is one of the most important reproductive traits in sheep, which is affected by genes with minor effects [1,2]. Whole-genome sequencing (WGS) is widely used to identify genetic variants underlying adaptive traits. By sequencing the genomes of individuals from representative populations many genetic variations contributing to phenotypic diversity in various species have been successfully characterized [3,4,5]. Population structure and genome selection among Chinese indigenous sheep breeds have been investigated using single nucleotide polymorphism (SNP) screening assays [6,7]

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