Litter size, which is a complex economic trait in sheep, is affected by polygenes. Hu sheep are a prolific native breed in China and also an ideal resource for studying the genetic mechanism that controls litter size in sheep. In this study, we investigated the genetic effects of candidate genes on litter size in a large experimental population (n = 2021) of Hu sheep. A total of 23 single nucleotide polymorphisms (SNPs) including six reported major mutations (FecB, FecX, FecX, FecX, FecG, and FecG) and 17 novel SNPs in 10 candidate genes involved in reproduction were genotyped using KASPar technology. Genotyping showed that Hu sheep carry the FecB mutation, but not the FecX, FecX, FecX, FecG, and FecG mutations. Among the remaining 18 SNPs, 16 tagged SNPs were selected based on the HAPLOVIEW program. Analysis of single marker association indicated a significant association between litter size in Hu sheep and three mutations in the TGFβ superfamily (FecB, GDF9 and TGFBR2 genes). Quantitative trait modes (QTMs) analysis revealed that the FecB and GDF9 mutations exerted an additive effect, while the mutation located within TGFBR2 gene was dominant. Linear regression analysis of the association between multiple markers and litter size indicated a correlation between homozygous ewes with the GG/AA/TT genotype and larger litter size than any of the other genotypes. In conclusion, the FecB, GDF9, and TGFBR2 polymorphisms were implicated as genetic markers of potential importance in marker-assisted selection (MAS) strategies to improve litter size in Hu sheep.
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