Polymorphisms of the BMPR1B, BMP15 and GDF9 fecundity genes in four Chinese sheep breeds

Abstract

Numerous studies on prolific sheep breeds have shown that the transforming growth factor beta (TGF- $\beta$ ) superfamily members, including bone morphogenetic protein receptor type 1B (BMPR1B), bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), are the essential regulators of ovulation rate and litter size. In total, 11 known mutations (1 in BMPR1B, 6 in BMP15 and 4 in GDF9) are able to increase the ovulation rate and litter size, respectively. In this study, the genomic DNA was isolated from 512 high-prolificacy sheep (including the Small-tailed Han, Hu and Wadi sheep breeds) and 164 low-prolificacy sheep (Tan sheep), and genotyping of the specific mutations of the three fecundity-related genes was carried out by sequencing. The results showed that the FecB mutation in BMPR1B was detected in all four sheep breeds, and the frequency of B allele was significantly higher in the high-prolificacy breeds than that in the low-prolificacy breed ( $P<0.001$ ). A novel mutation, c.T755C (named S1), was found in BMP15 from the four sheep breeds. However, known mutations such as FecX ${}^I$ , FecX ${}^H$ , FecX ${}^B$ , FecX ${}^G$ , FecX ${}^L$ and FecX ${}^R$ were not detected in these breeds. Three known loci (G1, G3 and G4) and a new mutation, c.A1515G (named S2), were found in GDF9, and the other three known mutations (FecG ${}^H$ (G8), FecG ${}^E$ and FecTT) were not detected in all four sheep breeds. The genotype distribution at the G1 and G4 loci had significant differences between the low-prolificacy sheep breed and the other three high-prolificacy sheep breeds. There was no difference in the genotype distribution at the G1 and G4 loci between the three high-prolificacy sheep breeds. Haplotype analysis of the four polymorphic loci in GDF9 suggested that H4 (GGAA) was the preponderant haplotype in the three high-prolificacy sheep breeds, but H1 (GGGG) was in the low-prolificacy sheep breed. These results preliminarily showed that the BMPR1B and GDF9 might be major genes influencing the prolificacy of Chinese sheep breeds.

Figure 1

Sequence of genotypes $++$ , B $+$ and BB at the 746 loci in the Coding Sequence (CDS) region of BMPR1B sheep.

Figure 2

Sequence of genotypes CC, TC and TT at the 755 loci in the CDS region of sheep BMP15.

Figure 3

Sequence of genotypes of the G1, G3, G4 and S2 loci in the CDS region of sheep GDF9.

Figure 4

Linkage disequilibrium analyses in the G1, G3, G4 and S2 loci in sheep GDF9.