(Fec = Fecundity, B = Booroola) mutation plays a vital role in increasing ovulation rate and prolificacy in ewes. This mutation (c.746A>G) was in BMPR-IB
(Bone morphogenetic protein receptor IB) gene that located on chromosome 6,which was first found to be significantly associated with litter size in Booroola Merino ewes [1
(Bone morphogenetic protein 15) gene belongs to the TGFβ
(Transforming growth factor-β) family, which acts as a key regulator of granulosa cell (GC) processes in ovarian follicular development [4
]. The sheep BMP-15
gene is located on the X chromosome [4
]. The c.718C>T mutation (named FecXG
; Galway mutation) in BMP-15
gene was first identified in Cambridge and Belclare sheep, which increased ovulation rate and infertility [6
(Follicle stimulating hormone receptor) gene was first identified in rat Sertoli cells and may have an influence on the FSH (follicle stimulating hormone) signal transduction [7
]. Additionally, FSH has been reported to play an important role in the development of antral follicles [8
]. A variety of mutations were found in the 5' flanking region of ovine FSHR
gene, which were significantly associated with litter size in Australian sheep, Hu sheep and Small Tailed Han sheep [10
The Small Tailed Han sheep and Hu sheep were originally raised in Shandong Province and Jiangsu Province, China [13
]. They quickly gained the attention of Chinese sheep breeders and were largely used in the modern hybridization system as female parents because of their reputation for high fertility. To date, there are no reports about the combined effect of BMPR-IB
genes on litter size of Small Tailed Han sheep and Hu sheep. Therefore, the objectives of this study were to investigate the relationships of single nucleotide polymorphisms (SNPs) in BMPR-IB
, and their combined effect with litter size, which may serve as valuable markers for female fertility selection at the early stage in Small Tailed Han sheep and Hu sheep.
In the present study, we selected the ovine BMPR-IB
as candidate genes to analyze the effect of single-marker and multi-marker on litter size. The FecB
gene is crucial in the regulation of prolificacy phenotype in sheep [1
]. Several studies indicated that ewes carrying FecB
-mutation have significantly higher ovulation rates if compared with their wild-type contemporaries [1
]. In this study, the FecB
-mutation was found in Small Tailed Han sheep and Hu sheep, and was significantly associated with litter size, which is consistent with previous reports [15
gene plays a vital role in growth and differentiation of early ovarian follicles [19
]. In Inverdale and Hanna sheep, the c.718C>T mutation of the BMP-15
gene has been reported to show an increased ovulation rate under heterozygous conditions, and homozygotes are otherwise infertile [17
]. Chu et al.
(2005), Wang et al.
(2005) and Davis et al.
(2006) failed to detect the BMP-15
(FecXI) mutation in Hu sheep [17
], but a BMP-15
(FecXG) was identified in the Small Tailed Han Sheep by Chu et al.
]. In the present study, the BMP-15
(FecXG) mutation was detected in both Small Tailed Han and Hu sheep breeds. We also found that the c.718C>T mutation of the BMP-15
gene was significantly association with litter size, similar with previous studies in the Inverdale and Hanna sheep [17
]. Interestingly, there were no homozygotes (GG
genotype) detected in Small Tailed Han sheep (n
= 869) and Hu sheep (n
= 761). Chu et al.
also reported the absence of GG
genotype in Small Tailed Han sheep [15
]. There are two potential reasons for the lack of GG
genotype ewes in the population, one simple explanation is that GG
ewes did not exist in our population, another reason is that the GG
ewes may have existed in our population, but we selected the ewes with litter size records, and the infertile GG
ewes were excluded in this study. About 29% of ewes in the population are G+
genotype and mating occurred under a random model; we believe GG
genotype ewes should be generated under this model and therefore the GG
genotype ewes should be detected in the infertile group. Mating of the G+
genotype rams and G+
genotype ewes can help verify this speculation.
Numerous reports have shown that the FSHR
gene plays a key role in animal reproduction [25
]. Chu et al.
found two mutation (g.681T>C and g.629C>T) in the 5' flanking region of the FSHR
gene in Hu sheep and three novel mutations (g.200G>A, g.197G>A and g.98T>C) in Small Tail Han Sheep [12
]. In our previous study, a novel SNP (g.47C>T) was found in the 5' flanking region of the FSHR
gene in the Small Tailed Han sheep and Hu sheep [14
]. This SNP was significantly associated with litter size. Therefore, the ovine FSHR
gene could be selected as a candidate gene for improving litter size traits in sheep husbandry.
Interestingly, several groups have reported the multi-marker combination effect on litter size in sheep. Chu et al.
reported that the Small Tailed Han ewes carried BB/G+
) showed more litter size than those with either mutation alone [15
]. Individuals in Cambridge and Belclare breeds with mutations in both the GDF9
genes were found to be associated with greater ovulation rate than those with either single mutation [6
]. In the present study, mutations in both the BMPR-IB
genes were also detected in Hu sheep and Small Tailed Han sheep and we also found a third mutations (FSHR
g.47C>T) in these two breeds. The single marker-trait association analysis revealed that each mutation in ovine BMPR-IB
genes was significantly associated with litter size in this population, and multi-marker analysis showed that individuals with the BB/G+/CC
genotype had more lambs than those with only one predominant genotype, indicating that multiple markers may have a greater effect on contributing to the litter size in sheep and that the BB/G+/CC
genotype combinations of BMPR-IB
genes was considered as the superior genotype.