Breed composition but also because the flock in which it was detected was located very close to the Teagasc centre where the Belclare breed was developed and was also close to the Blindwell test farm where Teagasc evaluated a range breed crosses, including an extensive evaluation of Belclare and Belclarecross ewes during the 1980s. This conclusion is strengthened by the fact that follow-up discussions with the owner indicated the possibility that a Belclare x Galway type was among the ancestry of the ewe in question. The links between the Belclare and Cambridge breeds and the populations studied as possible sources of the mutations in BMP15 and GDF9 that are present in these two breeds are summarized in Fig. 2. The conclusions from the present work about the origin ofOrigins of BMP15 and GDF9 Mutations in SheepTable 4. Summary of sequence data for complete coding regions of BMP15 and GDF9 for animals of various genotypes at these loci and representing four breed groups.LocusGenotypeBreed groupNumber of SNPs other than those listed under genotype animals Carriers detected{ No. of homozygous carriers{ None None G2 (1), G3 (1), G7 (1) [haplotypes: G2G7] G2 (2), G3 (3), G4 (1) [haplotypes: G2G3, G3G4] G3 (1) None None NoneBMP+/+Cambridge Belclare Lleyn4 4 6 4 5 4 4 4 5 7 7 4 1 8 6 1 4None (4) None (4) None (4), B3 (2) None (4) None (5) None (3), B3 None (4) None (4) None (5) None (2), G2, G3 (4), G5 (2), G6 (4), G7 (5) G2 (3), G3 (7), G4 (3), G5, G6, G7 (3) None, G3 (3), G5, G6 G3 None (8) None (6) None None, G2, G3 (2), G4 GFecXG/FecXG FecXG/+ FecXB/FecXB FecXB/+ GDF9 +/+Cambridge Lleyn Belclare Lleyn Belclare HP Cambridge Belclare Lleyn HPFecGH/FecGHCambridge Belclare LleynFecG /+HLleyn HPNumber of cases given in parentheses where .1. Number of cases in parenthesis. doi:10.1371/journal.pone.0053172.t{{the various mutations are also shown. The mutations in BMP15 and GDF9 that are present in the Lleyn can explain the cases of ovarian hypoplasia reported by Vaughan et al. [32] in a flock of Lleyn sheep. The results from the Lleyn survey confirmed the presence of both FecXG and FecGH in the current Lleyn population; the carriers occurred Asiaticoside A cost throughout Britain and Ireland. No evidence was found for the presence in the Lleyn of any of the other known 24195657 mutations with large effect on fertility, from either MassArrayH iPLEX genotyping of rams for FecXB, FecXI, FecXH, FecXL and FecBB or from DNA sequencing of the BMP15 locus (15 ewes) and the GDF9 locus (9 ewes) spanning the coding regions encompassing the recently reported mutations FecXR [17]), FecGT [18] and FecGE [19], respectively. It remains unknown whether the unidentified mutations affecting ovarian function in Cambridge [33], Davisdale [34] and Lacaune sheep [35] are present in the Lleyn population. Since the discovery of mutations with a large effect on prolificacy the role of many these mutations in the prolificacy of other flocks has been examined in numerous studies. 11967625 However, the only mutations identified (to date) outside the breeds in which they were originally discovered are the FecBB mutation in the Indian Garole, Indonesian Javanese and the Small-tail Han and the Hu sheep of China [12,36], and the FecXG mutation in the Small-tail Han sheep [37]. Given the relatively large number of known mutations at the BMP15 locus it is seems PHCCC biological activity reasonable to suggest that the FecXG mutation in the Small-tail Han represents an independent mutation rather than reflecting some common origin with the Lley.Breed composition but also because the flock in which it was detected was located very close to the Teagasc centre where the Belclare breed was developed and was also close to the Blindwell test farm where Teagasc evaluated a range breed crosses, including an extensive evaluation of Belclare and Belclarecross ewes during the 1980s. This conclusion is strengthened by the fact that follow-up discussions with the owner indicated the possibility that a Belclare x Galway type was among the ancestry of the ewe in question. The links between the Belclare and Cambridge breeds and the populations studied as possible sources of the mutations in BMP15 and GDF9 that are present in these two breeds are summarized in Fig. 2. The conclusions from the present work about the origin ofOrigins of BMP15 and GDF9 Mutations in SheepTable 4. Summary of sequence data for complete coding regions of BMP15 and GDF9 for animals of various genotypes at these loci and representing four breed groups.LocusGenotypeBreed groupNumber of SNPs other than those listed under genotype animals Carriers detected{ No. of homozygous carriers{ None None G2 (1), G3 (1), G7 (1) [haplotypes: G2G7] G2 (2), G3 (3), G4 (1) [haplotypes: G2G3, G3G4] G3 (1) None None NoneBMP+/+Cambridge Belclare Lleyn4 4 6 4 5 4 4 4 5 7 7 4 1 8 6 1 4None (4) None (4) None (4), B3 (2) None (4) None (5) None (3), B3 None (4) None (4) None (5) None (2), G2, G3 (4), G5 (2), G6 (4), G7 (5) G2 (3), G3 (7), G4 (3), G5, G6, G7 (3) None, G3 (3), G5, G6 G3 None (8) None (6) None None, G2, G3 (2), G4 GFecXG/FecXG FecXG/+ FecXB/FecXB FecXB/+ GDF9 +/+Cambridge Lleyn Belclare Lleyn Belclare HP Cambridge Belclare Lleyn HPFecGH/FecGHCambridge Belclare LleynFecG /+HLleyn HPNumber of cases given in parentheses where .1. Number of cases in parenthesis. doi:10.1371/journal.pone.0053172.t{{the various mutations are also shown. The mutations in BMP15 and GDF9 that are present in the Lleyn can explain the cases of ovarian hypoplasia reported by Vaughan et al. [32] in a flock of Lleyn sheep. The results from the Lleyn survey confirmed the presence of both FecXG and FecGH in the current Lleyn population; the carriers occurred throughout Britain and Ireland. No evidence was found for the presence in the Lleyn of any of the other known 24195657 mutations with large effect on fertility, from either MassArrayH iPLEX genotyping of rams for FecXB, FecXI, FecXH, FecXL and FecBB or from DNA sequencing of the BMP15 locus (15 ewes) and the GDF9 locus (9 ewes) spanning the coding regions encompassing the recently reported mutations FecXR [17]), FecGT [18] and FecGE [19], respectively. It remains unknown whether the unidentified mutations affecting ovarian function in Cambridge [33], Davisdale [34] and Lacaune sheep [35] are present in the Lleyn population. Since the discovery of mutations with a large effect on prolificacy the role of many these mutations in the prolificacy of other flocks has been examined in numerous studies. 11967625 However, the only mutations identified (to date) outside the breeds in which they were originally discovered are the FecBB mutation in the Indian Garole, Indonesian Javanese and the Small-tail Han and the Hu sheep of China [12,36], and the FecXG mutation in the Small-tail Han sheep [37]. Given the relatively large number of known mutations at the BMP15 locus it is seems reasonable to suggest that the FecXG mutation in the Small-tail Han represents an independent mutation rather than reflecting some common origin with the Lley.