Utilization of fecundity genes such as GDF9 and BMP15 can help improve reproductive traits in sheep breeding programme. To evaluate effects of missense mutations on protein function, the polymorphisms of GDF9 and BMP15 genes were screened in twelve mehraban sheep using DNA sequencing, followed by protein structure modeling. Six single nucleotide polymorphism (SNPs) known as FecG mutations (G1-G6), were detected in exons 1 and 2 of GDF9 gene. Mutations of G1 (GDF9 exon 1 g.2118 G>A), G4 (GDF9 exon 2 g.3451 T>C) and G6 (GDF9 exon 2 g.3974 G>A) have shown amino acid substitution. None polymorphism was detected in exon 1 and exon 2 of BMP15 gene. Based on identified polymor-phisms, individuals were classified into three haplotypes of wild haplotype (without mutation), haplotype A (simultaneous mutations of G1, G2, G3 and G4) and haplotype B (simultaneous mutations of G5 and G6). The 3D-structure of GDF9 protein in A and B haplotypes was rotated 90° and 45° than wild haplotype, re-spectively. The missenses G1/p.Arg87His, G4/p.Glu241Lys and G6/p.Val332Ile variants were benign. However both the missenses of G7/p.Val371Met and G8/p.Ser315Phe were probably damaging. Phyloge-netic tree of GDF9 gene revealed that individuals with A and B haplotypes were distinct from wild haplo-types with bootstrapping values of 63 and 76, respectively. In conclusion, GDF9 protein in A and B haplo-types showed a higher performance than wild haplotype due to synergism effects of simultaneous muta-tions. These types of mutations with effect on turn and helix of GDF9 conservative regions showed physi-cal and functional interaction with TGFβ proteins.
