title: Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries).
abstract: Belclare and Cambridge are prolific sheep breeds, the origins of which involved selecting ewes with exceptionally high litter size records from commercial flocks. The variation in ovulation rate in both breeds is consistent with segregation of a gene (or genes) with a large effect on this trait. Sterile ewes, due to a failure of normal ovarian follicle development, occur in both breeds. New naturally occurring mutations in genes for the oocyte-derived growth factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are described. These mutations are associated with increased ovulation rate in heterozygous carriers and sterility in homozygous carriers in both breeds. This is the first time that a mutation in the gene for GDF9 has been found that causes increased ovulation rate and infertility in a manner similar to inactivating mutations in BMP15, and shows that GDF9 is essential for normal folliculogenesis in sheep. Furthermore, it is shown, for the first time in any species, that individuals with mutations in both GDF9 and BMP15 have a greater ovulation rate than sheep with either of the mutations separately.
authors: Teagasc, Research Centre, Athenry, County Galway, Ireland. shanrahan@athenry.teagasc.ie
authors: James P
authors: JP
authors: Hanrahan
authors: Scott M
authors: SM
authors: Gregan
authors: Philippe
authors: P
authors: Mulsant
authors: Michael
authors: M
authors: Mullen
authors: George H
authors: GH
authors: Davis
authors: Richard
authors: R
authors: Powell
authors: Susan M
authors: SM
authors: Galloway
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D000013:Congenital Abnormalities / Q000662:veterinary; D005260:Female; D005787:Gene Frequency; D055429:Growth Differentiation Factor 9; D006579:Heterozygote; D007247:Infertility, Female / Q000235:genetics / Q000662:veterinary*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D006080:Ovarian Follicle / Q000002:abnormalities*; D010060:Ovulation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics*; D013045:Species Specificity
chemical_list: D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins