The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene

Genetic variations in ovulation rate which occur in different breeds of she ep provide useful models to explore the mechanisms regulating the developme nt of antral follicles. The Booroola gene, an autosomal mutation that affec ts ovulation rate, has been known for over two decades and despite intensiv e research it has riot yet been identified, Using resources from human geno me mapping and known data about gene linkage and chromosome location in the sheep, we selected the gene encoding the Bone Morphogenetic Protein recept or (BMPR) type 1 B (ALK-6) as a candidate site for the mutation. The BMPR1B gene in the human is located at the region linked with the Booroola mutati on, syntenic to chromosome 6 in the sheep. A fragment of the sheep BMPR1B g ene was cloned from an ovarian cDNA and the deduced aminoacid (AA) sequence is over 98% homologous to the known mammalian sequences. cDNA and genomic DNA from 20 Booroola genotypes were screened and two point mutation were fo und in the kinase domain of the receptor, one at base 746 of the coding reg ion (A in the ++ to a G in FF animals) which results in a change from a glu tamine in the wild type to a arginine in the Booroola animals. Another poin t mutation was identified at position 1113, (C to A) but this mutation does not change the coding aminoacid, Thr first mutation was confirmed in genom ic DNA from 10 ewes from an independent Brazilian flock which segregates th e Booroola phenotype. In all instances homozygous FecB gene carrier (n=11) had only the 746 A to G mutation, non gene carriers (n=14) had only the wil d type sequence and heterozygote gene carriers (n=5) had both sequences, Th is mutation in the subdomain 3 of the kinase domain could result in an alte ration in the expression and/or phosphorylation of SMADs, resulting in the phenotype characteristic of the Booroola animals which is the 'precocious' development of a large number of small antral follicles resulting in increa sed ovulation rate.