title: A 17 bp deletion in the Bone Morphogenetic Protein 15 (BMP15) gene is associated to increased prolificacy in the Rasa Aragonesa sheep breed.
abstract: Different mutations in the Bone Morphogenetic Protein 15 (BMP15) and the Growth Differentiation Factor 9 (GDF9) genes cause increased ovulation rate and infertility in a dosage-sensitive manner in sheep. They cause increased ovulation rate and twin and triplet births in heterozygotes, and complete primary ovarian failure in homozygotes resulting in total infertility. We are here presenting a novel mutation in the second exon of the ovine BMP15 gene, found in the Spanish breed Rasa Aragonesa. It consists of a 17 bp deletion resulting in displacement of the open reading frame and premature stop codons. As a consequence, nearly 85% of the sequence of the wild type aminoacidic chain in the second exon of the BMP15 pro-protein is modified or suppressed as only the first 45 amino acids are conserved of the 245 original. The mature peptide is lost. The ewes heterozygous for this deletion present very high prolificacy (2.66 lambs/birth) when compared to a mean flock prolificacy of 1.36 lambs. The deletion causes a complete lack of functionality of the second exon of BMP15, comparable to the effect of premature stop codons in other mutations. Therefore, homozygous females for the deletion are expected to present primary ovarian failure. DNA sequence analysis of the GDF9 coding regions detected only a synonymous Single Nucleotide Polymorphism (SNP), apparently not linked to changes in prolificacy.
authors.affiliation: Department of Anatomy, Embryology and Genetics, Faculty of Veterinary, University of Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain. monteagu@unizar.es
authors.forename: Luis V
authors.initials: LV
authors.lastname: Monteagudo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ponz
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Tejedor
authors.forename: Adolfo
authors.initials: A
authors.lastname: Laviña
authors.forename: Isidro
authors.initials: I
authors.lastname: Sierra
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005260:Female; D005298:Fertility / Q000235:genetics*; D016368:Frameshift Mutation; D017353:Gene Deletion; D055429:Growth Differentiation Factor 9 / Q000235:genetics; D008098:Litter Size; D008297:Male; D016133:Polymerase Chain Reaction / Q000662:veterinary; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D012756:Sheep / Q000235:genetics / Q000502:physiology*
chemical_list: D055430:Bone Morphogenetic Protein 15; D055429:Growth Differentiation Factor 9; D004247:DNA