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BOR - Papers in Press, published online ahead of print November 19, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.023093
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BIOLOGY OF REPRODUCTION 70, 900–909 (2004)
DOI: 10.1095/biolreprod.103.023093
© 2004 by the Society for the Study of Reproduction, Inc.


Ovary

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)1

James P. Hanrahan2,4, Scott M. Gregan5, Philippe Mulsant6, Michael Mullen7, George H. Davis8, Richard Powell3,7, and Susan M. Galloway5

Teagasc,4 Research Centre, Athenry, County Galway, Ireland AgResearch Molecular Biology Unit,5 Department of Biochemistry, University of Otago, Dunedin, New Zealand Insitut National de la Recherché Agronomique,6 Laboratoire de Genetique Cellulaire, Castanet-Tolosan, France Department of Microbiology,7 National University of Ireland, Galway, Ireland AgResearch Invermay Agricultural Centre,8 Mosgiel, New Zealand

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.

1 Supported, in part, by European Union Structural Funds (EAGGF) and by grants from the New Zealand Foundation for Research in Science and Technology.

2 Correspondence. FAX: 353 91 845847; shanrahan{at}athenry.teagasc.ie

3 Deceased




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