Submitted September 18, 2003
Returned for revision October 20, 2003
Accepted November 18, 2003
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)
James P. Hanrahan *,
Scott M. Gregan ,
Philippe Mulsant ,
Michael Mullen ,
George H. Davis ,
Richard Powell ,
and
Susan M. Galloway
* To whom correspondence should be addressed. E-mail: shanrahan{at}athenry.teagasc.ie.
Abstract
Belclare and Cambridge are prolific sheep breeds whose
origins 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 GDF9 and 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.
Key words:
Ovary •
Follicle •
Follicular development •
Growth factors •
Ovulation
