Ewes from the Booroola strain of Australian Mé rino sheep are characterized by high ovulation rate and litter size. This phenotype is due to the action of the FecB B allele of a major gene named FecB, as determined by statistical analysis of phenotypic data. By genetic analysis of 31 informative half-sib families from heterozygous sires, we showed that the FecB locus is situated in the region of ovine chromosome 6 corresponding to the human chromosome 4q22-23 that contains the bone morphogenetic protein receptor IB (BMPR-IB) gene encoding a member of the transforming growth factor-␤ (TGF-␤) receptor family. A nonconservative substitution (Q249R) in the BMPR-IB coding sequence was found to be associated fully with the hyperprolificacy phenotype of Booroola ewes. In vitro, ovarian granulosa cells from FecB B ͞FecB B ewes were less responsive than granulosa cells from FecB ؉ ͞FecB ؉ ewes to the inhibitory effect on steroidogenesis of GDF-5 and BMP-4, natural ligands of BMPR-IB. It is suggested that in FecB B ͞FecB B ewes, BMPR-IB would be inactivated partially, leading to an advanced differentiation of granulosa cells and an advanced maturation of ovulatory follicles.

No abstract

A total of 202 genes were cytogenetically mapped to goat chromosomes, multiplying by five the total number of regional gene localizations in domestic ruminants (255). This map encompasses 249 and 173 common anchor loci regularly spaced along human and murine chromosomes, respectively, which makes it possible to perform a genome-wide comparison between three mammalian orders. Twice as many rearrangements as revealed by ZOO-FISH were observed. The average size of conserved fragments could be estimated at 27 and 8 cm with humans and mice, respectively. The position of evolutionary breakpoints often correspond with human chromosome sites known to be vulnerable to rearrangement in neoplasia. Furthermore, 75 microsatellite markers, 30 of which were isolated from gene-containing bacterial artificial chromosomes (BACs), were added to the previous goat genetic map, achieving 88% genome coverage. Finally, 124 microsatellites were cytogenetically mapped, which made it possible to physically anchor and orient all the linkage groups. We believe that this comprehensive map will speed up positional cloning projects in domestic ruminants and clarify some aspects of mammalian chromosomal evolution.[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. G40978–G41020,AF083170–AF083184, AF088286, AF08287, AF083401–AF083406, AF082884, and AF082885.]

The association of polledness and intersexuality in domestic goats (PIS mutation) made them a practical genetic model for studying mammalian female-to-male sex reversal. In this study, gonads from XX sex-reversed goats (PIS-/-) were thoroughly characterized at the molecular and histologic level from the first steps of gonadal differentiation (36 days post coitum [dpc]) to birth. The first histologic signs of gonadal sex reversal were detectable between 36 and 40 dpc (4-5 days later than the XY male) and were mainly characterized by the reduction of the ovarian cortex and the organization of seminiferous cords. As early as 36 dpc, aromatase (CYP19) gene expression was decreased in XX (PIS-/-) gonads, whereas genes normally up-regulated in males, such as SOX9 and AMH, showed an increased expression level from 40 dpc. Thereafter, steroidogenic cell precursors were affected, and at 56 dpc, WNT4 and 3beta-HSD were expressed in a male-specific manner in sex-reversed gonads. Another noticeable feature was a progressive disappearance of germ cells, clearly visible in testicular cords around 70 dpc where 50-75% of germ cells were absent in XX (PIS-/-) gonads. These observations indicated that the causal mutation of PIS acts very early in the sex-determining cascade and affects primarily the supporting cells of the gonad.