Toward Molecular Understanding of Polar Overdominance at the Ovine Callipyge Locus

callipyge phenotype (Gk calli-beautiful +-pyge buttocks) is a generalized muscular hypertrophy described in sheep. It is due to an increase in the size and proportion of fast twitch muscle fibers. It manifests itself only after birth at ~1 month of age. It exhibits a rostro-caudal gradient being more pronounced in the muscle of the pelvic limb and torso, hence its name. It is accompanied by a decrease in all measures of fatness. Affected animals are characterized by an improved feed efficiency and dressing percentage (for review, see Cockett et al. 2001). Quite logically, the callipyge phenotype initially caught the attention of animal breeders because of its potential agronomic value. Ensuing studies, however, would reveal some remarkable features of the callipyge phenotype, especially its non-Mendelian mode of inheritance. These would quickly attract more attention among the scientific community than its potential economic value, especially since the quality of callipyge meat appeared to be mediocre! The aim of this paper is to update and complement a recent review describing the present understanding of the genetics and epigenetics of the callipyge phenomenon (Georges et al. 2003). The callipyge phenotype was first reported in the 1980s, showing in ~15% of offspring of a Dorset ram called " Solid Gold. " When mated to wild-type ewes, cal-lipyge rams descending from Solid Gold produced 50% callipyge offspring, irrespective of sex. This Mendelian segregation ratio suggested that the callipyge phenotype results from an autosomal, nonrecessive mutation referred to as " CLPG " (Cockett et al. 1994). This mono-genic hypothesis was confirmed when the CLPG locus was mapped to a 4.5-cM marker interval on distal chro-Unexpectedly, crosses involving callipyge ewes and wild-type rams did not produce any callipyge offspring, despite the transmission of the CLPG-carrying chromosome from the mothers to half their offspring. This nonequivalence of reciprocal crosses suggested the involvement of a gene undergoing parental imprinting that would only be expressed from the paternal allele. This hypothesis was supported by the observation that nonex-pressing CLPG Mat /+ Pat rams would transmit the callipyge phenotype to their CLPG Pat-bearing offspring when mated to +/+ wild-type ewes. Parent-of-origin effects associated with uniparental disomies (UPDs) of the orthol-ogous 14q32 region in man (pUPD14; MIM #608149) and distal 12 region in the mouse (Georgiades et al. 2000) pointed toward the possible sharing of an imprinted locus in the three species. However, matings performed subsequently between callipyge ewes and rams, each known …