EXTENDING THE BOUNDARIES OF THE CALLIPYGE IMPRINTED GENE CLUSTER ON OVINE CHROMOSOME 18

¹ Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 4700 Old Main Hill, Logan, UT 84322-4700 USA

² Department of Genetics, Faculty of Veterinary Medicine, University of Liège, 20 Boulevard de Colonster (B43), 4000 - Liège, Belgium

³ Genoscope, Centre National de Séquençage, rue Gaston Crémieux, CP 5706, 91057 EVRY cedex, France

The callipyge trait in sheep has a unique mode of inheritance, termed "polar overdominance", in which only heterozygous individuals receiving the callipyge (CLPG) mutation from the sire exhibit the muscular hypertrophy phenotype. The molecular basis for callipyge polar overdominance presumably involves the interaction of multiple genes located in an imprinted gene cluster at the distal end of ovine chromosome 18. We previously described a core cluster of imprinted genes on ovine chromosome 18 (DLK1, GTL2, PEG11, and MEG8) whose expression is enhanced when the CLPG mutation is inherited in cis. In an attempt to define the chromosomal boundaries of this imprinted gene cluster, the present study was designed to identify and characterize the genes that flank the core cluster. In total, six genes were analyzed in this study, including five known genes (BEGAIN, DIO3, DIO3AS, WARS, and YY1) and one novel gene that was predicted from BAC sequences of chromosomal regions flanking the core cluster. Each gene was characterized by evaluating its expression in a panel of tissues from animals at multiple stages in development; determining its imprinting status; and assessing whether its expression is affected by the CLPG mutation. We demonstrate that BEGAIN is an imprinted, paternally expressed gene that defines the proximal boundary of the callipyge imprinted gene cluster. Transcript levels of BEGAIN and DIO3, a known imprinted gene located distal to the core cluster, were similar in animals of different callipyge genotypes, which indicates that the effect of the CLPG mutation is limited to the core cluster.