New Insights into Polar Overdominance in Callipyge Sheep

The callipyge phenotype in sheep involves substantial postnatal muscle hypertrophy and other changes to carcass composition.  A single nucleotide polymorphism in the DLK1-DIO3 imprinted gene cluster has been identified as the cause of the callipyge trait. The callipyge SNP alters gene expression within the gene cluster when inherited in cis. The DLK1-DIO3 region in mammals includes two paternal-allele specific protein coding genes, several maternal allele-specific long noncoding RNA and a large number of maternal allele-specific microRNA. The inheritance pattern of the callipyge phenotype is polar overdominant because muscle hypertrophy only occurs in heterozygous animals that inherit a normal maternal allele and the callipyge SNP from paternal allele (+/C). The current model of polar overdominance involves cis and trans effects of the mutation on gene expression within the imprinted gene cluster. We have conducted RNA-seq analysis of gene expression in all four possible genotypes of the callipyge SNP in the semimembranosus muscle. The data shows that the homozygous animals (C/C) have lower levels of gene expression at many loci relative to the other three genotypes. A number of the down-regulated genes are putative targets of the maternal allele-specific microRNA. These results indicate that the trans effect of the callipyge mutation involves a number of genomic loci that inhibit muscle hypertrophy in homozygous (C/C) animals.