| Summary: | <p>Abstract</p> <p>Background</p> <p>The callipyge mutation is located within an imprinted gene cluster on ovine chromosome 18. The callipyge trait exhibits polar overdominant inheritance due to the fact that only heterozygotes inheriting a mutant paternal allele (paternal heterozygotes) have a phenotype of muscle hypertrophy, reduced fat and a more compact skeleton. The mutation is a single A to G transition in an intergenic region that results in the increased expression of several genes within the imprinted cluster without changing their parent-of-origin allele-specific expression.</p> <p>Results</p> <p>There was a significant effect of genotype (p < 0.0001) on the transcript abundance of <it>DLK1, PEG11</it>, and <it>MEG8 </it>in the muscles of lambs with the callipyge allele. <it>DLK1 </it>and <it>PEG11 </it>transcript levels were elevated in the hypertrophied muscles of paternal heterozygous animals relative to animals of the other three genotypes. The <it>PEG11 </it>locus produces a single 6.5 kb transcript and two smaller antisense strand transcripts, referred to as <it>PEG11AS</it>, in skeletal muscle. <it>PEG11AS </it>transcripts were detectable over a 5.5 kb region beginning 1.2 kb upstream of the <it>PEG11 </it>start codon and spanning the entire open reading frame. Analysis of <it>PEG11 </it>expression by quantitative PCR shows a 200-fold induction in the hypertrophied muscles of paternal heterozygous animals and a 13-fold induction in homozygous callipyge animals. <it>PEG11 </it>transcripts were 14-fold more abundant than <it>PEG11AS </it>transcripts in the gluteus medius of paternal heterozygous animals. <it>PEG11AS </it>transcripts were expressed at higher levels than <it>PEG11 </it>transcripts in the gluteus medius of animals of the other three genotypes.</p> <p>Conclusions</p> <p>The effect of the callipyge mutation has been to alter the expression of <it>DLK1</it>, <it>GTL2</it>, <it>PEG11 </it>and <it>MEG8 </it>in the hypertrophied skeletal muscles. Transcript abundance of <it>DLK1 </it>and <it>PEG11 </it>was highest in paternal heterozygous animals and exhibited polar overdominant gene expression patterns; therefore, both genes are candidates for causing skeletal muscle hypertrophy. There was unique relationship of <it>PEG11 </it>and <it>PEG11AS </it>transcript abundance in the paternal heterozygous animals that suggests a RNA interference mechanism may have a role in <it>PEG11 </it>gene regulation and polar overdominance in callipyge sheep.</p>
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