Abstract
BackgroundThe 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.ResultsThere was a significant effect of genotype (p < 0.0001) on the transcript abundance of DLK1, PEG11, and MEG8 in the muscles of lambs with the callipyge allele. DLK1 and PEG11 transcript levels were elevated in the hypertrophied muscles of paternal heterozygous animals relative to animals of the other three genotypes. The PEG11 locus produces a single 6.5 kb transcript and two smaller antisense strand transcripts, referred to as PEG11AS, in skeletal muscle. PEG11AS transcripts were detectable over a 5.5 kb region beginning 1.2 kb upstream of the PEG11 start codon and spanning the entire open reading frame. Analysis of PEG11 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. PEG11 transcripts were 14-fold more abundant than PEG11AS transcripts in the gluteus medius of paternal heterozygous animals. PEG11AS transcripts were expressed at higher levels than PEG11 transcripts in the gluteus medius of animals of the other three genotypes.ConclusionsThe effect of the callipyge mutation has been to alter the expression of DLK1, GTL2, PEG11 and MEG8 in the hypertrophied skeletal muscles. Transcript abundance of DLK1 and PEG11 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 PEG11 and PEG11AS transcript abundance in the paternal heterozygous animals that suggests a RNA interference mechanism may have a role in PEG11 gene regulation and polar overdominance in callipyge sheep.
Highlights
The callipyge mutation is located within an imprinted gene cluster on ovine chromosome 18
Northern blot analysis Muscle samples were collected from 12- and 8-week-old lambs, when muscle hypertrophy is well established in animals with the callipyge phenotype
Total RNA was extracted from three muscles that undergo hypertrophy including longissimus dorsi, semimembranosus, and gluteus medius, and one muscle that does not undergo hypertrophy, the supraspinatus
Summary
The callipyge mutation is located within an imprinted gene cluster on ovine chromosome 18. The mutation responsible for the callipyge trait is located within an imprinted gene cluster on the distal end of ovine chromosome 18 [1,2,3]. DAT is a short non-coding RNA that has been proposed to be a cleavage product of extended DLK1 transcripts [21]. Both DLK1and DAT are expressed from the paternal allele [3,13,14,15]. GTL2 ( referred to as MEG3) and MEG8 genes express non-coding RNA from the maternal allele [3,13,14,15]. Two maternally expressed microRNAs have been identified with perfect complementarity to mouse Rtl1 [22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
