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 alters gene expression of the paternal allele‐specific protein‐coding genes and several maternal allel...

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Published in:Animal genetics Vol. 45; no. s1; pp. 51 - 61
Main Authors: Bidwell, C. A, Waddell, J. N, Taxis, T. M, Yu, H, Tellam, R. L, Neary, M. K, Cockett, N. E
Format: Journal Article
Language:English
Published: England Blackwell Science 01-08-2014
Blackwell Publishing Ltd
Wiley Subscription Services, Inc
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Summary: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 alters gene expression of the paternal allele‐specific protein‐coding genes and several maternal allele‐specific long noncoding RNA and microRNA when the mutation is inherited in cis. 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 on the paternal allele (+/C). We examined the changes of gene expression of four major transcripts from the DLK1–DIO3 cluster and four myosin isoforms during the development of muscle hypertrophy in the semimembranosus as well as in the supraspinatus that does not undergo hypertrophy. The homozygous (C/C) animals had an intermediate gene expression pattern for the paternal allele‐specific genes and two myosin isoforms, indicating a biological activity that was insufficient to change muscle mass. Transcriptome analysis was conducted by RNA sequencing in the four callipyge genotypes. The data show that homozygous animals (C/C) have lower levels of gene expression at many loci relative to the other three genotypes. A number of the downregulated genes are putative targets of the maternal allele‐specific microRNA with gene ontology, indicating regulatory and cell signaling functions. These results suggest that the trans‐effect of the maternal noncoding RNA and associated miRNA is to stabilize the expression of a number of regulatory genes at a functional, but low level to make the myofibers of homozygous (C/C) lambs less responsive to hypertrophic stimuli of the paternal allele‐specific genes.
Bibliography:http://dx.doi.org/10.1111/age.12132
ArticleID:AGE12132
USDA Cooperative State Research, Education, and Extension Service (National Research Initiative Grant) - No. 2005-35205-15589
ark:/67375/WNG-3HSZ9QWW-W
istex:E840509D775D6BA3187DCFB7790127EEC1CF1017
Purdue Agriculture Research Programs
Figure S1 Muscle growth in the four callipyge genotypes. Regression equations for muscle weight to live weight through 60 days of age were plotted for a) semimembranosus and b) supraspinatus. The semimembranosus has a significant increase in mass in callipyge (+/C) lambs relative to the other three genotypes. The supraspinatus does not become hypertrophied.Figure S2 Expression of genes from the DLK1-DIO3 region in the supraspinatus. Changes in gene expression from prenatal (-14 days pre-parturition) to 60 days of age are shown for a) DLK1; b) RTL1; c) MEG3 and d) MEG8. The absolute abundance was based on 100 ng input RNA using cloned amplicons as standards. The main effects and interaction statistics are shown above each graph.Figure S3 Expression of myosin genes in the supraspinatus. Changes in gene expression from prenatal (-14 days pre-parturition) to 60 days of age are shown for a) MYH2 (Type 2A); b) MYH4 (Type 2B) c) MYH7 (Type 1). The absolute abundance was based on 100 ng input RNA using cloned amplicons as standards. The main effects and interaction statistics are shown with each graph.Figure S4 Volcano plots for the pairwise comparisons of expression for microRNA target genes of the four callipyge genotypes. The data for 1041 genes that are predicted targets of miRNA from the DLK1-DIO3 region (Caiment et al. ) were extracted from the total dataset. The changes in gene level expression based on FPKM versus the FDR value were transformed as indicated on the axis. The pairwise genotype ratios for fold change calculations are indicated at the top of the panel and the numbers of differentially expressed genes are given at the upper right of each panel. Blue points above the significance threshold are not significant due to low read mapping counts.Table S1 Quantitative PCR primers for miRNA target genes. Table S2 Least Square Means and Standard Errors for qPCR. Table S3 Analysis of Muscle Growth by Live Weight using Linear Regression. Table S4A Main effects statistics for DLK1-DIO3 genes qPCR. Table S4B Main effects statistics for DLK1-DIO3 genes qPCR. Table S5 Interaction statistics for DLK1-DIO3 genes qPCR. Table S6 Main effects statistics for myosin genes qPCR.
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content type line 23
ISSN:0268-9146
1365-2052
DOI:10.1111/age.12132