Two ovine BAC clones and a connecting long-range PCR product, jointly spanning ∼250 kb and representing most of the MULGE5-OY3 marker interval known to contain the clpg locus, were completely sequenced. The resulting genomic sequence was aligned with its human ortholog and extensively annotated. Six transcripts, four of which were novel, were predicted to originate from within the analyzed region and their existence confirmed experimentally: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8. RT-PCR experiments performed on a range of tissues sampled from an 8-wk-old animal demonstrated the preferential expression of all six transcripts in skeletal muscle, which suggests that they are under control of common regulatory elements. The six transcripts were also shown to be subject to parental imprinting: DLK1, DAT, and PEG11 were shown to be paternally expressed and GTL2, antiPEG11, and MEG8 to be maternally expressed.
The callipyge (CLPG) phenotype (from kappa(alpha)lambda(iota), "beautiful," and pi(iota)gamma(epsilon), "buttocks") described in sheep is an inherited muscular hypertrophy that is subject to an unusual parent-of-origin effect referred to as polar overdominance: only heterozygous individuals having inherited the CLPG mutation from their sire exhibit the muscular hypertrophy. The callipyge (clpg) locus was mapped to a chromosome segment of approximately 400 kb (refs. 2-4), which was shown to contain four genes (DLK1, GTL2, PEG11 and MEG8) that are preferentially expressed in skeletal muscle and subject to parental imprinting in this tissue. Here we describe the effect of the CLPG mutation on the expression of these four genes, and demonstrate that callipyge individuals have a unique expression profile that may account for the observed polar overdominance.
An inheritable muscular hypertrophy was recently described in sheep and shown to be determined by the callipyge gene mapped to ovine chromosome 18. Here, the callipyge phenotype was found to be characterized by a nonmendelian inheritance pattern, referred to as polar overdominance, where only heterozygous individuals having inherited the callipyge mutation from their sire express the phenotype. The possible role of parental imprinting in the determinism of polar overdominance is envisaged.
A mutation causi muscular hypertrophy, with associated leanness and improved feed efficiency, has been recently identified in domestic sheep (Ovis aries). Preliminary results indicate that an autosomal dominant gene may be responsible for this economically advantageous trait. We have exploited the conservation in sequence and chromosomal location of DNA markers across Bovidae to map the corresponding callipyge locus to ovine chromosome 18 using a battery of bovine chromosome 21 markers. Chromosomal localization of the ovine callipyge locus is the first step toward positional cloning of the corresponding gene.Increasingly, health concerns expressed by consumers determine the quality standards for meat. Currently, the fat content and lean composition of meat products are emphasized. In this work, we report the mapping of a gene affecting both the production efficiency and quality of meat in domestic sheep (Ovis aries). In 1983, a sheep producer identified a ram that possessed extreme muscling. The animal showed little external fat but had unusual muscling in its hind quarters. This phenotype was transmitted by the founder male to part of his offspring and to his descendants in later generations, suggesting an inheritable neomutation.Subsequently, a study was initiated to more rigorously determine the segregation mode ofthis muscular hypertrophy condition (1). In the study, 150 Rambouillet ewes with normal phenotypes were mated to rams that showed the muscular hypertrophy phenotype; the rams were themselves offspring of crosses between normal ewes and muscular hypertrophy males. Of the 200 lambs produced from the ewes, 97 (48.5%) expressed the muscular hypertrophy phenotype and segregation of the muscular hypertrophy phenotype was equal between the sexes. These data indicate a single autosomal gene is responsible for the muscular hypertrophy condition. The name callipyge (from Greek calli-, beautiful; -pyge buttocks) and symbol CLPG are proposed for this gene, and the existence of two alleles, CLPG and clpg, is suggested; CLPG/CLPG and CLPG/clpg animals are heavy muscled and clpg/clpg animals are conventional in appearance.Growth and carcass characteristics of animals expressing the callipyge trait were also analyzed in the study (2, 3). Birth weights, weaning weights, and rate of gain were not significantly different between the heavy muscled and normal phenotypes. However, muscle mass was 32.2% greater in lambs with muscular hypertrophy than in normal lambs. This increase in muscle mass was limited almost exclusively to the pelvic limb with little increase in the thoracic limb. Carcasses of heavy muscled animals were also remarkably lean, with 7.8% less fat than carcasses from normal animals.To characterize this potentially advantageous gene, we sought to identify genetic markers linked to the CLPG locus. As relatively few markers have been mapped in sheep, contrary to the situation in cattle, we exploited the conservation in sequence and chromosomal location of markers across Bovidae and used a battery ...
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