A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep

• Published in: Nature genetics Vol. 38; no. 7; pp. 813 - 818
• Main Authors: Eychenne, Francis, Tordoir, Xavier, Georges, Michel, Clop, Alex, Bouix, Jacques, Bibé, Bernard, Caiment, Florian, Meish, Françoise, Marcq, Fabienne, Laville, Elisabeth, Tobin, James, Pirottin, Dimitri, Elsen, Jean-Michel, Charlier, Carole, Takeda, Haruko, Larzul, Catherine, Milenkovic, Dragan
• Format: Journal Article Web Resource
• Language: English
• Published: London Nature Publishing Group 01.07.2006
• Subjects: Animals; Binding Sites - genetics; Biological and medical sciences; Chromosome Mapping; Fundamental and applied biological sciences. Psychology; Gene expression; Gene loci; Gene mutations; Genetic aspects; Genetics; Genetics & genetic processes; Genetics of eukaryotes. Biological and molecular evolution; Genomics; Génétique & processus génétiques; Humans; Hypertrophy; Life Sciences; Mice; MicroRNAs - genetics; Muscle diseases; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal/metabolism/pathology; Muscular system; Mutation; Myostatin; Médecine vétérinaire & santé animale; Physiological aspects; Polymorphism, Single Nucleotide; Proteins; Quantitative Trait Loci; Ribonucleic acid; Risk factors; RNA; Sciences du vivant; Sheep; Sheep - anatomy & histology; Sheep - genetics; Sheep/anatomy & histology/genetics; Transforming Growth Factor beta - genetics; Veterinary medicine & animal health; United States; Gene silencing; Vertebrata; Mammalia; Gene; Sheep; Artiodactyla; Mutation; Ungulata; HYPERTROPHY; MUSCULARITY; SNP; TEXEL SHEEP; MYOSTATIN GENE; GDF8
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng1810

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov × Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3′ UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation.