A mutation creating a potential illegitimate microRNA target site in the myostat

[Guest guest]

Nat Genet. 2006 Jun 4

A mutation creating a potential illegitimate microRNA target site in

the myostatin gene affects muscularity in sheep.

Clop A, Marcq F, Takeda H, Pirottin D, Tordoir X, Bibe B, Bouix J,

Caiment F, Elsen JM, Eychenne F, Larzul C, Laville E, Meish F,

Milenkovic D, Tobin J, Charlier C, s M.

[1] Unit of Animal Genomics, Department of Animal Production, Faculty

of Veterinary Medicine & Centre for Biomedical Integrative

Genoproteomics, University of Liege (B43), 20 Boulevard de Colonster,

4000 Liege, Belgium. [2] These authors contributed equally to this

work.

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 x 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.