In other species: Japanese flounder , Mallard , rock pigeon , chicken , dog , pig , taurine cattle , goat , rabbit , pacu , water buffalo , Japanese quail , red seabream , yellow catfish

Categories: Muscle phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 601788 (gene) , 614160 (trait)

Links to relevant human diseases in MONDO:

• MONDO:0013598: myostatin-related muscle hypertrophy

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Disease-related: no

Key variant known: yes

Year key variant first reported: 2006

Cross-species summary: Abnormal increase in muscular tissue caused entirely by enlargement of existing cells (in contrast to muscular hyperplasia, in which the abnormal increase in muscular tissue is due to the formation and growth of new, normal muscle cells)

Species-specific description: Information presented here was previously listed under OMIA:001426-9940 Muscular hypertrophy (double muscling), Texel In addition to the occurrence of natural variants for this trait, variants have been created artificially: Genetically-modifed organism; GMO. For other forms of muscular hypertrophy in sheep see: OMIA 001355-9940:Muscular hypertrophy (double muscling), Carwell OMIA 001354-9940:Muscular hypertrophy (double muscling), Callipyge

Molecular basis: In uncovering a previously-unrecognised source of variation, Clop et al. (2006) reported : "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." GDF8 is now known as MSTN (myostatin), and the mutation is g+6223G>A; c.*1232G>A. Hu et al. (2013) showed that "Knockdown of myostatin expression by RNAi enhances muscle growth in transgenic sheep". Haynes et al. (2013) reported that "lambs homozygous for the MSTN g+6723G>A mutation have changes in carcass characteristics (dressing and total lean), organ weights, and muscle fiber number. This may be due to reduced myostatin protein early in utero, but after 4 wk of age there was no difference in the abundance of mature myostatin protein in muscle or plasma among MSTN A/A, MSTN A/G, and MSTN G/G genotypes."

Genetic engineering: Yes - in addition to the occurrence of natural variants, variants have been created artificially, e.g. by genetic engineering or gene editing
Have human generated variants been created, e.g. through genetic engineering and gene editing

Prevalence: Kijas et al. (2007) reported that the favourable allele (g+6723A) "is near fixation within Australian Texels and present in additional breeds including White Suffolk, Poll Dorset and Lincoln" and that the direction and size of allele effect was very similar to that in the original Belgian Texel report by Clop et al. (2006). Bignall et al. (2010) reported the same allele in East Friesian sheep. Han et al. (2013) reported 28 nucleotide substitutions within the MSTN gene in "a diverse range of sheep breeds including the New Zealand (NZ) Romney, Coopworth, Corriedale, Dorper, Perendale, Suffolk, Merino, Dorset Down, Poll Dorset, Texel and other NZ cross-bred sheep."

Breeds: Charollais (Sheep) (VBO_0001368), Lincoln Longwool (Sheep) (VBO_0001490), Poll Dorset (Sheep) (VBO_0001557), Texel (Sheep) (VBO_0001641), White Suffolk, Australia (Sheep) (VBO_0015632).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: