OMIA 001426-9940 : Muscular hypertrophy (double muscling), Texel in Ovis aries

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2006

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."

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."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MSTN myostatin Ovis aries 2 NC_019459.2 (118140420..118145410) MSTN Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Texel Muscular hypertrophy (double muscling), Texel MSTN regulatory g+6223G>A c.*1232G>A "G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs)" 2006 16751773

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2018 Aiello, D., Patel, K., Lasagna, E. :
The myostatin gene: an overview of mechanisms of action and its relevance to livestock animals. Anim Genet :, 2018. Pubmed reference: 30125951. DOI: 10.1111/age.12696.
Freking, B.A., King, D.A., Shackelford, S.D., Wheeler, T.L., Smith, T.P.L. :
Effects and interactions of myostatin and callipyge mutations: I. Growth and carcass traits. J Anim Sci 96:454-461, 2018. Pubmed reference: 29401324. DOI: 10.1093/jas/skx055.
2016 Li, H., Wang, G., Hao, Z., Zhang, G., Qing, Y., Liu, S., Qing, L., Pan, W., Chen, L., Liu, G., Zhao, R., Jia, B., Zeng, L., Guo, J., Zhao, L., Zhao, H., Lv, C., Xu, K., Cheng, W., Li, H., Zhao, H.Y., Wang, W., Wei, H.J. :
Generation of biallelic knock-out sheep via gene-editing and somatic cell nuclear transfer. Sci Rep 6:33675, 2016. Pubmed reference: 27654750. DOI: 10.1038/srep33675.
Wang, X., Niu, Y., Zhou, J., Yu, H., Kou, Q., Lei, A., Zhao, X., Yan, H., Cai, B., Shen, Q., Zhou, S., Zhu, H., Zhou, G., Niu, W., Hua, J., Jiang, Y., Huang, X., Ma, B., Chen, Y. :
Multiplex gene editing via CRISPR/Cas9 exhibits desirable muscle hypertrophy without detectable off-target effects in sheep. Sci Rep 6:32271, 2016. Pubmed reference: 27562433. DOI: 10.1038/srep32271.
2013 Han, J., Forrest, R.H., Hickford, J.G. :
Genetic variations in the myostatin gene (MSTN) in New Zealand sheep breeds. Mol Biol Rep :, 2013. Pubmed reference: 24081623. DOI: 10.1007/s11033-013-2752-7.
Haynes, F.E., Greenwood, P.L., McDonagh, M.B., McMahon, C.D., Nicholas, G.D., Berry, C.J., Oddy, V.H. :
Lack of association between allelic status and myostatin content in lambs with the myostatin g+6723G>A allele. J Anim Sci 91:78-89, 2013. Pubmed reference: 23048142. DOI: 10.2527/jas.2012-5482.
Hu, S., Ni, W., Sai, W., Zi, H., Qiao, J., Wang, P., Sheng, J., Chen, C. :
Knockdown of myostatin expression by RNAi enhances muscle growth in transgenic sheep. PLoS One 8:e58521, 2013. Pubmed reference: 23526994. DOI: 10.1371/journal.pone.0058521.
Liu, C., Li, W., Zhang, X., Zhang, N., He, S., Huang, J., Ge, Y., Liu, M. :
Knockdown of endogenous myostatin promotes sheep myoblast proliferation. In Vitro Cell Dev Biol Anim :, 2013. Pubmed reference: 24052475. DOI: 10.1007/s11626-013-9689-y.
Zhang, C., Wang, L., Ren, G., Li, Z., Ren, C., Zhang, T., Xu, K., Zhang, Z. :
Targeted disruption of the sheep MSTN gene by engineered zinc-finger nucleases. Mol Biol Rep :, 2013. Pubmed reference: 24197697. DOI: 10.1007/s11033-013-2853-3.
2012 Haynes, F.E., Greenwood, P.L., McDonagh, M.B., Oddy, V.H. :
Myostatin allelic status interacts with level of nutrition to affect growth, composition, and myofiber characteristics of lambs. J Anim Sci 90:456-65, 2012. Pubmed reference: 21926323. DOI: 10.2527/jas.2011-4452.
Liu, C., Li, W., Zhang, X., Zhang, N., He, S., Huang, J., Ge, Y., Liu, M. :
The critical role of myostatin in differentiation of sheep myoblasts. Biochem Biophys Res Commun 422:381-6, 2012. Pubmed reference: 22580276. DOI: 10.1016/j.bbrc.2012.04.151.
Lu, J., Sun, D., Xu, L., Lu, G., Zhao, F., Wei, C., Zhang, L., Ding, J., Li, B., Du, L. :
Selection of an effective small interference RNA to silence myostatin gene expression in sheep fibroblast cells. Biochem Genet 50:838-47, 2012. Pubmed reference: 22736258. DOI: 10.1007/s10528-012-9524-2.
Tang, D., Zhu, H., Wu, J., Chen, H., Zhang, Y., Zhao, X., Chen, X., Du, W., Wang, D., Lin, X. :
Silencing myostatin gene by RNAi in sheep embryos. J Biotechnol 158:69-74, 2012. Pubmed reference: 22285957. DOI: 10.1016/j.jbiotec.2012.01.008.
Tellam, R.L., Cockett, N.E., Vuocolo, T., Bidwell, C.A. :
Genes contributing to genetic variation of muscling in sheep. Front Genet 3:164, 2012. Pubmed reference: 22952470. DOI: 10.3389/fgene.2012.00164.
2011 Boman, I.A., Klemetsdal, G., Nafstad, O., Blichfeldt, T., Våge, D.I. :
Selection based on progeny testing induces rapid changes in myostatin allele frequencies - a case study in sheep. J Anim Breed Genet 128:52-5, 2011. Pubmed reference: 21214644. DOI: 10.1111/j.1439-0388.2010.00879.x.
Sjakste, T., Paramonova, N., Grislis, Z., Trapina, I., Kairisa, D. :
Analysis of the single-nucleotide polymorphism in the 5'UTR and part of intron I of the sheep MSTN gene. DNA Cell Biol 30:433-44, 2011. Pubmed reference: 21323579. DOI: 10.1089/dna.2010.1153.
2010 Bignell, C.W., Malau-Aduli, A.E., Nichols, P.D., McCulloch, R., Kijas, J.W. :
East Friesian sheep carry a Myostatin allele known to cause muscle hypertrophy in other breeds. Anim Genet 41:445-6, 2010. Pubmed reference: 20219067. DOI: 10.1111/j.1365-2052.2010.02021.x.
Boman, I.A., Klemetsdal, G., Nafstad, O., Blichfeldt, T., Våge, D.I. :
Impact of two myostatin (MSTN) mutations on weight gain and lamb carcass classification in Norwegian White Sheep (Ovis aries). Genet Sel Evol 42:4, 2010. Pubmed reference: 20113462. DOI: 10.1186/1297-9686-42-4.
Braunschweig, M.H. :
Mutations in the bovine ABCG2 and the ovine MSTN gene added to the few quantitative trait nucleotides identified in farm animals: a mini-review. J Appl Genet 51:289-97, 2010. Pubmed reference: 20720303. DOI: 10.1007/BF03208858.
Hickford, J.G., Forrest, R.H., Zhou, H., Fang, Q., Han, J., Frampton, C.M., Horrell, A.L. :
Polymorphisms in the ovine myostatin gene (MSTN) and their association with growth and carcass traits in New Zealand Romney sheep. Anim Genet 41:64-72, 2010. Pubmed reference: 19799595. DOI: 10.1111/j.1365-2052.2009.01965.x.
Takeda, H., Charlier, C., Farnir, F., Georges, M. :
Demonstrating polymorphic miRNA-mediated gene regulation in vivo: application to the g+6223G->A mutation of Texel sheep. RNA 16:1854-63, 2010. Pubmed reference: 20679369. DOI: 10.1261/rna.2131110.
2009 Boman, I.A., Klemetsdal, G., Blichfeldt, T., Nafstad, O., Våge, D.I. :
A frameshift mutation in the coding region of the myostatin gene (MSTN) affects carcass conformation and fatness in Norwegian White Sheep (Ovis aries). Anim Genet 40:418-22, 2009. Pubmed reference: 19392824. DOI: 10.1111/j.1365-2052.2009.01855.x.
Boman, I.A., Våge, D.I. :
An insertion in the coding region of the myostatin (MSTN) gene affects carcass conformation and fatness in the Norwegian Spaelsau (Ovis aries). BMC Res Notes 2:98, 2009. Pubmed reference: 19505313. DOI: 10.1186/1756-0500-2-98.
Gong, Y.F., Li, X.L., Liu, Z.Z., Jin, X.M., Zhou, R.Y., Li, L.H., Zhang, Q. :
SNP detection and haplotype analysis in partial sequence of MSTN gene in sheep. Genetika 45:1646-9, 2009. Pubmed reference: 20198976.
Hickford, J.G., Forrest, R.H., Zhou, H. :
Association between a g.+6723G-A SNP in the myostatin gene (MSTN) and carcass traits in New Zealand Texel sheep. J Anim Sci 87:1853, 2009. Pubmed reference: 19443859. DOI: 10.2527/jas.2009-1960.
Johnson, P.L., Dodds, K.G., Bain, W.E., Greer, G.J., McLean, N.J., McLaren, R.J., Galloway, S.M., van Stijn, T.C., McEwan, J.C. :
Investigations into the GDF8 g+6723G-A polymorphism in New Zealand Texel sheep. J Anim Sci 87:1856-64, 2009. Pubmed reference: 19251921. DOI: 10.2527/jas.2008-1508.
2008 Hadjipavlou, G., Matika, O., Clop, A., Bishop, S.C. :
Two single nucleotide polymorphisms in the myostatin (GDF8) gene have significant association with muscle depth of commercial Charollais sheep. Anim Genet 39:346-53, 2008. Pubmed reference: 18462481. DOI: 10.1111/j.1365-2052.2008.01734.x.
Meng, X.R., Guo, J., Zhao, Q.J., Ma, Y.H., Guan, W.J., Liu, D., Di, R., Qiao, H.Y., Na, R.S. :
[Variation of MSTN gene UTR in eleven sheep breeds]. Yi Chuan 30:1585-90, 2008. Pubmed reference: 19073574.
Rodgers, B.D., Garikipati, D.K. :
Clinical, agricultural, and evolutionary biology of myostatin: a comparative review. Endocr Rev 29:513-34, 2008. Pubmed reference: 18591260. DOI: 10.1210/er.2008-0003.
Zhou, H., Hickford, J.G., Fang, Q. :
Variation in the coding region of the myostatin (GDF8) gene in sheep. Mol Cell Probes 22:67-8, 2008. Pubmed reference: 17935943. DOI: 10.1016/j.mcp.2007.08.004.
2007 Du, R., An, X.R., Chen, Y.F., Qin, J. :
Some motifs were important for myostatin transcriptional regulation in sheep (Ovis aries). J Biochem Mol Biol 40:547-53, 2007. Pubmed reference: 17669271.
Du, R., An, X., Chen, Y., Qin, J. :
Functional analysis of the Myostatin gene promoter in sheep. Sci China C Life Sci 50:648-54, 2007. Pubmed reference: 17879064. DOI: 10.1007/s11427-007-0085-2.
Kijas, JW., Mcculloch, R., Hocking Edwards, JE., Oddy, VH., Lee, SH., van der Werf, J. :
Evidence for multiple alleles effecting muscling and fatness at the Ovine GDF8 locus. BMC Genet 8:80, 2007. Pubmed reference: 17996073. DOI: 10.1186/1471-2156-8-80.
Zhang, L., Yang, X., An, X., Chen, Y. :
Myostatin gene targeting in cultured China Han ovine myoblast cells. Animal 1:1401-8, 2007. Pubmed reference: 22444913. DOI: 10.1017/S1751731107000717.
2006 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., Georges, M. :
A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet 38:813-818, 2006. Pubmed reference: 16751773. DOI: 10.1038/ng1810.
Georges, M., Clop, A., Marcq, F., Takeda, H., Pirottin, D., Hiard, S., Tordoir, X., Caiment, F., Meish, F., Bibé, B., Bouix, J., Elsen, J.M., Eychenne, F., Laville, E., Larzul, C., Milenkovic, D., Tobin, J., Charlier, A.C. :
Polymorphic microRNA-target interactions: a novel source of phenotypic variation. Cold Spring Harb Symp Quant Biol 71:343-50, 2006. Pubmed reference: 17381315. DOI: 10.1101/sqb.2006.71.056.
2005 Du, R., Chen, YF., An, XR., Yang, XY., Ma, Y., Zhang, L., Yuan, XL., Chen, LM., Qin, J. :
Cloning and sequence analysis of myostatin promoter in sheep. DNA Seq 16:412-7, 2005. Pubmed reference: 16287620. DOI: 10.1080/10425170500226474.
Johnson, PL., McEwan, JC., Dodds, KG., Purchas, RW., Blair, HT. :
A directed search in the region of GDF8 for quantitative trait loci affecting carcass traits in Texel sheep. J Anim Sci 83:1988-2000, 2005. Pubmed reference: 16100053.
Johnson, PL., McEwan, JC., Dodds, KG., Purchas, RW., Blair, HT. :
Meat quality traits were unaffected by a quantitative trait locus affecting leg composition traits in Texel sheep. J Anim Sci 83:2729-35, 2005. Pubmed reference: 16282610.
2004 Laville, E., Bouix, J., Sayd, T., Bibe, B., Elsen, JM., Larzul, C., Eychenne, F., Marcq, F., Georges, M. :
Effects of a quantitative trait locus for muscle hypertrophy from Belgian Texel sheep on carcass conformation and muscularity. J Anim Sci 82:3128-37, 2004. Pubmed reference: 15542458.

Edit History


  • Created by Frank Nicholas on 04 Sep 2006
  • Changed by Frank Nicholas on 08 Oct 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 18 Nov 2013