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A deletion in the bovine myostatin gene causes the double–muscled phenotype in cattle


An exceptional muscle development commonly referred to as ‘double-muscled’ (Fig. 1) has been seen in several cattle breeds and has attracted considerable attention from beef producers. Double-muscled animals are characterized by an increase in muscle mass of about 20%, due to general skeletal-muscle hyperplasia—that is, an increase in the number of muscle fibers rather than in their individual diameter1. Although the hereditary nature of the double-muscled condition was recognized early on, the precise mode of inheritance has remained controversial; monogenic (dominant and recessive), oligogenic and polygenic models have been proposed2. In the Belgian Blue cattle breed (BBCB)4, segregation analysis performed both in experimental crosses3 and in the outbred population suggested an autosomal recessive inheritance. This was confirmed when the muscular hypertrophy (mh) locus was mapped 3.1 cM from microsatellite TGLA44 on the centromeric end of bovine chromosome 2 (ref. 5). We used a positional candidate approach to demonstrate that a mutation in bovine MSTN, which encodes myostatin, a member of the TGFβ superfamily, is responsible for the double-muscled phenotype. We report an 11-bp deletion in the coding sequence for the bioactive carboxy-termihal domain of the protein causing the muscular hypertrophy observed in Belgian Blue cattle.

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  1. Hanset, R. The major gene of muscular hypertrophy. in The Belgian Blue cattle breed. in Breeding for Disease Resistance in Farm Animals (eds Owen, J. B. & Axford, R.F.E.) 467–478 (C.A.B. International, Oxford, 1991).

    Google Scholar 

  2. Ménissier, F. Present state of knowledge about the genetic determination of muscular hypertrophy or the double muscled trait in cattle. in Current Topics in Veterinary Medicine and Animal Science, vol 16: Muscle Hyertrophy of Genetic Origin and Its Use to Improve Beef Production (eds King, J.W.B. & Ménissier, F.) 387–428 (Martinus Nijhoff, Norwell, Massachusetts, 1982).

    Google Scholar 

  3. Hanset, R. & Michaux, C. On the genetic determinism of muscular hypertrophy in the Belgian White and Blue cattle breed. I. Experimental data. Genet. Sel. Evol. 17, 359–368 (1985).

    Article  CAS  Google Scholar 

  4. Hanset, R. & Michaux, C. On the genetic determinism of muscular hypertrophy in the Belgian White and Blue cattle breed: II. Population data. Genet Sel. Evol. 17, 369–386 (1985).

    Article  CAS  Google Scholar 

  5. Charlier, C. et al. The mh gene causing double-muscling in cattle maps to bovine chromosome 2. Mamm. Genome 6, 788–792 (1995).

    Article  CAS  PubMed  Google Scholar 

  6. Solinas-Toldo, S., Lengauer, C. & Fries, R. Comparative genome map of man and cattle. Genomics 27, 489–496 (1995).

    Article  CAS  PubMed  Google Scholar 

  7. Fisher, S.R., Beever, J.E. & Lewin, H.A. Genetic mapping of COL3AI to bovine chromosome 2. Mamm. Genome 8, 76–77 (1996).

    Article  Google Scholar 

  8. O'Brien, S.J. et al. Anchored reference loci for comparative genome mapping in mammals. Nature Genet. 3, 103–112 (1993).

    Article  CAS  PubMed  Google Scholar 

  9. Lyons, A.L. et al. Comparative anchor tagged sequences (CATS) for integrative mapping of mammalian genomes. Nature Genet. 15, 47–56 (1996).

    Article  Google Scholar 

  10. Kappes, S.M. et al. A second-generation linkage map of the bovine genome. Genome Res. 7, 235–249 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. McPherron, A.C., Lawler, A.M. & Lee, S.-J. Regulation of skeletal muscle mass in mice by a new TGFβ superfamily member. Nature 387, 83–90 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Walter, M.A., Spillett, D.J., Thomas, P., Weissenbach, J. & Goodfellow, P.N. A method for constructing radiation hybrid maps of whole genomes. Nature Genet. 7, 22–28 (1994).

    Article  CAS  PubMed  Google Scholar 

  13. Hudson, T.G. et al. An STS-based map of the human genome. Science 270, 1945–1954 (1995), with supplementary data from the Whitehead Institute/MIT Center for Genome Research, Human Genetic Mapping Project, data release 11.9 (May 1997).

    Article  CAS  PubMed  Google Scholar 

  14. McPherron, A.C. & Lee, S.-J. The transforming growth factor β superfamily. in Growth Factors and Cytokines in Health and Disease, vol 1B (eds LeRoith, D. & Bondy, C.) 357–393 (Jai Publishing, Greenwich, Connecticut, 1996).

    Google Scholar 

  15. Dunner, S. et al. Towards interbreed IBD fine mapping of the mh locus: double-muscling in the Asturiana de los Valles breed involves the same locus as in the Belgian Blue cattle breed. Mamm. Genome 8, 430–435 (1997).

    Article  CAS  PubMed  Google Scholar 

  16. Georges, M. et al. Mapping quantitative trait loci controlling milk production by exploiting progeny testing. Genetics 139, 907–920 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Lathrop, M. & Lalouel, J.M. Easy calculations of lodscores and genetic risk on small computers. Am. J. Hum. Genet. 36, 460–465 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Cottingham, R.W. Jr., Idury, R.M. & Schäffer, A.A. Faster sequential genetic linkage computations. Am. J. Hum. Genet. 53, 252–263 (1993).

    PubMed  PubMed Central  Google Scholar 

  19. Libert, F., Lefort, A., Okimoto, R., Womack, J. & Georges, M. Construction of a bovine genomic library of large yeast artificial chromosome clones. Genomics 18, 270–276 (1993).

    Article  CAS  PubMed  Google Scholar 

  20. Hunter, K.W. et al. Toward the construction of integrated physical and genetic maps of the mouse genome using interspersed repetitive sequence PCR (IRS–PCR) genomics. Genome Res. 6, 290–299 (1996).

    Article  CAS  PubMed  Google Scholar 

  21. Lenstra, J.A., van Boxtel, J.A.F., Zwaagstra, K.A. & Schwerin, M. Short interspersed nuclear element (SINE) sequences of the Bovidae. Anim. Genet. 24, 33–39 (1993).

    Article  CAS  PubMed  Google Scholar 

  22. Cornélis, F. et al. Identification of a CA repeat at the TCRA locus using yeast artificial chromosomes: a general method for generating highly polymorphic markers at chosen loci. Genomics 13, 820–825 (1992).

    Article  PubMed  Google Scholar 

  23. Chirgwin, J.M., Przybyla, A.E., MacDonald, R.J. & Rutter, W.J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18, 5294–5299 (1979).

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Michel Georges.

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Grobet, L., Royo Martin, L., Poncelet, D. et al. A deletion in the bovine myostatin gene causes the double–muscled phenotype in cattle. Nat Genet 17, 71–74 (1997).

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