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Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-IIb-perinatal-extraocular

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Abstract

Myosin heavy chain (MyHC) is the major contractile protein of muscle. We report the first complete cosmid cloning and definitive physical map of the tandemly linked human skeletal MyHC genes at 17p13.1. The map provides new information on the order, size, and relative spacing of the genes, and it resolves uncertainties about the two fastest twitch isoforms. The physical order of the genes is demonstrated to contrast with the temporal order of their developmental expression. Furthermore, nucleotide sequence comparisons allow an approximation of the relative timing of five ancestral duplications that created distinct genes for the six isoforms. A firm foundation is provided for molecular analysis in patients with suspected primary skeletal myosinopathies and for detailed modelling of the hypervariable surface loops which dictate myosin's kinetic properties.

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Authors and Affiliations

  1. Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Joseph B. Shrager, Philippe R. Desjardins, James M. Burkman, Stephane K. Konig, Leonard Su, Megha C. Shah, Evelyn Bricklin & Hansell H. Stedman

  2. Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Douglas R. Stewart, Rebecca Hoffman & Michael R. Rickels

  3. Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Manu Tewari & Neal A. Rubinstein

  4. Laboratoire d'Histologie-Embryologie, Faculte de Medecine Cochin Port Royale, Universite Rene Descartes, Paris, France

    Eric H. Jullian

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  1. Joseph B. Shrager
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  2. Philippe R. Desjardins
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  4. Stephane K. Konig
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  10. Rebecca Hoffman
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  14. Hansell H. Stedman
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Shrager, J.B., Desjardins, P.R., Burkman, J.M. et al. Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-IIb-perinatal-extraocular. J Muscle Res Cell Motil 21, 345–355 (2000). https://doi.org/10.1023/A:1005635030494

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