title: Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-ILb-perinatal-extraocular.
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.
authors.affiliation: Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Shrager
authors.forename: P R
authors.initials: PR
authors.lastname: Desjardins
authors.forename: J M
authors.initials: JM
authors.lastname: Burkman
authors.forename: S K
authors.initials: SK
authors.lastname: Konig
authors.forename: S K
authors.initials: SK
authors.lastname: Stewart
authors.forename: L
authors.initials: L
authors.lastname: Su
authors.forename: M C
authors.initials: MC
authors.lastname: Shah
authors.forename: E
authors.initials: E
authors.lastname: Bricklin
authors.forename: M
authors.initials: M
authors.lastname: Tewari
authors.forename: R
authors.initials: R
authors.lastname: Hoffman
authors.forename: M R
authors.initials: MR
authors.lastname: Rickels
authors.forename: E H
authors.initials: EH
authors.lastname: Jullian
authors.forename: N A
authors.initials: NA
authors.lastname: Rubinstein
authors.forename: H H
authors.initials: HH
authors.lastname: Stedman
mesh_terms: D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003360:Cosmids; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology* / Q000254:growth & development; D009135:Muscular Diseases / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics*; D009801:Oculomotor Muscles / Q000196:embryology / Q000254:growth & development; D020033:Protein Isoforms / Q000235:genetics; D012518:Sarcomeres / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D020033:Protein Isoforms; D018995:Myosin Heavy Chains