The human beta-myosin heavy chain gene: sequence diversity and functional characteristics of the protein.
The beta-myosin heavy chain gene (MYH7) encodes the motor protein that drives myocardial contraction. It has been proven to be a disease gene for hypertrophic cardiomyopathy (HCM). We analyzed the DNA sequence variation of MYH7 (about 16 kb) of eight individuals: six patients with HCM and two healthy controls. The overall DNA sequence identity was up to 97.2% compared to Jaenicke and coworkers (Jaenicke et al. [1990] Genomics 8:194-206), while the corresponding amino acid sequences revealed 100% identity. In HCM patients, eleven nucleotide substitutions were identified but no causative disease mutation was found: six were detected in coding, four in intronic, and one in 5' regulatory regions. The average nucleotide diversity across this locus was 0.015% with an average of 0.02% in the coding and 0.012% in the noncoding sequence. Analysis of the kinetic behaviour of beta-MHC in the intact contractile structure of normal individuals and HCM patients revealed apparent rate constants of tension development ranging between 1.58 s(-1) and 1.48 s(-1).
Wendel
B
B
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Reinhard
R
R
Wachtendorf
U
U
Zacharzowsky
U B
UB
Osterziel
K J
KJ
Schulte
H D
HD
Haase
H
H
Hoehe
M R
MR
Morano
I
I
D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000503:physiopathology*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009200:Myocardial Contraction / Q000502:physiology; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*
D004247:DNA; D018995:Myosin Heavy Chains