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 dri ves myocardial contraction. It has been proven to be a disease gene for hyp ertrophic cardiomyopathy (HCM). We analyzed the DNA sequence variation of M YH7 (about 16 kb) of eight individuals: six patients with HCM and two healt hy 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 t he corresponding amino acid sequences revealed 100% identity. In HCM patien ts, eleven nucleotide substitutions were identified but no causative diseas e mutation was found. six were detected in coding, four in intronic, and on e in 5' regulatory regions. The average nucleotide diversity across this lo cus was 0.015% with an average of 0.02% in the coding and 0.012% in the non coding sequence. Analysis of the kinetic behaviour of beta -MHC in the inta ct contractile structure of normal individuals and HCM patients revealed ap parent rate constants of tension development ranging between 1.58 s(-1) and 1.48 s(-1). (C) 2000 Wiley-Liss, Inc.