[Molecular cloning and characterization of a gene coding for human cardiac myosin heavy-chain]

In vertebrates, the myosin heavy chain (MHC) genes are very closely related at the nucleotide sequence level. Amino acid sequence comparison of the human cardiac alpha- and beta-MHC have demonstrated that there are, at least, 7 isoform-specific divergent regions, including important binding protein-related sites such as ATP, actin and myosin light chain. It has been reported that in the rat, there are 8 isoform-specific divergent regions. The 7th divergent area which is thought to mediate thick filament in the light meromyosin region in the rat is not apparent in the human. Also, recently, 9 kinds of human genomic MHC genes have been investigated. The 4 human skeletal MHC genes are clustered at chromosome region 17 pter-p11, 17p13. The cardiac alpha- and beta-MHC genes are in tandem and mapped to chromosome region 14q11.2, the smooth muscle MHC gene is mapped to 16q11.2 and two nonmuscle MHC genes are mapped to chromosomes 17 and 22. We are studying the relationship between hypertrophic cardiomyopathy and the cardiac MHC gene, and between other MHC genes and other cardiac diseases.