Molecular cloning and chromosomal localization of a gene coding for human cardiac myosin heavy-chain

alpha- and beta-human cardiac myosin heavy-chain (MHC) genes, which correspond to MYH6 and MYH7, respectively, according to Human Gene Mapping nomenclature, were isolated from human genomic and cDNA clones, using two rat cardiac pCMHC26: alpha-MHC type; and pCMHC5: beta-MHC type as probes, and characterized. The alpha-MHC type cardiac genomic DNA clone and the beta-MHC type cardiac cDNA clone were used as probes in the Southern analysis of human genomic DNA from human-Chinese hamster or human-mouse somatic cell hybrids. The results showed that the human cardiac MHC gene is assigned to chromosome 14 and the human cardiac and skeletal MHC genes do not cosegregate as do the mouse cardiac and skeletal MHC genes. For further analysis, a regional mapping method was used. DNA from 4 human deletion and 3 human duplication cell line were prepared for southern blotting, hybridized with human cardiac alpha- and beta-MHC DNA probes, and the hybridization intensity relative to 46, XX or 46, XY DNA was estimated. The results showed that two human cardiac MHC genes segregated with the 14cenq13 region of the long arm of human chromosome 14. In situ hybridization of 3H-labeled human cardiac alpha-MHC probe to normal human metaphase chromosome independently confirmed this result.