Maternal Inheritance and Study of Human Mitochondrial Genome

Several diseases with non-mendelian maternal inheritance patterns have been described, some of which appeared to be associated with abnormal mitochondrial structure or function and might result from the inheritance of an abnormal mitochondrial genome. New techniques in molecular genetics should clarify the molecular basis of these maternally inherited developmental disorders. From families with maternally inherited mitochondrial disorders we conducted a search for an alteration in nucleotide analysis of the mitochondrial DNA obtained from the lymphocytes of the patients. Although it was possible to identify a single substitution (CTT/ATT) in one of five clones in which were transcribed the gene of cytochrome C oxidase subunit II, it was impossible to define the mismatched site by the method of RNA/DNA mapping (Myers, 1985) using a labelled RNA probe containing a cytochrome C oxidase gene which was obtained from normal placenta cells. A congenital myotonic dystrophy is known to be inherited through an autosomal dominant gene, and yet the age of onset and the severity of the disease are influenced by non-mendelian maternal inheritance. We previously proposed that an abnormality of bile acid metabolism could affect the fetus, resulting perhaps in delayed development. A possible model for this effect might involve the interaction of mitochondrial function with an autosomal gene product, leading to erroneous replication with a mutant form of the polymerase subunit.