Evolution meets disease: penetrance and functional epistasis of mitochondrial tRNA mutations.

ABSTRACT: About half of the mitochondrial DNA (mtDNA) mutations causing diseases in humans occur in tRNA genes. Particularly intriguing are those pathogenic tRNA mutations than can reach homoplasmy and yet show very different penetrance among patients. These mutations are scarce and, in addition to their obvious interest for understanding human pathology, they can be excellent experimental examples to model evolution and fixation of mitochondrial tRNA mutations. To date, the only source of this type of mutations is human patients. We report here the generation and characterization of the first mitochondrial tRNA pathological mutation in mouse cells, an m.3739G>A transition in the mitochondrial mt-Ti gene. This mutation recapitulates the molecular hallmarks of a disease-causing mutation described in

SUBMITTER: Moreno-Loshuertos R 

PROVIDER: S-EPMC3080857 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature