SEARCHING FOR GENES AFFECTING THE STRUCTURAL INTEGRITY OF THE MITOCHONDRIAL GENOME

Mendelian traits associated with qualitative or quantitative abnormali ties of mtDNA are presumably caused by mutations in nucleus-encoded ge nes that deleteriously interact with the mitochondrial genome. Qualita tive abnormalities of mtDNA are typically represented by pleioplasmic multiple mtDNA deletions, that are detected in stable tissues, includi ng skeletal muscle, of patients affected by Autosomal Dominant Chronic Progressive External Ophthalmoplegia. Quantitative abnormalities are represented by tissue-specific depletion of mtDNA, associated with dif ferent clinical presentations in infancy or childhood. Linkage analysi s and search for candidate genes are two complementary strategies aime d at identifying the genes responsible for these disorders.