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Defects in the function of this system result in some diaseases, many of which are multisystem disorders, prominently involving highly aerobic, postmitotic tissues. These defects can be caused by large\u2010scale rearrangements of mtDNA, by point mutations, or by nuclear gene mutations resulting in abnormalities in mtDNA. Although any of these mutations would be expected to produce a similar clinical phenotype by compromising oxidative phosphorylation, the surprising and puzzling result is that different clinical phenotypes are generally associated with specific mtDNA mutations. Moreover, the same mutation can produce a distinct clinical phenotype in different individuals or pedigrees. MtDNA rearrangements are also found in aged individuals, but at a subclinical level, suggesting that normal and pathological processes can differ by the effect of genetic or environmental factors on the error rate of mtDNA replication.<\/jats:p>","DOI":"10.1002\/bies.950181208","type":"journal-article","created":{"date-parts":[[2005,5,25]],"date-time":"2005-05-25T18:41:17Z","timestamp":1117046477000},"page":"983-991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Mitochondrial genetics and human disease"],"prefix":"10.1002","volume":"18","author":[{"given":"Lawrence I.","family":"Grossman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric A.","family":"Shoubridge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,5]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/290457a0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01799602"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)62067-7"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.11.5631"},{"key":"e_1_2_1_6_2","doi-asserted-by":"crossref","first-page":"6999","DOI":"10.1016\/S0021-9258(19)50527-0","article-title":"Nuclear respiratory factor\u20101 activation sites in genes encoding the \u03bc\u2010subunit of ATP synthase, eukaryotic initiation factor\u20102\u03b1, and tyrosine aminotransferase \u2013 specific interaction of purified NRF\u20101 with multiple target genes","volume":"267","author":"Chau C. 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