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首页> 外文期刊>Genomics >Low mutational burden of individual acquired mitochondrial DNA mutations in brain.
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Low mutational burden of individual acquired mitochondrial DNA mutations in brain.

机译：个体获得性线粒体DNA突变在脑中的突变负担低。

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摘要

Neurons may be particularly susceptible to oxidative damage, which has been proposed to induce somatic mutations, particularly in mitochondrial DNA (mtDNA). Therefore, acquired mtDNA mutations might preferentially accumulate in the brain and could play a role in aging and neurodegenerative disorders. Recently, a somatic T to G mtDNA mutation at noncoding nucleotide position 414 was reported in fibroblasts specifically from elderly subjects, with mutational burdens of up to 50%. We screened for this mutation in brain-derived mtDNA from 8 Alzheimer's disease patients, 27 Parkinson's disease patients, 4 multiple system atrophy patients, and 44 controls using up to three RFLP analyses. A total of 73 of these subjects were over the age of 65. The 414 mutation was absent in all cases. Next, individual mtDNA fragments from 6 elderly subjects were cloned, and a total of 70 clones were sequenced. The 414 mutation was absent in all clones, though occasional sequence variations were identified at other sites in single clones. The 414 mutation also was absent in blood (n = 6) and fibroblasts (n = 11) from elderly subjects. Our data suggest that it is rare for any one particular acquired mtDNA mutation to reach levels in the brain that are functionally significant. This does not exclude the possibility that the cumulative burden of multiple, individually rare, acquired mutations impairs mitochondrial function. Copyright 2001 Academic Press.
机译：神经元可能特别容易受到氧化损伤的影响，氧化损伤已被提出诱导体细胞突变，尤其是在线粒体DNA（mtDNA）中。因此，获得性mtDNA突变可能优先在大脑中积累，并可能在衰老和神经退行性疾病中起作用。最近，据报道，特别是在老年受试者的成纤维细胞中，非编码核苷酸位置414发生体细胞T到G mtDNA突变，突变负担高达50％。我们使用多达3个RFLP分析，从8位阿尔茨海默氏病患者，27位帕金森氏病患者，4位多系统萎缩患者和44位对照中筛选了脑源性mtDNA中的这种突变。这些受试者中共有73名年龄在65岁以上。在所有情况下都没有414突变。接下来，克隆了来自6位老年受试者的单个mtDNA片段，并测序了70个克隆。在所有克隆中都没有414突变，尽管在单个克隆中的其他位点偶尔发现了序列变异。老年受试者的血液（n = 6）和成纤维细胞（n = 11）中也没有414突变。我们的数据表明，任何一种特定的获得性mtDNA突变都很少达到大脑中具有重要功能的水平。这并不排除多个（个别罕见）获得性突变的累积负担损害线粒体功能的可能性。版权所有2001，学术出版社。

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