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首页> 外文会议>Asian Society for Mitochondrial Research and Medicine >Evolutional Analysis in Determining Pathogenic versus Nonpathogenic Mutations of ATPase 6 in Human Mitochondriopathy
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Evolutional Analysis in Determining Pathogenic versus Nonpathogenic Mutations of ATPase 6 in Human Mitochondriopathy

机译：在人体线粒体病变中确定ATP酶6的致病与非致病性突变的进化分析

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Because mitochondrial ATPase 6 plays an important role in ATP synthesis, mutations affecting ATPase 6 can undoubtedly cause human diseases. In contrast, the ATPase 6 gene is known to be a fast-evolving gene and has generated enough polymorphisms to allow identity investigation for forensic casework. To investigate these seemingly opposite views, we analyzed amino acid sequences of ATPase 6 in at least 1,266 humans, 102 mammals, and 213 vertebrates. The result showed that the amino acids of human ATPase 6 could be divided into the following four groups. Amino acid residue 192 (affected by alteration at nt 9101) and 79 other residues were variable, and therefore substitutions of these residues would not be pathogenic. Amino acid residue 156 (affected by alteration at nt 8993) and 93 other residues were conserved in Homo sapiens, but not in Mammalia. Therefore, they were potentially pathogenic if altered. Function studies would be necessary to confirm their role in pathogenesis. Amino acid residue 217 (affected by alteration at nt 9176) and 9 other residues were conserved across all species, including S. cerevisiae and E. coli. Mutations involving these residues would be pathogenic, some of which might even be life threatening. The remainder (42 residues) were conserved in Mammalia, but not in yeast and E. coli. They were probably pathogenic if mutated. The classification proposed in this study may, therefore, provide an algorithm for a diagnostic approach when a newly identified change of ATPase 6 is suspected for human mitochondriopathy.
机译：由于线粒体ATPase 6在ATP合成中起重要作用，因此影响ATPase 6的突变无疑会导致人类疾病。相反，已知ATP酶6基因是一种快速发展的基因，并且产生足够的多态性，以允许对法医案例的身份调查。为了调查这些看似相反的观点，我们分析了ATP酶6的氨基酸序列在至少1,266人，102个哺乳动物和213个脊椎动物中。结果表明，人ATP酶6的氨基酸可分为以下四组。氨基酸残基192（受到NT 9101的改变）和79个其他残基的影响是可变的，因此这些残留物的取代不会是致病性的。氨基酸残基156（受NT 8993的改变影响）和93个其他残留物在同源Sapiens中保守，但不包括在哺乳动物中。因此，如果改变，它们是潜在的致病性。函数研究是必要的，以证实他们在发病机制中的作用。氨基酸残基217（受到NT 9176的改变的影响）和9种其他残留物在所有物种上保守，包括酿酒酵母和大肠杆菌。涉及这些残留物的突变将是致病性的，其中一些可能甚至可能危及生命。其余（42个残基）在哺乳动物中保存，但不在酵母和大肠杆菌中保存。如果突变，它们可能是致病性。因此，在本研究中提出的分类可以提供一种诊断方法的算法，当怀疑对人的线粒体提高病症的新发现的ATP酶6变化时。

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