Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations
Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations
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DOI：
10.1093/hmg/ddl130
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发表时间：
2006-07-01
影响因子：
3.5
通讯作者：
Zhang, Ya-Ping
中科院分区：
文献类型：
--
作者：
Kong, Qing-Peng;Bandelt, Hans-Jurgen;Zhang, Ya-Ping
了解人类线粒体DNA （mtDNA）的世界系统发育不仅对于评估特定mtDNA突变的致病作用，而且对于进行mtDNA单倍群与复杂疾病之间的可靠关联研究至关重要。在过去的几年里，mtDNA东亚部分系统发育的主要特征已经在完整测序的基础上确定，但仍然缺乏几个基础谱系的代表。此外，最近发表的一些完整的mtDNA序列显然不符合已知的系统发育树，并与已建立的命名法相冲突。为了完善东亚mtDNA树并解决数据冲突，我们首先对20个精心挑选的mtDNA（可能是新型亚单倍群的代表）进行了完全测序，然后，为了区分新型单倍群的诊断突变和私人变体，我们对大量样本收集应用了“基序搜索”程序。新的信息被纳入更新的东亚mtDNA树，包括超过1000个（接近）完整的mtDNA序列。对来自一系列疾病研究的mtDNA数据的重新评估证明了这种改进的mtDNA树在评估mtDNA突变的致病性方面的有用性。特别是，声称的突变G3316A、T3394C、A4833G和G15497A的致病作用似乎是最值得怀疑的，因为这些最初的说法来自轶事发现，而不是例如适当的关联研究。遵循基于这里提出的系统发育知识的指导方针可以帮助避免将来出现类似的问题。
Knowledge about the world phylogeny of human mitochondrial DNA (mtDNA) is essential not only for evaluating the pathogenic role of specific mtDNA mutations but also for performing reliable association studies between mtDNA haplogroups and complex disorders. In the past few years, the main features of the East Asian portion of the mtDNA phylogeny have been determined on the basis of complete sequencing efforts, but representatives of several basal lineages were still lacking. Moreover, some recently published complete mtDNA sequences did apparently not fit into the known phylogenetic tree and conflicted with the established nomenclature. To refine the East Asian mtDNA tree and resolve data conflicts, we first completely sequenced 20 carefully selected mtDNAs-likely representatives of novel sub-haplogroups-and then, in order to distinguish diagnostic mutations of novel haplogroups from private variants, we applied a 'motif-search' procedure to a large sample collection. The novel information was incorporated into an updated East Asian mtDNA tree encompassing more than 1000 (near-) complete mtDNA sequences. A reassessment of the mtDNA data from a series of disease studies testified to the usefulness of such a refined mtDNA tree in evaluating the pathogenicity of mtDNA mutations. In particular, the claimed pathogenic role of mutations G3316A, T3394C, A4833G and G15497A appears to be most questionable as those initial claims were derived from anecdotal findings rather than e.g. appropriate association studies. Following a guideline based on the phylogenetic knowledge as proposed here could help avoiding similar problems in the future.