title: Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations.
abstract: 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.
authors.affiliation: Laboratory of Cellular and Molecular Evolution, and Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. kongqp@yahoo.com.cn
authors.forename: Qing-Peng
authors.initials: QP
authors.lastname: Kong
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Bandelt
authors.forename: Chang
authors.initials: C
authors.lastname: Sun
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
authors.forename: Alessandro
authors.initials: A
authors.lastname: Achilli
authors.forename: Cheng-Ye
authors.initials: CY
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Zhu
authors.forename: Shi-Fang
authors.initials: SF
authors.lastname: Wu
authors.forename: Antonio
authors.initials: A
authors.lastname: Torroni
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D005202:Asia, Eastern; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010802:Phylogeny; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial