Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan.
Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan.
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DOI：
10.1371/journal.pone.0002421
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发表时间：
2008-06-11
期刊：
影响因子：
3.7
通讯作者：
Tanaka M
中科院分区：
文献类型：
--
作者：
Bilal E;Rabadan R;Alexe G;Fuku N;Ueno H;Nishigaki Y;Fujita Y;Ito M;Arai Y;Hirose N;Ruckenstein A;Bhanot G;Tanaka M
我们报告了对112名日本半百岁老人(105岁以上)的完整线粒体DNA(MtDNA)序列的分析结果，结合以前发表的96名患者的数据，这些患者分别属于三种非疾病表型：百岁老人(99-105岁)、健康的非肥胖男性、肥胖的年轻男性和四种疾病表型、有血管病变和无血管病变的糖尿病患者以及阿尔茨海默病和帕金森病患者。我们用两种不同的方法分析了线粒体多态与长寿表型的相关性。我们首先使用穷举算法来识别至少五个个体共有的所有最大多态模式，并定义每个表型中相对于健康正常人群的模式丰富的显著分数。我们的研究证实了在之前的一项研究中观察到的相关性，即D分支中单倍群的层次结构丰富，以延长寿命。对于极端长寿的表型，我们看到一个具有统计学意义的信号：在D4a单倍组中，百岁老人和半超百岁老人中某些“有益”模式的逐渐丰富。然后，我们使用SNP-SNP协方差矩阵的主成分谱分析将测量的特征值与高斯数据集上的特征值的零分布进行比较，以确定数据中的相关性(由于寿命)是由于突变本身的某些属性还是由于种群结构造成的。结论是，这种相关性完全是由于种群结构(系统发育树)。我们没有发现有功能的mtDNA SNP与寿命相关的信号。这种相关性来自种群结构，这一事实表明搭便车是常染色体事件的一种可能解释。
We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99–105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain “beneficial” patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.
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影响因子：
168.9
作者：
Tanaka, M;Gong, JS;Yagi, K
通讯作者：
Yagi, K
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
64.8
作者：
Gibbs, RA;Belmont, JW;Tanaka, T
通讯作者：
Tanaka, T
影响因子：
3.5
作者：
Kong, Qing-Peng;Bandelt, Hans-Jurgen;Zhang, Ya-Ping
通讯作者：
Zhang, Ya-Ping
影响因子：
5.3
作者：
Alexe, Gabriela;Fuku, Noriyuki;Tanaka, Masashi
通讯作者：
Tanaka, Masashi