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突尼斯百岁老人线粒体DNA全序列测序数据:检测单倍群关联及长寿的“中庸之道”

Data from complete mtDNA sequencing of Tunisian centenarians: testing haplogroup association and the "golden mean" to longevity.

作者信息

Costa Marta D, Cherni Lotfi, Fernandes Verónica, Freitas Fernando, Ammar El Gaaied Amel Ben, Pereira Luísa

机构信息

IPATIMUP (Instituto de Patologia e Imunologia Molecular da Universidade do Porto), Porto, Portugal.

出版信息

Mech Ageing Dev. 2009 Apr;130(4):222-6. doi: 10.1016/j.mad.2008.12.001. Epub 2008 Dec 24.

Abstract

Since the mitochondrial theory of ageing was proposed, mitochondrial DNA (mtDNA) diversity has been largely studied in old people, however complete genomes are still rare, being limited to Japanese and UK/US samples. In this work, we evaluated possible longevity associated polymorphisms/haplogroups in an African population, from Tunisia, by performing complete mtDNA sequencing. This population has a mixed Eurasian/sub-Saharan mtDNA gene pool, which could potentially facilitate the evaluation of association for sub-Saharan lineages. Sub-Saharan haplogroups were shown to be significantly less represented in centenarians (9.5%) than in controls (54.5%), but it is not possible to rule out an influence of population structure, which is high in these populations. No recurrent polymorphism were more frequent in centenarians than in controls, and although the Tunisian centenarians presented less synonymous and replacement polymorphisms than controls, this difference was not statistically significant. So far, it does not seem that centenarians have significantly less mildly deleterious substitutions, not only in Tunisia but also in Japanese and UK/US samples, as tested here, not favouring a "golden mean" to longevity.

摘要

自衰老的线粒体理论提出以来,线粒体DNA(mtDNA)多样性在老年人中得到了大量研究,然而完整基因组仍然很少见,仅限于日本以及英国/美国的样本。在这项研究中,我们通过对突尼斯一个非洲人群进行完整的mtDNA测序,评估了可能与长寿相关的多态性/单倍群。该人群拥有欧亚和撒哈拉以南混合的mtDNA基因库,这可能有助于评估撒哈拉以南谱系的关联性。结果显示,撒哈拉以南单倍群在百岁老人中的占比(9.5%)显著低于对照组(54.5%),但无法排除人口结构的影响,因为这些人群中的人口结构差异很大。百岁老人中没有出现比对照组更常见的反复出现的多态性,并且尽管突尼斯百岁老人的同义多态性和替代多态性比对照组少,但这种差异没有统计学意义。到目前为止,无论是在突尼斯,还是在此测试的日本以及英国/美国样本中,百岁老人似乎都没有显著更少的轻度有害替换,这并不支持存在一种长寿“黄金均值”的观点。

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