Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population
Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population
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DOI：
10.1007/s00439-007-0330-6
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发表时间：
2007-05-01
期刊：
影响因子：
5.3
通讯作者：
Tanaka, Masashi
中科院分区：
文献类型：
--
作者：
Alexe, Gabriela;Fuku, Noriyuki;Tanaka, Masashi
我们报告了对672个不相关的日本个体的完整线粒体（mtDNA）基因组进行重新分析的新结果，这些个体按表型分为7个相等大小的组：糖尿病患者，糖尿病伴严重血管病患者，健康的非肥胖年轻男性，肥胖年轻男性，阿尔茨海默病患者，帕金森病患者和百岁老人。每个表型有27个已知单倍群的96个样本：A、B4 a、B4 B、B4 c、B*、B5、D*、F1、F2、M*、M7 a、M7 B b、M8、M9、D4 a、D4 b1、D4 b2、D4 d、D4 e、D4 g、D4 h、D5、G、Z、M*、N9 a和N9 B b。一个t检验比较样本的分数在一个单倍型组健康的年轻男性表现出显着丰富的单倍型组D4 a，D5和D4 b2百岁老人。D4 b2富集限于61个样品中具有同义突变9296 C> T的40个样品的亚组。我们将这个簇鉴定为一个独特的单倍群，并将其标记为D4 b2b。使用详尽的程序，我们构建了百岁老人的“突变模式”的完整列表，并显示最重要的模式是D4 a，D5和D4 b2b。我们认为，如果选择寿命只出现一次，这可能是一个常染色体事件，可以追溯到D兆组出现后，但在D4 a，D5，D4 b2b的合并时间。使用一个简单的程序，我们估计这一事件发生在24.4 +/- 0.9 kYBP。
We report new results from the re-analysis of 672 complete mitochondrial (mtDNA) genomes of unrelated Japanese individuals stratified into seven equal sized groups by the phenotypes: diabetic patients, diabetic patients with severe angiopathy, healthy non-obese young males, obese young males, patients with Alzheimer's disease, patients with Parkinson's disease and centenarians. Each phenotype had 96 samples over 27 known haplogroups: A, B4a, B4b, B4c, B*, B5, D*, F1, F2, M*, M7a, M7b, M8, M9, D4a, D4b1, D4b2, D4d, D4e, D4g, D4h, D5, G, Z, M*, N9a, and N9b. A t-test comparing the fraction of samples in a haplogroup to healthy young males showed a significant enrichment of haplogroups D4a, D5, and D4b2 in centenarians. The D4b2 enrichment was limited to a subgroup of 40 of 61 samples which had the synonymous mutation 9296C > T. We identified this cluster as a distinct haplogroup and labeled it as D4b2b. Using an exhaustive procedure, we constructed the complete list of "mutation patterns" for centenarians and showed that the most significant patterns were in D4a, D5, and D4b2b. We argue that if a selection for longevity appeared only once, it was probably an autosomal event which could be dated to after the appearance of the D mega-group but before the coalescent time of D4a, D5, and D4b2b. Using a simple procedure, we estimated that this event occurred 24.4 +/- 0.9 kYBP.