Mitochondrial DNA Haplogroup D4a Is a Marker for Extreme Longevity in Japan

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dc.contributor.author Bilal, Erhan en_US
dc.contributor.author Rabadan, Raul en_US
dc.contributor.author Alexe, Gabriela en_US
dc.contributor.author Fuku, Noriyuki en_US
dc.contributor.author Ueno, Hitomi en_US
dc.contributor.author Nishigaki, Yutaka en_US
dc.contributor.author Fujita, Yasunori en_US
dc.contributor.author Ito, Masafumi en_US
dc.contributor.author Arai, Yasumichi en_US
dc.contributor.author Hirose, Nobuyoshi en_US
dc.contributor.author Ruckenstein, Andrei en_US
dc.contributor.author Bhanot, Gyan en_US
dc.contributor.author Tanaka, Masashi en_US
dc.date.accessioned 2012-01-12T16:41:19Z
dc.date.available 2012-01-12T16:41:19Z
dc.date.issued 2008-6-11 en_US
dc.identifier.citation Bilal, Erhan, Raul Rabadan, Gabriela Alexe, Noriyuki Fuku, Hitomi Ueno, Yutaka Nishigaki, Yasunori Fujita, Masafumi Ito, Yasumichi Arai, Nobuyoshi Hirose, Andrei Ruckenstein, Gyan Bhanot, Masashi Tanaka. "Mitochondrial DNA Haplogroup D4a Is a Marker for Extreme Longevity in Japan" PLoS ONE 3(6): e2421. (2008) en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/2144/3357
dc.description.abstract 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. en_US
dc.description.sponsorship Ministry of Education, Culture, Sports, Science, and Technology of Japan (A-15200051, C-18590317, B-18700541), Third Term Comprehensive 10-year Strategy for Cancer Control; Research Grants for Nervous and Mental Disorders of the Ministry of Health, Labour, and Welfare of Japan (17A-10); Kao Research Council for the Study of Healthcare Science; Takeda Science Foundation (I-2007, II-2007 to YN); Longevity Science of Ministry of Health, Labour, and Welfare of Japan; Cancer Institute of New Jersey; NJ Commission for Cancer Research; Center for Clinical and Translational Sciences at the Robert Wood Johnson Medical School, New Brunswick, NJ; the Simons Foundation; Ambrose Monell Foundation; Leon Levy Foundation; National Institutes of Health en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.title Mitochondrial DNA Haplogroup D4a Is a Marker for Extreme Longevity in Japan en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0002421 en_US
dc.identifier.pubmedid 18545700 en_US
dc.identifier.pmcid 2408726 en_US

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