Mitochondrial DNA Haplogroup D4a Is a Marker for Extreme Longevity in Japan
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{"title"=>"Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan", "type"=>"journal", "authors"=>[{"first_name"=>"Erhan", "last_name"=>"Bilal", "scopus_author_id"=>"16201727100"}, {"first_name"=>"Raul", "last_name"=>"Rabadan", "scopus_author_id"=>"15071174300"}, {"first_name"=>"Gabriela", "last_name"=>"Alexe", "scopus_author_id"=>"6602169796"}, {"first_name"=>"Noriyuki", "last_name"=>"Fuku", "scopus_author_id"=>"6508346353"}, {"first_name"=>"Hitomi", "last_name"=>"Ueno", "scopus_author_id"=>"16204621300"}, {"first_name"=>"Yutaka", "last_name"=>"Nishigaki", "scopus_author_id"=>"7005508556"}, {"first_name"=>"Yasunori", "last_name"=>"Fujita", "scopus_author_id"=>"36051787100"}, {"first_name"=>"Masafumi", "last_name"=>"Ito", "scopus_author_id"=>"56416851400"}, {"first_name"=>"Yasumichi", "last_name"=>"Arai", "scopus_author_id"=>"55754938000"}, {"first_name"=>"Nobuyoshi", "last_name"=>"Hirose", "scopus_author_id"=>"7103121952"}, {"first_name"=>"Andrei", "last_name"=>"Ruckenstein", "scopus_author_id"=>"6603888936"}, {"first_name"=>"Gyan", "last_name"=>"Bhanot", "scopus_author_id"=>"7004654825"}, {"first_name"=>"Masashi", "last_name"=>"Tanaka", "scopus_author_id"=>"7408427282"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"352109507", "sgr"=>"48749085727", "doi"=>"10.1371/journal.pone.0002421", "scopus"=>"2-s2.0-48749085727", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"18545700"}, "id"=>"2ba86457-3bbb-3568-90dc-1988270c93d5", "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.", "link"=>"http://www.mendeley.com/research/mitochondrial-dna-haplogroup-d4a-marker-extreme-longevity-japan", "reader_count"=>52, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>5, "Researcher"=>13, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>4, "Student > Master"=>3, "Other"=>4, "Student > Bachelor"=>2, "Professor"=>6}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>5, "Researcher"=>13, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>4, "Student > Master"=>3, "Other"=>4, "Student > Bachelor"=>2, "Professor"=>6}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>8, "Mathematics"=>1, "Agricultural and Biological Sciences"=>26, "Medicine and Dentistry"=>11, "Design"=>1, "Neuroscience"=>1, "Psychology"=>1, "Social Sciences"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>26}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Mathematics"=>{"Mathematics"=>1}}, "reader_count_by_country"=>{"New Zealand"=>1, "United States"=>3}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/459030", "https://ndownloader.figshare.com/files/459048", "https://ndownloader.figshare.com/files/459074"], "description"=>"<div><p>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.</p></div>", "links"=>[], "tags"=>["mitochondrial", "dna", "haplogroup", "d4a", "longevity", "japan"], "article_id"=>150437, "categories"=>["Genetics"], "users"=>["Erhan Bilal", "Raul Rabadan", "Gabriela Alexe", "Noriyuki Fuku", "Hitomi Ueno", "Yutaka Nishigaki", "Yasunori Fujita", "Masafumi Ito", "Yasumichi Arai", "Nobuyoshi Hirose", "Andrei Ruckenstein", "Gyan Bhanot", "Masashi Tanaka"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002421.s001", "https://dx.doi.org/10.1371/journal.pone.0002421.s002", "https://dx.doi.org/10.1371/journal.pone.0002421.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Mitochondrial_DNA_Haplogroup_D4a_Is_a_Marker_for_Extreme_Longevity_in_Japan/150437", "title"=>"Mitochondrial DNA Haplogroup D4a Is a Marker for Extreme Longevity in Japan", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-06-11 00:07:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/929364"], "description"=>"<p>Age distribution across the samples (JD, ND, HN, KA, PD, TC/GC, SSC).</p>", "links"=>[], "tags"=>["samples"], "article_id"=>599792, "categories"=>["Genetics"], "users"=>["Erhan Bilal", "Raul Rabadan", "Gabriela Alexe", "Noriyuki Fuku", "Hitomi Ueno", "Yutaka Nishigaki", "Yasunori Fujita", "Masafumi Ito", "Yasumichi Arai", "Nobuyoshi Hirose", "Andrei Ruckenstein", "Gyan Bhanot", "Masashi Tanaka"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002421.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Age_distribution_across_the_samples_JD_ND_HN_KA_PD_TC_GC_SSC_/599792", "title"=>"Age distribution across the samples (JD, ND, HN, KA, PD, TC/GC, SSC).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-11 02:43:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/929454"], "description"=>"<p>The red region represents 124 patterns with q-value<0.05. The pattern enrichment score used here is L<sub>P</sub>.</p>", "links"=>[], "tags"=>["scores", "1386", "maximal", "patterns", "mutations"], "article_id"=>599886, "categories"=>["Genetics"], "users"=>["Erhan Bilal", "Raul Rabadan", "Gabriela Alexe", "Noriyuki Fuku", "Hitomi Ueno", "Yutaka Nishigaki", "Yasunori Fujita", "Masafumi Ito", "Yasumichi Arai", "Nobuyoshi Hirose", "Andrei Ruckenstein", "Gyan Bhanot", "Masashi Tanaka"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002421.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_significance_scores_for_the_1386_maximal_patterns_of_mutations_in_the_data_/599886", "title"=>"The significance scores for the 1386 maximal patterns of mutations in the data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-11 02:44:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/929554"], "description"=>"<p>3206T, 14979C and 8473C are markers for D4a. SNP 10410C is enriched 80% in D4a vs its wild-type form 10410T.</p>", "links"=>[], "tags"=>["enrichment", "snps", "sets", "96", "centenarians", "semi", "112", "semi-supercentenarians", "compared"], "article_id"=>599980, "categories"=>["Genetics"], "users"=>["Erhan Bilal", "Raul Rabadan", "Gabriela Alexe", "Noriyuki Fuku", "Hitomi Ueno", "Yutaka Nishigaki", "Yasunori Fujita", "Masafumi Ito", "Yasumichi Arai", "Nobuyoshi Hirose", "Andrei Ruckenstein", "Gyan Bhanot", "Masashi Tanaka"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002421.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Significance_score_L_S_at_q_value_/599980", "title"=>"Significance score <i>L<sub>S</sub></i> at q-value<0.05 for the enrichment of SNPs in the three data sets – 96 centenarians, 96+112 centenarians and semi supercentenarians, 112 semi-supercentenarians compared to healthy normals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-11 02:46:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/929653"], "description"=>"<p>In this analysis, we used the 124 positive patterns from <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002421#pone-0002421-g002\" target=\"_blank\">Figure 2</a> with q-value<0.05.</p>", "links"=>[], "tags"=>["beneficial", "patterns", "haplogroups"], "article_id"=>600086, "categories"=>["Genetics"], "users"=>["Erhan Bilal", "Raul Rabadan", "Gabriela Alexe", "Noriyuki Fuku", "Hitomi Ueno", "Yutaka Nishigaki", "Yasunori Fujita", "Masafumi Ito", "Yasumichi Arai", "Nobuyoshi Hirose", "Andrei Ruckenstein", "Gyan Bhanot", "Masashi Tanaka"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002421.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proportion_of_beneficial_patterns_in_haplogroups_8202_8202_100_215_Number_of_positive_patterns_found_in_haplogroup_Total_number_of_patterns_found_in_haplogroup_/600086", "title"=>"Proportion of beneficial patterns in haplogroups  = 100× (Number of positive patterns found in haplogroup)/(Total number of patterns found in haplogroup).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-11 00:01:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/929748"], "description"=>"<p>Note the presence of a group of 6 SNPs (upper left hand red box) strongly associated with longevity. These are: 3206T, 10410C, 8473C, 14979C, 152C and 16129A. The ones in bold are the same as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002421#pone-0002421-g003\" target=\"_blank\">Figure 3</a> and are markers for D4a. The locations 152 and 16129 are known mutational hotspots in the hypervariable regions HVS-II and HVS-I respectively and hence their correlation with longevity cannot be considered significant.</p>", "links"=>[], "tags"=>["matrix", "snps"], "article_id"=>600184, "categories"=>["Genetics"], "users"=>["Erhan Bilal", "Raul Rabadan", "Gabriela Alexe", "Noriyuki Fuku", "Hitomi Ueno", "Yutaka Nishigaki", "Yasunori Fujita", "Masafumi Ito", "Yasumichi Arai", "Nobuyoshi Hirose", "Andrei Ruckenstein", "Gyan Bhanot", "Masashi Tanaka"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002421.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heat_map_of_the_agreement_matrix_for_SNPs_across_significant_patterns_/600184", "title"=>"Heat map of the agreement matrix for SNPs across significant patterns.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-11 00:03:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/929869"], "description"=>"<p>We compare the D clade samples with the rest of the Japanese samples. Enrichment of the SNP was determined using a chi-squared test at 0.0001 significance level. The choice of mtSNPs in Hapmap was too sparse to resolve the D samples into subhaplogroups. We also cannot correlate SNP 14979C with autosomal SNPs because no D4a defining markers were available in the HapMap dataset.</p>", "links"=>[], "tags"=>["enhanced", "snps", "clade", "japanese", "samples", "hapmap"], "article_id"=>600299, "categories"=>["Genetics"], "users"=>["Erhan Bilal", "Raul Rabadan", "Gabriela Alexe", "Noriyuki Fuku", "Hitomi Ueno", "Yutaka Nishigaki", "Yasunori Fujita", "Masafumi Ito", "Yasumichi Arai", "Nobuyoshi Hirose", "Andrei Ruckenstein", "Gyan Bhanot", "Masashi Tanaka"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002421.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_top_enhanced_SNPs_in_the_D_clade_in_the_Japanese_samples_in_Hapmap_5_/600299", "title"=>"The top enhanced SNPs in the D clade in the Japanese samples in Hapmap [5].", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-06-11 00:04:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/929906"], "description"=>"<p>Column 2 shows the haplogroup specificity for the SNP. The next two columns show the nucleotide in rCRS and the mutation. The last two columns are for the corresponding gene and the ‘sense’ of the mutation – synonymous or nonsynonymous. SNPs shown in bold blue are the six SNPs in the top left corner of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002421#pone-0002421-g005\" target=\"_blank\">Figure 5</a>, the ones most correlated with patterns enriched in the longevity group. Note that these are either non-specific or markers for haplogroup D4a. The locations 152 and 16129 are known mutational hotspots in the hypervariable regions HVS-II and HVS-I respectively and hence their correlation with longevity cannot be considered significant.</p>", "links"=>[], "tags"=>["mtsnps", "enhanced", "patterns", "semi-supercentenarians"], "article_id"=>600348, "categories"=>["Genetics"], "users"=>["Erhan Bilal", "Raul Rabadan", "Gabriela Alexe", "Noriyuki Fuku", "Hitomi Ueno", "Yutaka Nishigaki", "Yasunori Fujita", "Masafumi Ito", "Yasumichi Arai", "Nobuyoshi Hirose", "Andrei Ruckenstein", "Gyan Bhanot", "Masashi Tanaka"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002421.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_List_of_most_frequent_mtSNPs_from_enhanced_patterns_see_Figure_5_in_semi_supercentenarians_vs_healthy_normals_/600348", "title"=>"List of most frequent mtSNPs from enhanced patterns (see Figure 5) in semi-supercentenarians vs. healthy normals.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-06-11 00:05:48"}

PMC Usage Stats | Further Information

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Relative Metric

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