Human Genetics

, Volume 121, Issue 3, pp 347–356

Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population

Authors

  • Gabriela Alexe
    • The Broad Institute of MIT and Harvard
    • The Simons Center for Systems Biology, Institute for Advanced Study
  • Noriyuki Fuku
    • Department of Genomics for Longevity and HealthTokyo Metropolitan Institute of Gerontology
  • Erhan Bilal
    • BioMaPS InstituteRutgers University
  • Hitomi Ueno
    • Department of Genomics for Longevity and HealthTokyo Metropolitan Institute of Gerontology
  • Yutaka Nishigaki
    • Department of Genomics for Longevity and HealthTokyo Metropolitan Institute of Gerontology
  • Yasunori Fujita
    • Department of Longevity and Aging ResearchGifu International Institute of Biotechnology
  • Masafumi Ito
    • Department of Longevity and Aging ResearchGifu International Institute of Biotechnology
  • Yasumichi Arai
    • Department of Geriatric MedicineKeio University School of Medicine
  • Nobuyoshi Hirose
    • Department of Geriatric MedicineKeio University School of Medicine
    • The Simons Center for Systems Biology, Institute for Advanced Study
    • BioMaPS InstituteRutgers University
    • Department of Biomedical EngineeringRutgers University
    • Cancer Institute of New Jersey
    • Department of Genomics for Longevity and HealthTokyo Metropolitan Institute of Gerontology
Original Investigation

DOI: 10.1007/s00439-007-0330-6

Cite this article as:
Alexe, G., Fuku, N., Bilal, E. et al. Hum Genet (2007) 121: 347. doi:10.1007/s00439-007-0330-6

Abstract

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.

Supplementary material

439_2007_330_MOESM1_ESM.xls (1.2 mb)
Supplementary_Table_1. Binary matrix of mutations for all samples and their phenotypes showing all polymorphic loci with respect to rCRS. A non-mutated locus is represented by 0, a mutated locus by 1. Haplogroup assignments are also shown. We list both haplogroups assigned to the sample in the literature and the haplogroup from consensus ensemble clustering and bootstrap analysis. Binary table showing mutations with respect to rCRS for all samples, including phenotype labels. The phenotype labels are from Ref 10 and correspond to the following: JD: Diabetics with Angiopathy, ND: Diabetics without Angiopathy, HN: Healthy Normals, ON: Obese Normals, KA: Alzheimer's Disease Patients, PD: Parkinson's disease patients, TC/GC: Centenarians. (xls 1243 kb)

Copyright information

© Springer-Verlag 2007