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

Gabriela Alexe, Noriyuki Fuku, Erhan Bilal, Hitomi Ueno, Yutaka Nishigaki, Yasunori Fujita, Masafumi Ito, Yasumichi Arai, Nobuyoshi Hirose, Gyan Bhanot, Masashi Tanaka

Research output: Contribution to journalArticle

51 Citations (Scopus)

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. At-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.

Original languageEnglish
Pages (from-to)347-356
Number of pages10
JournalHuman Genetics
Volume121
Issue number3-4
DOIs
Publication statusPublished - 2007 May

Fingerprint

Mitochondrial DNA
Phenotype
Population
Mitochondrial Genome
Parkinson Disease
Alzheimer Disease
Mutation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Alexe, G., Fuku, N., Bilal, E., Ueno, H., Nishigaki, Y., Fujita, Y., ... Tanaka, M. (2007). Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population. Human Genetics, 121(3-4), 347-356. https://doi.org/10.1007/s00439-007-0330-6

Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population. / Alexe, Gabriela; Fuku, Noriyuki; Bilal, Erhan; Ueno, Hitomi; Nishigaki, Yutaka; Fujita, Yasunori; Ito, Masafumi; Arai, Yasumichi; Hirose, Nobuyoshi; Bhanot, Gyan; Tanaka, Masashi.

In: Human Genetics, Vol. 121, No. 3-4, 05.2007, p. 347-356.

Research output: Contribution to journalArticle

Alexe, G, Fuku, N, Bilal, E, Ueno, H, Nishigaki, Y, Fujita, Y, Ito, M, Arai, Y, Hirose, N, Bhanot, G & Tanaka, M 2007, 'Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population', Human Genetics, vol. 121, no. 3-4, pp. 347-356. https://doi.org/10.1007/s00439-007-0330-6
Alexe, Gabriela ; Fuku, Noriyuki ; Bilal, Erhan ; Ueno, Hitomi ; Nishigaki, Yutaka ; Fujita, Yasunori ; Ito, Masafumi ; Arai, Yasumichi ; Hirose, Nobuyoshi ; Bhanot, Gyan ; Tanaka, Masashi. / Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population. In: Human Genetics. 2007 ; Vol. 121, No. 3-4. pp. 347-356.
@article{d14ff9c9e0a048ae9a60f76bf0fff484,
title = "Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population",
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. At-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.",
author = "Gabriela Alexe and Noriyuki Fuku and Erhan Bilal and Hitomi Ueno and Yutaka Nishigaki and Yasunori Fujita and Masafumi Ito and Yasumichi Arai and Nobuyoshi Hirose and Gyan Bhanot and Masashi Tanaka",
year = "2007",
month = "5",
doi = "10.1007/s00439-007-0330-6",
language = "English",
volume = "121",
pages = "347--356",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "3-4",

}

TY - JOUR

T1 - Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population

AU - Alexe, Gabriela

AU - Fuku, Noriyuki

AU - Bilal, Erhan

AU - Ueno, Hitomi

AU - Nishigaki, Yutaka

AU - Fujita, Yasunori

AU - Ito, Masafumi

AU - Arai, Yasumichi

AU - Hirose, Nobuyoshi

AU - Bhanot, Gyan

AU - Tanaka, Masashi

PY - 2007/5

Y1 - 2007/5

N2 - 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. At-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.

AB - 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. At-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.

UR - http://www.scopus.com/inward/record.url?scp=34147166646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147166646&partnerID=8YFLogxK

U2 - 10.1007/s00439-007-0330-6

DO - 10.1007/s00439-007-0330-6

M3 - Article

C2 - 17308896

AN - SCOPUS:34147166646

VL - 121

SP - 347

EP - 356

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 3-4

ER -