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
N1 - Funding Information:
Acknowledgments This work was supported in part by Support Project for Database Development from the Japan Science and Technology Corporation (to M. T.), Grants-in-Aid for Scientific Research (C2-10832009, A2-15200051) and for Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan (to M. T.), and by grants BMC2001-3511 and COF2002-015 (to V. M. C.).
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.
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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 -