Heteroplasmy levels of a mitochondrial gene mutation associated with diabetes mellitus decrease in leucocyte DNA upon aging

Hum Mutat. 1996;7(3):193-7. doi: 10.1002/(SICI)1098-1004(1996)7:3<193::AID-HUMU2>3.0.CO;2-C.


We showed previously that a mutation in the mitochondrial tRNALeu(UUR) gene at position 3243 associates with maternally inherited diabetes and deafness (MIDD). This mutation shows heteroplasmy in DNA from peripheral blood and other tissues. To examine whether heteroplasmy levels in peripheral blood DNA change upon aging, heteroplasmy levels were determined in DNA samples from peripheral blood, collected recently and 1.5-6 years ago, from 18 individuals carrying the 3243 mutation. It was found that 17 out of 18 carriers showed a decrease upon aging (P = 0.001), the average change being -0.69 +/- 0.61% per year. These data indicate a continuous selection against haematopoietic (precursor) cells carrying high levels of the 3243 mutation. Moreover, they imply that heteroplasmy levels may decrease below the detection limit if DNA from peripheral blood is analyzed from elderly individuals. DNA from oral mucosa cells was found to be a good alternative as heteroplasmy levels for the 3243 mutation are on the average 1.7 fold higher than in DNA from peripheral blood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aging*
  • Blotting, Southern
  • DNA, Mitochondrial / blood
  • DNA, Mitochondrial / genetics*
  • Diabetes Mellitus / genetics*
  • Female
  • Hematopoietic Stem Cells / chemistry
  • Humans
  • Leukocytes / chemistry
  • Male
  • Middle Aged
  • Pedigree
  • Point Mutation*
  • Polymerase Chain Reaction
  • RNA, Transfer, Leu / genetics*
  • Statistics, Nonparametric


  • DNA, Mitochondrial
  • RNA, Transfer, Leu