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Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-05-1724. This Article Full Text (PDF) All Versions of this Article: 2003-05-1724v1 103/2/553    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shin, M. G Articles by Young, N. S Search for Related Content PubMed PubMed Citation Articles by Shin, M. G Articles by Young, N. S Social Bookmarking                   What's this? Submitted May 29, 2003 Accepted September 11, 2003 Marked mitochondrial DNA sequence heterogeneity in single CD34+ cell clones from normal adult bone marrow Myung G Shin, Sachiko Kajigaya, J P McCoy, Jr, Barbara C Levin, and Neal S Young* Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA Flow Cytometry Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA Chemical Science and Technology Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, USA * Corresponding author; email: youngn{at}nhlbi.nih.gov. Somatic mitochondrial DNA (mtDNA) mutations accumulate with age in postmitotic tissues but have been postulated to be diluted and lost in continually proliferating tissues such as bone marrow (BM). Having observed marked sequence variation among normal individuals' total BM cell mtDNA, we undertook to analyze the mtDNA control region in a total of 611 individual CD34+ clones from six adult BM donors and to compare these results with the sequences from 580 CD34+ clones from five umbilical cord blood (CB) samples. On average, twenty-five percent (11-50%) of individual CD34+ clones from adult BM showed mtDNA heterogeneity, or sequence differences from the aggregate mtDNA sequence of total BM cells of the same individual. In contrast, only 1.6% of single CD34+ clones from CB showed mtDNA sequence variation from the aggregate pattern. Thus, age-dependent accumulation of mtDNA mutations appears relatively common in a mitotically active human tissue and may provide a method to approximate the mutation rate in mammalian cells, to assess the contribution of reactive oxygen species to genomic instability, and for natural 'marking' of hematopoietic stem cells; our data also have important implications for the aging process, forensic identifications and anthropological conclusions dependent on the mtDNA sequence. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H.-W. Park, Y. Ahn, M.-H. Jeong, J.-G. Cho, J.-C. Park, J.-C. Kang, M.-G. Shin, J.-H. Shin, S.-P. Suh, D.-W. Ryang, et al. Chronic atrial fibrillation associated with somatic mitochondrial DNA mutations in human atrial tissue J. Clin. Pathol., August 1, 2007; 60(8): 948 - 950. [Full Text] [PDF] S. Lee, M.-G. Shin, W.-H. Jo, M.-J. Kim, H.-R. Kim, W.-S. Lee, D.-H. Park, J.-H. Won, J.-H. Shin, S.-P. Suh, et al. Association between Helicobacter pylori-Related Peptic Ulcer Tissue and Somatic Mitochondrial DNA Mutations Clin. Chem., July 1, 2007; 53(7): 1390 - 1392. [Full Text] [PDF] Y.-G. Yao, F. M. Ellison, J. P. McCoy, J. Chen, and N. S. Young Age-dependent accumulation of mtDNA mutations in murine hematopoietic stem cells is modulated by the nuclear genetic background Hum. Mol. Genet., February 1, 2007; 16(3): 286 - 294. [Abstract] [Full Text] [PDF] Y.-G. Yao, Y. Ogasawara, S. Kajigaya, J. J. Molldrem, R. P. Falcao, M.-C. Pintao, J. P. McCoy Jr, E. G. Rizzatti, and N. S. Young Mitochondrial DNA sequence variation in single cells from leukemia patients Blood, January 15, 2007; 109(2): 756 - 762. [Abstract] [Full Text] [PDF] H-J Bandelt, Q-P Kong, W Parson, and A Salas More evidence for non-maternal inheritance of mitochondrial DNA? J. Med. Genet., December 1, 2005; 42(12): 957 - 960. [Abstract] [Full Text] [PDF] Y. Ogasawara, K. Nakayama, M. Tarnowka, J. P. McCoy Jr, S. Kajigaya, B. C. Levin, and N. S. Young Mitochondrial DNA spectra of single human CD34+ cells, T cells, B cells, and granulocytes Blood, November 1, 2005; 106(9): 3271 - 3284. [Abstract] [Full Text] [PDF] M. G. Shin, S. Kajigaya, M. Tarnowka, J. P. McCoy Jr, B. C. Levin, and N. S. Young Mitochondrial DNA sequence heterogeneity in circulating normal human CD34 cells and granulocytes Blood, June 15, 2004; 103(12): 4466 - 4477. [Abstract] [Full Text] [PDF]

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