Biomarker Validation for Aging: Lessons from mtDNA Heteroplasmy Analyses in Early Cancer Detection

Biomarker Insights

Volumn 4, Issue , 2009, Pages

  Barker, Peter E ^a   Murthy, Mahadev ^b  

^a NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY   (United States)

^b NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

aging; biomarker; cancer; early cancer detection; economic impact; healthcare; heteroplasmy; mitochondrial DNA (mtDNA) sequencing; mitochondriome; mutation; next generation DNA sequencing (NGS); reactive oxygen species (ROS); surface enhanced laser desorption ionization based mass spectrometry (SELDI MS); technology; validation

Indexed keywords

EID: 79956297148     PISSN: None     EISSN: 11772719     Source Type: Journal    
DOI: 10.4137/BMI.S2253     Document Type: Review

References (148)

1. Sidransky D. Emerging molecular markers of cancer. Nat Rev Cancer 2002; 235: 247–63.
2. Etzioni R., Urban N., Ramsey S. et al. The case for early detection. Nat Rev Cancer. 2003; 3(4): 243–52.
3. Block T.M., Marrero J., Gish R.G. et al. The degree of readiness of selected biomarkers for the early detection of hepatocellular carcinoma: notes from a recent workshop. Cancer Biomark. 2008; 4(1): 19–33.
4. Hartwell L.H., Szankasi P., Roberts C.J., Murray A.W., Friend S.H. Integrating genetic approaches into the discovery of anticancer drugs. Science. 1997; 278(5340): 1064–8.
5. Lee J.W., Devanarayan V., Barrett Y.C. et al. Fit-for-purpose method development and validation for successful biomarker measurement. Pharm Res. 2006; 23(2): 312–28.
6. Williams S.A., Slavin D.E., Wagner J.A., Webster C.J. A cost-effectiveness approach to the qualification and acceptance of biomarkers. Nature Rev Drug Discovery. 2006; 5: 897–902.
7. Altar C.A., Amakye D., Bounos D. et al. A prototypical process for creating evidentiary standards for biomarkers and diagnostics. Clin Pharmacol Ther. 2008; 83(2): 368–71.
8. Ransohoff D.F. The process to discover and develop biomarkers for cancer: a work in progress. J Natl Cancer Inst. 2008; 100(20): 1419–20.
9. Pepe M.S., Feng Z., Janes H., Bossuyt P.M., Potter J.D. Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design. J Natl Cancer Inst. 2008; 100(2): 1432–8.
10. Pepe M.S., Etzioni R., Feng Z. et al. Phases of biomarker development for early detection of cancer. J Natl Cancer Inst. 2001; 93(14): 1054–10.
11. Food and Drug Administration, HHS. International conference on harmonization: guidance on E15 pharmacogenomics definitions and sample coding. Fed Regist. 2008; 73(68): 19074–6.
12. Gutman S., Hackett J. Search for shortcuts on the critical path to market: U.S. FDA perspectives from the diagnostic side. Pharmacogenomics. 2006; 7(8): 1223–7.
13. McLerran D., Grizzle W.E., Feng Z. et al. Analytical validation of serum proteomic profiling for diagnosis of prostate cancer: sources of sample bias. Clin Chem. 2008a; 54(1): 44–52. Epub 2007 Nov 2.
14. McLerran D., Grizzle W.E., Feng Z. et al. SELDI-TOF MS whole serum proteomic profiling with IMAC surface does not reliably detect prostate cancer. Clin Chem. 2008b; 54(1): 53–60.
15. Tassey G. Planning Report 07-1 Economic analysis of the technology infrastructure needs of the U.S. biopharmaceutical industry (November 2007) NIST. 2007. http://www.nist.gov/director/planning/planning.htm.
16. Vaught J.B. Biorepository and biospecimen science: a new focus for CEBP. Cancer Epidemiol Biomarkers Prev. 2006; 15: 1572–3.
17. Robb J.A., Moore H.M., Compton C.C. Documenting biospecimen conditions in reports of studies. JAMA. 2008; 300(6): 650–1.
18. International Longevity Center Workshop. Biomarkers of aging: from primitive organisms to man. Interdisciplinary Workshop Report October 5–8, 2000, Tucson.
19. Ingram D.K., Nakamura E., Smucny D., Roth G.S., Lane M.A. Strategy for identifying biomarkers of aging in long-lived species. Exp Gerontol. 2001; 36: 1025–34.
20. Butler R.N., Sprott R., Warner H. et al. Biomarkers of aging: from primitive organisms to humans. J Gerontol A Biol Sci Med Sci. 2004; 59(6): B560–7.
21. Johnson T.E. Recent results: biomarkers of aging. Exp Gerontol. 2006; 41: 1243–6.
22. Simm A., Nass N., Bartling B., Hofmann B., Silber R.E., Santos N. Potential biomarkers of ageing. Biol Chem. 2008; 389: 257–65.
23. Vijg J., Campisi J. Puzzles, promises and a cure for ageing. Nature. 2008; 454(7208): 1065–71.
24. Campisi J., d'Adda di Fragagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007; 8: 729–40.
25. Cevenini E., Invidia L., Lescai F. et al. Human models of aging and longevity. Expert Opin Biol Ther. 2008; 8(9): 1393–405.
26. Golden T.R., Hubbard A., Dando C., Herren M.A., Melov S. Age-related behaviors have distinct transcriptional profiles in C. elegans. Aging Cell. 2008 Sep 5, [Epub ahead of print].
27. Clancy D.J. Variation in mitochondrial genotype has substantial lifespan effects which may be modulated by nuclear background. Aging Cell. 2008 Aug 21, [Epub ahead of print].
28. McCay C.M., Crowell M.F., Maynard L.A. The effect of retarded growth upon the life span and upon ultimate body side. J Nutr. 1935; 10: 63–79.
29. Weindruch R., Walford R.L. The Retardation of Aging and Disease By Dietary Restriction; Springfield, Ill: Charles C Thomas. 1988.
30. Harper J.M., Leathers C.W., Austad S.N. Does caloric restriction extend life span in wild mice? Aging Cell. 2006; 5: 441–9.
31. Heydari A.R., Unnikrishnan A., Lucente L.V., Richardson A. Caloric restriction and genomic stability. Nuc Acids Res. 2007; 35: 7485–96.
32. Shimokawa I., Chiba T., Yamaza H., Komatsu T. Longevity genes: insights from caloric restriction and genetic longevity models. Mol Cells 2008; 26: 427–35.
33. Barger J.L., Kayo T., Vann J.M. et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLOS One. 2008; 3(6): e2264.
34. Chen D., Guarente L. SIR2: a potential target for calorie restriction mimetics. Trends Mol Med. 2007; 13(2): 64–71.
35. Vijg J., Maslov A.Y., Suh Y. Aging: a sirtuin shake-up? Cell. 2008; 135(5): 797–8.
36. Oberdoerffer P., Michan S., McVay M. et al. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell. 2008; 135(5): 907–18.
37. Ransohoff D.F. Lessons from controversy: ovarian cancer screening and serum proteomics. J Natl Cancer Inst. 2005; 97(4): 315–9.
38. Ransohoff D.F. How to improve reliability and efficiency of research about molecular markers: roles of phases, guidelines, and study design. J Clin Epidemiol. 2007; 60(12): 1205–19.
39. Baker G.T., Sprott R.L. Biomarkers of aging. Exp Gerontol. 1988; 23: 223–39.
40. Manolio T.A., Brooks L.D., Collins F.S. A HapMap harvest of insights into the genetics of common disease. J Clin Invest. 2008; 118(5): 1590–605.
41. Kidd J.M., Cooper G.M., Donahue W.F. et al. Mapping and sequencing of structural variation from eight human genomes. Nature. 2008; 453(7191): 56–64.
42. Kruse U., Bantscheff M., Drewes G., Hopf C. Chemical and pathway proteomics: Powerful tools for oncology drug discovery and personalized health care. Mol Cell Proteomics. 2008 Aug 1.
43. Fiehn O. Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks. Comp Funct Genomics. 2001; 2(3): 155–68.
44. Wishart D.S. Applications of metabolomics in drug discovery and development. Drugs R D. 2008; 9(5): 307–22.
45. Barker P.E., Wagner P.D., Stein S.E., Bunk D.M., Srivastava S., Omenn G.S. Standards for plasma and serum proteomics in early cancer detection: A needs assessment report from the NIST-NCI SMART Workshop, August 18–19, 2005. Clin Chem. 2006; 52(9): 1669–74.
46. Cotton R.G., Appelbe W., Auerbach A.D. et al. Recommendations of the 2006 Human Variome Project Meeting. Nat Gen. 2006; 39: 433–6.
47. Bubnoff A. Next-generation sequencing: the race is on. Cell. 2008; 132: 721–3.
48. Kitano H. Computational systems biology. Nature. 2002; 420: 206–10.
49. Kirkwood T.B. A systematic look at an old problem. Nature. 2008; 451: 644–7.
50. Baker D.J., Jin F., van Duersen J.M. The yin and yang of Cdkn2a locus in senescence and aging. Cell Cycle. 2008; 7(18). Epub September 28.
51. Berryman D.E., Christiansen J.S., Johannsson G., Thorner M.O., Kopchick J.J. Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models. Growth Hormone IGF Res. 2008, Aug 16.
52. Jiang H., Schiffer E., Song Z. et al. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. Proc Natl Acad Sci USA. 2008; 105(32): 11299–304.
53. Kujoth G.C., Hiona A., Pugh T.D. et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 2005; 309(5733): 481–4.
54. Loeb L.A., Wallace D.C., Martin G.M. The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations. Proc Natl Acad Sci USA. 2005; 102(52): 18769–70.
55. Trifunovic A. Mitochondrial DNA and ageing. Biochim Biophys Acta. 2006; 1757: 611–7.
56. Bonawitz N.D., Shadel G.S. Rethinking the mitochondrial theory of aging: the role of mitochondrial gene expression in lifespan determination. Cell Cycle. 2007; 6(13): 1574–8.
57. Vermulst M., Bielas J.H., Kujoth G.C. et al. Mitochondrial point mutations do not limit the natural lifespan of mice. Nat Genet. 2007; 39: 540–3.
58. Fukui H., Moraes C.T. The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis? Trends Neurosci. 2008; 31(5): 251–6.
59. Polyak K., Li Y., Zhu H. et al. Somatic mutations of the mitochondrial genome in human colorectal tumors. Nature Genet. 1998; 20: 291–3.
60. Fliss M.S., Usadel H., Caballero O.L. et al. Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science. 2001; 287(5460): 2017–9.
61. Bragoszewski P., Kupryjanczyk J., Bartnik E., Rachinger A., Ostrowski J. Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer. BMC Cancer. 2008; 8: 292.
62. Risch A., Plass C. Lung cancer epigenetics and genetics. Int J Cancer. 2008; 123(1): 1–7.
63. Yung R.L., Julius A. Epigenetics, aging, and autoimmunity. Autoimmunity. 2008; 41(4): 329–35.
64. Kagan J., Srivastava S., Barker P.E., Belinsky S.A., Cairns P. Towards clinical application of methylated DNA sequences as cancer biomarkers: a joint NCI's EDRN and NIST workshop on standards, methods, assays, reagents and tools (SMART). Cancer Research. 2007; 67(10): 4545–9.
65. Anderson S., Bankier A.T., Barrell B.G. et al. Sequence and organization of the human mitochondrial genome. Nature. 1981; 290: 457–65.
66. Andrews R.M., Kubacka I., Chinnery P.F., Lightowlers R.N., Turnbull D.M., Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet. 1999; 23: 147.
67. Hauswirth W.W., Laipis P.J. Mitochondrial DNA polymorphism in a maternal lineage of Holsetin cows. Proc Natl Acad Sci USA. 1982; 79: 4686–90.
68. Michaels G.S., Hauswirth W.W., Laipis P.J. Mitochondrial DNA copy numbers in bovine oocytes and somatic cells. Dev Biol. 1982; 57: 246–51.
69. Pinto D., Marshall C., Feuk L., Scherer S.W. Copy-number variation in control population cohorts. Hum Mol Genet. 2007; 16(Spec No 2): R168–73.
70. Lee J.A., Lupski J.R. Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders. Neuron. 2006; 52(1): 103–21.
71. Kroemer G., Pouyssegur J. Tumor cell metabolism: cancer's Achilles heel. Cancer Cell. 2008; 13: 472–82.
72. Ow Y.L., Green D.R., Hao Z., Mak T.W. Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol. 2008; 9: 532–42.
73. Pagliarini D.J., Calvo S.E., Chang B. et al. A mitochondrial protein compendium elucidates complex I disease biology. Cell. 2008; 134(1): 112–23.
74. King M.P., Attardi G.A. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science. 1989; 246: 500–3.
75. Kukat A., Kukat C., Brocher J. et al. Generation of p0 cells utilizing a mitochondrially targeted restriction endonuclease and comparative analyses. Nuc Acids Res. 2008; 36(7): e44.
76. Xu H., DeLuca S.Z., O'Farrell P.H. Manipulating the metazoan mitochondrial genome with targeted restriction enzymes. Science. 2008; 321: 575–7.
77. Giles R.E., Blanc H., Cann H., Wallace D.C. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci USA. 1980; 77(11): 5715–6719.
78. Sutovsky P., Schatten G. Paternal contributions to the mammalian zygote: fertilization after sperm-egg fusion. Int Rev Cytol. 2000; 195: 1–65.
79. Wallace D.C. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Ann Rev Genet. 2005; 39: 359–407.
80. Sutovsky P., Moreno R.D., Ramalho-Santos J., Dominko T., Simerly C., Schatten G. Ubiquitinated sperm mitochondria, selective proteolysis, and the regulation of mitochondrial inheritance in mammalian embryos. Biol Reprod. 2000; 63(2): 582–90.
81. Shitara H., Hayashi J.I., Takahama S., Kaneda H., Yonekawa H. Maternal inheritance of mouse mtDNA in interspecific hybrids: segregation of the leaked paternal mtDNA followed by prevention of subsequent paternal leakage. Genetics. 1998; 148: 851–7.
82. Cao L., Shitara H., Horii T. et al. The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells. Nat Genet. 2007; 39(3): 386–90. Epub 2007 Feb 11.
83. Cree L.M., Samuels D.C., de Sousa Lopes S.C. et al. A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat Genet. 2008; 40(2): 249–54.
84. Nomura Y., Fuchigami H., Kii H., Feng Z., Nakamura T., Kinjo M. Detection of oxidative stress-induced mitochondrial DNA damage using fluorescence correlation spectroscopy. Anal Biochem. 2006; 350: 196–201.
85. Legros F., Malka F., Frachon P., Lombes A., Rojo M. Organization and dynamics of human mitochondrial DNA. J Cell Sci. 2004; 117: 2653–62.
86. Bogenhagen D.F., Rousseau D., Burke S. The layered structure of human mitochondrial nucleoids. J Biol Chem. 2007; 283(6): 3665–4054.
87. Gilkerson R.W., Schon E.A., Hernandez E., Davidson M.M. Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation. J Cell Biol. 2008; 181: 1117–28.
88. Rose G., Passarino G., Scornaienchi V. et al. The mitochondrial DNA control region shows genetically correlated levels of heteroplasmy in leukocytes of centenarians and their offspring. BMC Genomics. 2007; 8: 293–303.
89. Xing J., Chen M., Wood C.G. et al. Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma. J Natl Acad Sci. 2008; 100: 1104–12.
90. Niemi A.K., Hervonen A., Hurme M., Kurhunen P.J., Jylha M., Majamaa K. Mitochondrial DNA polymorphisms associated with longevity in a Finnish population. Human Genetics. 2002; 112: 29–33.
91. Dato S., Passarino G., Rose G. et al. Association of the mitochondrial DNA haplogroups J with longevity is population specific. Eur J Human Genet. 2004; 12: 1080–2.
92. Yao Y.G., Ellison F.M., McCoy J.P., Chen J., Young N.S. Age-dependent accumulation of mtDNA mutations in murine hematopoietic stem cells is modulated by the nuclear genetic background. Hum Mol Genet. 2007; 16(3): 286–94.
93. Petricoin E.F., Ardekani A.M., Hitt B.A. et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002; 359(9306): 572–7.
94. Cazares L.H., Diaz J.I., Drake R.R., Semmes O.J. MALDI/SELDI protein profiling of serum for the identification of cancer biomarkers. Methods Mol Biol. 2008; 428: 125–40.
95. Baggerly K., Morris J.S., Coombs K.R. Reproducibility of SELDI-TOF protein patterns in serum: comparing datasets from different experiments. Bioinformatics. 2005; 20: 777–85.
96. Levin B.C., Cheng H., Reeder D.J. A human mitochondrial DNA Standard Reference Material for quality control in forensic identification, medical diagnosis, and mutation detection. Genomics. 1999; 55: 135–46.
97. Andréasson H., Nilsson M., Budowle B., Lundberg H., Allen M. Nuclear and mitochondrial DNA quantification of various forensic materials. Forensic Sci Int. 2006; 164(1): 56–64.
98. Budowle B., van Daal A. Forensically relevant SNP classes. Biotechniques. 2008; 44(5): 603–8, 610.
99. Green R.E., Malaspinas A.S., Krause J. et al. A complete neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell. 2008; 134(3): 416–26.
100. Cortopassi G.A., Shibata D., Soong N.W., Arnheim N. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA. 1992; 89: 7370–4.
101. Tan D., Goerlitz D.S., Dumitrescu R.G. et al. Associations between cigarette smoking and mitochondrial DNA abnormalities in buccal cells. Carcinogenesis. 2008; 29(6): 1170–7. Epub 2008 Feb 14.
102. Salas A., Carracedo A., Macaulay V., Richards M., Bandelt H.J. A practical guide to mitochondrial DNA error prevention in clinical, forensic, and population genetics. Biochem Biophys Res Commun. 2005; 335(3): 891–9.
103. Bandelt H.J., Salas A., Bravi C.M. What is a ‘novel’ mtDNA mutation—and does ‘novelty’ really matter? J Hum Genet. 2006; 51: 1073–82.
104. Kong Q.P., Salas A., Sun C. et al. Distilling artificial recombinants from large sets of complete mtDNA genomes. PLoS ONE. 2008; 3(8): e3016.
105. Lascaro D., Castellana S., Gasparre G., Romeo G., Saccone C., Attimonelli M. The RHNumtS compilation: features and bioinformatics approaches to locate and quantify human NumtS. BMC Genomics. 2008; 9: 267.
106. Yao Y.G., Kong Q.P., Salas A., Bandelt H.J. Pseudo-mitochondrial genome haunts disease studies. J Med Genet. 2008 Jul 8. [Epub ahead of print].
107. Lopez J.V., Yuhki N., Masuda R., Modi W., O'Brien S.J. Numt, a recent transfer and tandem amplification of mitochondrial DNA to the nuclear genome of the domestic cat. J Mol Evol. 1994; 39(2): 174–90.
108. Melov S., Hinerfeld D., Esposito L., Wallace D.C. Multi-organ characterization of mitochondrial genomic rearrangements in ad libitum and caloric restricted mice show striking somatic mitochondrial DNA rearrangements with age. Nuc Acids Res. 1997; 25: 974–82.
109. Bayona-Bafaluy M.P., Acin-Pérez R., Mullikin J.C. et al. Revisiting the mouse mitochondrial DNA sequence. Nuc Acids Res. 2003; 31(18): 5349–55.
110. Goios A., Pereira L., Bogue M., Macaulay V., Amorim A. mtDNA phylogeny and evolution of laboratory mouse strains. Genome Res. 2007; 17: 293–8.
111. Frazer K.A., Eskin E., Kang H.M. et al. A sequence-based variation map of 8.27 million SNPs in inbred mouse strains. Nature. 2007; 448: 1050–3.
112. Ingman M., Gyllensten U. mtDB: Human Mitochondrial Genome Database, a resource for population genetics and medical sciences. Nucleic Acids Res. 2006; 34: D749–51.
113. Hartmann A., Thieme M., Nanduri L.K. et al. Validation of microarray-based resequencing of 93 worldwide mitochondrial genomes. Hum Mutat. 2008; 30(1): 115–22.
114. Mouse Phenome Database, www.jax.org/phenome.
115. Sachadyn P., Zhang X.M., Clark L.D., Naviaux R.K., Heber-Katz E. Naturally occurring mitochondrial DNA heteroplasmy in the MRL mouse. Mitochondrion. 2008; 8: 358–65.
116. Tanhauser S.M., Laipis P.J. Multiple deletions are detectable in mitochondrial of aging mice. J Biol Chem. 1995; 270(42): 24769–75.
117. Kadenbach B., Muenscher C., Frank V., Mueller-Hoecker J., Napiwotski J. Human aging is associated with stochastic somatic mutations of mitochondrial DNA. Mutat Res. 1995; 338: 161–72.
118. Krishnan K.J., Greaves L.C., Reeve A.K., Turnbull D. The ageing mitochondrial genome. Nuc Acids Res. 2007; 35(22): 7399–405.
119. Corral-Debrinski M., Horton T., Lott M.T., Shoffner J.M., Beal M.F., Wallace D.C. Mitochondrial deletions in human brain: regional variability and increase with advanced age. Nat Genet. 1992; 2: 318–23.
120. Kang C.M., Kristal B.S., Yu B.P. Age-related mitochondrial DNA deletions: effect of dietary restriction. Free Radic Biol Med. 1998; 24(1): 148–54.
121. Chinnery P.F., Samuels D.C., Elson J., Turnbull D.M. Accumulation of DNA mutations in ageing, cancer and mitochondrial disease. Is there a common mechanism? Lancet. 2002; 360: 1323–5.
122. Prolla T. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 2005; 309(5733): 481–4.
123. Tyynismaa H., Mjosund K.P., Wanrooij S. et al. Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. Proc Natl Acad Sci USA. 2005; 102(49): 17687–92.
124. Zeviani M., Moraes C.T., DiMauro S. et al. Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology. 1988; 38: 1339–46.
125. Maki J., Robinson K., Reguly B. et al. Mitochondrial genome deletion aids in the identification of false- and true-negative prostate needle core biopsy specimens. Am J Clin Pathol. 2008; 129(1): 57–66.
126. Jakupciak J.J., Wang W., Markowitz M.E. et al. Mitochondrial DNA as a cancer biomarker. J Molec Diagn. 2005; 7(2): 258–67.
127. Yoon K.L., Modica-Napolitano J.S., Ernst S.G., Aprille J.R. Denaturing gradient gel method for mapping single base changes in human mitochondrial DNA. Anal Biochem. 1991; 196: 427–32.
128. Tully L.A. Examination of the use of forensic DNA typing from two perspectives I. Mitochondrial DNA heteroplasmy and II. The role of DNA typing in criminal investigations. Ph.D. Dissertation, University of Maryland Baltimore. 1998.
129. Tully L.A., Parsons T.J., Steighner R.J., Holland M.M., Marino M.A., Prenger V.L. A sensitive denaturing gradient gel electrophoresis assay reveals a high frequency of heteroplasmy in hypervariable region 1 of the human mtDNA control region. Am J Hum Genet. 2000; 67: 432–43.
130. Hancock D.K., Tully L.A., Levin B.C. A standard reference material to determine the sensitivity of techniques for detection of low-frequency mutations, SNPs, and heteroplasmies in mitochondrial DNA. Genomics. 2005; 86: 446–61.
131. Van den Bosch B.J., de Coo R.F., Scholte H.R. et al. Mutation analysis of the entire mitochondrial genome using denaturing high performance liquid chromatography. Nucl Acids Res. 2000; 28: E89.
132. Ballana E., Govea N., de Cid R. et al. Detection of unrecognized low-level mtDNA heteroplasmy may explain the variable phenotypic expressivity if apparently homoplasmic mtDNA mutations. Hum Mutat. 2008; 29: 248–57.
133. Levin B.C., Hancock D.K., Holland K.A., Cheng H., Richie K.L. Human mitochondrial DNA-amplification and sequencing-Standard Reference Materials SRM 2393 and 2393-I. NIST Special Publication. 2003; 260–165.
134. Maitra A., Cohen Y., Gillespie S.E. et al. The Human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection. Genome Res. 2004; 14(5): 812–9.
135. Zhou S., Kassauei K., Cutler D.J. et al. An oligonucleotide microarray for high-throughput sequencing of the mitochondrial genome. J Mol Diagn. 2006; 8(4): 476–82.
136. Jakupciak J.P., Maragh S., Markowitz M.E. et al. Performance of mitochondrial DNA mutations detecting early stage cancer. BMC Cancer. 2008; 8(1): 285.
137. Schones D.E., Cui K., Cuddapah S. et al. Dynamic regulation of nucleosome positioning in the human genome. Cell. 2008; 132(5): 887–98.
138. Poe B.G., Navratil M., Arriaga E.A. Absolute Quantitation of a heteroplasmic mitochondrial DNA deletion using a multiplex three-primer real-time PCR assay. Anal Biochem. 2006; 362: 193–200.
139. Hoeschle D., Wiertz M., Morena I.G. A duplex real-time PCR assay for detection of drug-induced mitochondrial depletion in HepG2 cells. Anal Biochem. 2008; 379: 70–2.
140. Dellinger M., Geze M. Detection of mitochondrial DNA in living animal cells with fluorescence microscopy. J Microscop. 2001; 204: 196–202.
141. Ashley N., Harris D., Poulton J. Detection of mitochondrial DNA depletion in living human cells using PicoGreen staining. Exp Cell Res. 2005; 303(2): 432–46.
142. Zullo S.J. In situ PCR of the common human mtDNA deletion. Is it related to apoptosis? Methods Mol Biol. 2002; 197: 119–28.
143. Mueller-Hoecker J., Seibel P., Schneiderbanger K., Kadenbach B. Different in situ hybridization patterns of mitochondrial DNA in cytochrome c oxidase-deficient extraocular muscle fibers in the elderly. Virchows Arch. A-Pathol. Anat Histopathol. 1993; 422: 7–15.
144. Janes M.S., Hanson B.J., Hill D.M. et al. Rapid analysis of mitochondrial DNA depletion by fluorescence in situ hybridization and immunocytochemistry: potential strategies for HIV therapeutic monitoring. J Histochem Cytochem. 2004; 52(8): 1011–8.
145. Van de Corput M.P.C., van den Ouweland J.M.W., Dirks R.W. et al. Detection of mitochondrial deletions in human skin fibroblasts of patients with Pearson's syndrome with two-color fluorescence in situ hybridization. J Histochem Cytochem. 1997; 45: 55–61.
146. Larsson C., Koch J., Nygren A. et al. In situ genotyping individual DNA molecules by target-primed rolling-circle amplification of padlock probes. Nat Methods. 2004; 1(3): 227–32.
147. Barker P.E. Cancer biomarker validation, standards and process: roles for the National Institute of Standards and Technology. Ann NY Acad Sci. 2003; 983: 142–150.
148. Tam W. The emergent role of microRNAs in molecular diagnostics of cancer. J Molec Diag. 2008; 10: 411–4.