Issue
Quantification of circadian rhythm in mitochondrial DNA copy number in whole blood, and identification of factors that influence it
Corresponding Author(s) : Junjie Luo
Cellular and Molecular Biology,
Vol. 66 No. 5: Issue 5
Abstract
Mitochondrial DNA (mtDNA), the genetic material in mitochondria, encodes key genes related to the respiratory chain and ATP production. To accurate quantification mtDNA content in whole blood is important for various disease states. Absolute quantitative Real-time PCR and platelet contamination erase method were used for mtDNA copy number analysis in whole blood. In the quantitative study of mtDNA content, it was found that whole blood mtDNA copy number showed a fluctuating rhythm during a 24-h period due to dynamic changes in white blood cells combined with platelets. However, when isolated white blood cells were used, or absolute whole blood mtDNA was calculated, the circadian rhythm pattern of mtDNA disappeared. In this study, a feasible method that can accurately quantify mitochondrial DNA in small blood samples was established, and it was found that two factors which greatly influenced mtDNA copy number were sampling time and platelets in blood.
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- Giorgi C, Agnoletto C, Bononi A, Bonora M, De Marchi E, Marchi S, et al. Mitochondrial calcium homeostasis as potential target for mitochondrial medicine. Mitochondrion 2012; 12: 77-85.
- Lopez-Armada MJ, Riveiro-Naveira RR, Vaamonde-Garcia C, Valcarcel-Ares MN. Mitochondrial dysfunction and the inflammatory response. Mitochondrion 2013; 13: 106-118.
- Miller WL. Steroid hormone synthesis in mitochondria. Mol Cell Endocrinol 2013; 379: 62-73.
- Patterson HC, Gerbeth C, Thiru P, Vögtle NF, Knoll M, Shahsafaei A, et al. A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling. Proc Natl Acad Sci U S A 2015; 112: 5679-5688.
- Chandel NS. Evolution of Mitochondria as Signaling Organelles. Cell Metab 2015; 22: 204-206.
- Chandel NS. Mitochondria as signaling organelles. BMC Biol 2014; 12: 34.
- Wang C, Youle RJ. The role of mitochondria in apoptosis*. Annu Rev Genet 2009; 43: 95-118.
- Chistiakov DA, Shkurat TP, Melnichenko AA, Grechko AV, Orekhov AN. The role of mitochondrial dysfunction in cardiovascular disease: a brief review. Ann Med 2018; 50: 121-127.
- Ward MS, Fortheringham AK, Cooper ME, Forbes JM. Targeting advanced glycation endproducts and mitochondrial dysfunction in cardiovascular disease. Curr Opin Pharmacol 2013; 13: 654-661.
- Ballinger SW. Mitochondrial dysfunction in cardiovascular disease. Free Radic Biol Med 2005; 38: 1278-1295.
- Kokotas H, Petersen MB, Willems PJ. Mitochondrial deafness. Clin Genet 2007; 71: 379-391.
- Leishangthem BD, Sharma A, Bhatnagar A. Role of altered mitochondria functions in the pathogenesis of systemic lupus erythematosus. Lupus 2016; 25: 272-281.
- Smith EF, Shaw PJ, De Vos KJ. The role of mitochondria in amyotrophic lateral sclerosis. Neurosci Lett 2019; 710: 132933.
- Duffy LM, Chapman AL, Shaw PJ, Grierson AJ. Review: The role of mitochondria in the pathogenesis of amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 2011; 37: 336-352.
- Borthwick GM, Johnson MA, Ince PG, Shaw PJ, Turnbull DM. Mitochondrial enzyme activity in amyotrophic lateral sclerosis: implications for the role of mitochondria in neuronal cell death. Ann Neurol 1999; 46: 787-790.
- Siddiqui MF, Elwell C, Johnson MH. Mitochondrial Dysfunction in Autism Spectrum Disorders. Autism Open Access 2016;6: 1000190.
- Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 2012; 17: 290-314.
- Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet 1993; 4: 289-294.
- Meng F, He Z, Tang X, Zheng J, Jin X, Zhu Y, et al. Contribution of the tRNA(Ile) 4317A-->G mutation to the phenotypic manifestation of the deafness-associated mitochondrial 12S rRNA 1555A-->G mutation. J Biol Chem 2018; 293: 3321-3334.
- McFarland R, Schaefer AM, Gardner JL, Lynn S, Hayes CM, Barron MJ, et al. Familial myopathy: new insights into the T14709C mitochondrial tRNA mutation. Ann Neurol 2004; 55: 478-484.
- Hao H, Bonilla E, Manfredi G, DiMauro S, Moraes CT. Segregation patterns of a novel mutation in the mitochondrial tRNA glutamic acid gene associated with myopathy and diabetes mellitus. Am J Hum Genet 1995; 56: 1017-1025.
- Chen N, Wen S, Sun X, Fang Q, Huang L, Liu S, et al. Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis. Sci Rep 2016; 6: 37404.
- Tin A, Grams ME, Ashar FN, Lane JA, Rosenberg AZ, Grove ML, et al. Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study. J Am Soc Nephrol 2016; 27: 2467-2473.
- Lee JY, Lee DC, Im JA, Lee JW. Mitochondrial DNA copy number in peripheral blood is independently associated with visceral fat accumulation in healthy young adults. Int J Endocrinol 2014; 2014: 586017.
- Lee SH, Chung DJ, Lee HS, Kim TJ, Kim MH, Jeong HJ, et al. Mitochondrial DNA copy number in peripheral blood in polycystic ovary syndrome. Metabolism 2011; 60: 1677-1682.
- Zhang J, Xu S, Xu Y, Liu Y, Li Z, Zhang Y, et al. Relation of Mitochondrial DNA Copy Number in Peripheral Blood to Postoperative Atrial Fibrillation After Isolated Off-Pump Coronary Artery Bypass Grafting. Am J Cardiol 2017; 119: 473-477.
- Sun Y, Zhang L, Ho SS, Wu X, Gu J. Lower mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of endometrial cancer. Mol Carcinog 2016; 55: 1111-1117.
- 28. Tu H, Gu J, Meng QH, Kim J, Davis JW, He Y, et al. Mitochondrial DNA copy number in peripheral blood leukocytes and the aggressiveness of localized prostate cancer. Oncotarget 2015; 6: 41988-41996.
- Shen J, Gopalakrishnan V, Lee JE, Fang S, Zhao H. Mitochondrial DNA copy number in peripheral blood and melanoma risk. PLoS One 2015; 10: 131649.
- Melkonian SC, Wang X, Gu J, Matin SF, Tannir NM, Wood CG, et al. Mitochondrial DNA copy number in peripheral blood leukocytes and the risk of clear cell renal cell carcinoma. Carcinogenesis 2015; 36: 249-255.
- Lemnrau A, Brook MN, Fletcher O, Coulson P, Tomczyk K, Jones M, et al. Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer. Cancer Res 2015; 75: 2844-2850.
- Zhou W, Zhu M, Gui M, Huang L, Long Z, Wang L, et al. Peripheral blood mitochondrial DNA copy number is associated with prostate cancer risk and tumor burden. PLoS One 2014; 9: 109470.
- Xu E, Sun W, Gu J, Chow WH, Ajani JA, Wu X. Association of mitochondrial DNA copy number in peripheral blood leukocytes with risk of esophageal adenocarcinoma. Carcinogenesis 2013; 34: 2521-2524.
- Xie H, Lev D, Gong Y, Wang S, Pollock RE, Wu X, et al. Reduced mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of soft tissue sarcoma. Carcinogenesis 2013; 34: 1039-1043.
- Purdue MP, Hofmann JN, Colt JS, Hoxha M, Ruterbusch JJ, Davis FG, et al. A case-control study of peripheral blood mitochondrial DNA copy number and risk of renal cell carcinoma. PLoS One 2012; 7: 43149.
- Yoo HJ, Park M, Kim SA. Difference in mitochondrial DNA copy number in peripheral blood cells between probands with autism spectrum disorders and their unaffected siblings. World J Biol Psychiatry 2017; 18: 151-156.
- Chen S, Li Z, He Y, Zhang F, Li H, Liao Y, et al. Elevated mitochondrial DNA copy number in peripheral blood cells is associated with childhood autism. BMC Psychiatry 2015; 15: 50.
- He Y, Tang J, Li Z, Li H, Liao Y, Tang Y, et al. Leukocyte mitochondrial DNA copy number in blood is not associated with major depressive disorder in young adults. PLoS One 2014; 9: 96869.
- Pyle A, Anugrha H, Kurzawa-Akanbi M, Yarnall A, Burn D, Hudson G. Reduced mitochondrial DNA copy number is a biomarker of Parkinson's disease. Neurobiol Aging 2016; 38: 216.
- Sun J, Longchamps RJ, Piggott DA, Castellani CA, Sumpter JA, Brown TT, et al. Association Between HIV Infection and Mitochondrial DNA Copy Number in Peripheral Blood: A Population-Based, Prospective Cohort Study. J Infect Dis 2019; 219: 1285-1293.
- Yang Y, Yang J, Yu B, Li L, Luo L, Wu F, et al. Association between circulating mononuclear cell mitochondrial DNA copy number and in-hospital mortality in septic patients: A prospective observational study based on the Sepsis-3 definition. PLoS One 2019; 14: 212808.
- Lei L, Guo J, Shi X, Zhang G, Kang H, Sun C, et al. Mitochondrial DNA copy number in peripheral blood cell and hypertension risk among mining workers: a case-control study in Chinese coal miners. J Hum Hypertens 2017; 31: 585-590.
- Mengel-From J, Thinggaard M, Dalgard C, Kyvik KO, Christensen K, Christiansen L. Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly. Hum Genet 2014; 133: 1149-1159.
- Ashar FN, Zhang Y, Longchamps RJ, Lane J, Moes A, Grove ML, et al. Association of Mitochondrial DNA Copy Number With Cardiovascular Disease. JAMA Cardiol 2017; 2: 1247-1255.
- Abo T, Kawate T, Itoh K, Kumagai K. Studies on the bioperiodicity of the immune response. I. Circadian rhythms of human T, B, and K cell traffic in the peripheral blood. J Immunol 1981; 126: 1360-1363.
- Miyawaki T, Taga K, Nagaoki T, Seki H, Suzuki Y, Taniguchi N. Circadian changes of T lymphocyte subsets in human peripheral blood. Clin Exp Immunol 1984; 55: 618-622.
- Shuster RC, Rubenstein AJ, Wallace DC. Mitochondrial DNA in anucleate human blood cells. Biochem Biophys Res Commun 1988; 155: 1360-1365.
- Nemzek JA, Bolgos GL, Williams BA, Remick DG. Differences in normal values for murine white blood cell counts and other hematological parameters based on sampling site. Inflamm Res 2001; 50: 523-527.
- Bain BJ. Ethnic and sex differences in the total and differential white cell count and platelet count. J Clin Pathol 1996; 49: 664-666.
- Boudreau LH, Duchez AC, Cloutier N, Soulet D, Martin N, Bollinger J, et al. Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation. Blood 2014; 124: 2173-2183.
- Urata M, Koga-Wada Y, Kayamori Y, Kang D. Platelet contamination causes large variation as well as overestimation of mitochondrial DNA content of peripheral blood mononuclear cells. Ann Clin Biochem 2008; 45: 513-514.
- Banas B, Kost BP, Goebel FD. Platelets, a typical source of error in real-time PCR quantification of mitochondrial DNA content in human peripheral blood cells. Eur J Med Res 2004; 9: 371-377.
- Hurtado-Roca Y, Ledesma M, Gonzalez-Lazaro M, Moreno-Loshuertos R, Fernandez-Silva P, Enriquez JA, et al. Adjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts. PLoS One 2016; 11: 163770.
- Zhang P, Samuels DC, Wang J, Zhao S, Shyr Y, Guo Y. Mitochondria single nucleotide variation across six blood cell types. Mitochondrion 2016; 28: 16-22.
- Malik AN, Czajka A, Cunningham P. Accurate quantification of mouse mitochondrial DNA without co-amplification of nuclear mitochondrial insertion sequences. Mitochondrion 2016; 29: 59-64.
References
Giorgi C, Agnoletto C, Bononi A, Bonora M, De Marchi E, Marchi S, et al. Mitochondrial calcium homeostasis as potential target for mitochondrial medicine. Mitochondrion 2012; 12: 77-85.
Lopez-Armada MJ, Riveiro-Naveira RR, Vaamonde-Garcia C, Valcarcel-Ares MN. Mitochondrial dysfunction and the inflammatory response. Mitochondrion 2013; 13: 106-118.
Miller WL. Steroid hormone synthesis in mitochondria. Mol Cell Endocrinol 2013; 379: 62-73.
Patterson HC, Gerbeth C, Thiru P, Vögtle NF, Knoll M, Shahsafaei A, et al. A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling. Proc Natl Acad Sci U S A 2015; 112: 5679-5688.
Chandel NS. Evolution of Mitochondria as Signaling Organelles. Cell Metab 2015; 22: 204-206.
Chandel NS. Mitochondria as signaling organelles. BMC Biol 2014; 12: 34.
Wang C, Youle RJ. The role of mitochondria in apoptosis*. Annu Rev Genet 2009; 43: 95-118.
Chistiakov DA, Shkurat TP, Melnichenko AA, Grechko AV, Orekhov AN. The role of mitochondrial dysfunction in cardiovascular disease: a brief review. Ann Med 2018; 50: 121-127.
Ward MS, Fortheringham AK, Cooper ME, Forbes JM. Targeting advanced glycation endproducts and mitochondrial dysfunction in cardiovascular disease. Curr Opin Pharmacol 2013; 13: 654-661.
Ballinger SW. Mitochondrial dysfunction in cardiovascular disease. Free Radic Biol Med 2005; 38: 1278-1295.
Kokotas H, Petersen MB, Willems PJ. Mitochondrial deafness. Clin Genet 2007; 71: 379-391.
Leishangthem BD, Sharma A, Bhatnagar A. Role of altered mitochondria functions in the pathogenesis of systemic lupus erythematosus. Lupus 2016; 25: 272-281.
Smith EF, Shaw PJ, De Vos KJ. The role of mitochondria in amyotrophic lateral sclerosis. Neurosci Lett 2019; 710: 132933.
Duffy LM, Chapman AL, Shaw PJ, Grierson AJ. Review: The role of mitochondria in the pathogenesis of amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 2011; 37: 336-352.
Borthwick GM, Johnson MA, Ince PG, Shaw PJ, Turnbull DM. Mitochondrial enzyme activity in amyotrophic lateral sclerosis: implications for the role of mitochondria in neuronal cell death. Ann Neurol 1999; 46: 787-790.
Siddiqui MF, Elwell C, Johnson MH. Mitochondrial Dysfunction in Autism Spectrum Disorders. Autism Open Access 2016;6: 1000190.
Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 2012; 17: 290-314.
Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet 1993; 4: 289-294.
Meng F, He Z, Tang X, Zheng J, Jin X, Zhu Y, et al. Contribution of the tRNA(Ile) 4317A-->G mutation to the phenotypic manifestation of the deafness-associated mitochondrial 12S rRNA 1555A-->G mutation. J Biol Chem 2018; 293: 3321-3334.
McFarland R, Schaefer AM, Gardner JL, Lynn S, Hayes CM, Barron MJ, et al. Familial myopathy: new insights into the T14709C mitochondrial tRNA mutation. Ann Neurol 2004; 55: 478-484.
Hao H, Bonilla E, Manfredi G, DiMauro S, Moraes CT. Segregation patterns of a novel mutation in the mitochondrial tRNA glutamic acid gene associated with myopathy and diabetes mellitus. Am J Hum Genet 1995; 56: 1017-1025.
Chen N, Wen S, Sun X, Fang Q, Huang L, Liu S, et al. Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis. Sci Rep 2016; 6: 37404.
Tin A, Grams ME, Ashar FN, Lane JA, Rosenberg AZ, Grove ML, et al. Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study. J Am Soc Nephrol 2016; 27: 2467-2473.
Lee JY, Lee DC, Im JA, Lee JW. Mitochondrial DNA copy number in peripheral blood is independently associated with visceral fat accumulation in healthy young adults. Int J Endocrinol 2014; 2014: 586017.
Lee SH, Chung DJ, Lee HS, Kim TJ, Kim MH, Jeong HJ, et al. Mitochondrial DNA copy number in peripheral blood in polycystic ovary syndrome. Metabolism 2011; 60: 1677-1682.
Zhang J, Xu S, Xu Y, Liu Y, Li Z, Zhang Y, et al. Relation of Mitochondrial DNA Copy Number in Peripheral Blood to Postoperative Atrial Fibrillation After Isolated Off-Pump Coronary Artery Bypass Grafting. Am J Cardiol 2017; 119: 473-477.
Sun Y, Zhang L, Ho SS, Wu X, Gu J. Lower mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of endometrial cancer. Mol Carcinog 2016; 55: 1111-1117.
28. Tu H, Gu J, Meng QH, Kim J, Davis JW, He Y, et al. Mitochondrial DNA copy number in peripheral blood leukocytes and the aggressiveness of localized prostate cancer. Oncotarget 2015; 6: 41988-41996.
Shen J, Gopalakrishnan V, Lee JE, Fang S, Zhao H. Mitochondrial DNA copy number in peripheral blood and melanoma risk. PLoS One 2015; 10: 131649.
Melkonian SC, Wang X, Gu J, Matin SF, Tannir NM, Wood CG, et al. Mitochondrial DNA copy number in peripheral blood leukocytes and the risk of clear cell renal cell carcinoma. Carcinogenesis 2015; 36: 249-255.
Lemnrau A, Brook MN, Fletcher O, Coulson P, Tomczyk K, Jones M, et al. Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer. Cancer Res 2015; 75: 2844-2850.
Zhou W, Zhu M, Gui M, Huang L, Long Z, Wang L, et al. Peripheral blood mitochondrial DNA copy number is associated with prostate cancer risk and tumor burden. PLoS One 2014; 9: 109470.
Xu E, Sun W, Gu J, Chow WH, Ajani JA, Wu X. Association of mitochondrial DNA copy number in peripheral blood leukocytes with risk of esophageal adenocarcinoma. Carcinogenesis 2013; 34: 2521-2524.
Xie H, Lev D, Gong Y, Wang S, Pollock RE, Wu X, et al. Reduced mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of soft tissue sarcoma. Carcinogenesis 2013; 34: 1039-1043.
Purdue MP, Hofmann JN, Colt JS, Hoxha M, Ruterbusch JJ, Davis FG, et al. A case-control study of peripheral blood mitochondrial DNA copy number and risk of renal cell carcinoma. PLoS One 2012; 7: 43149.
Yoo HJ, Park M, Kim SA. Difference in mitochondrial DNA copy number in peripheral blood cells between probands with autism spectrum disorders and their unaffected siblings. World J Biol Psychiatry 2017; 18: 151-156.
Chen S, Li Z, He Y, Zhang F, Li H, Liao Y, et al. Elevated mitochondrial DNA copy number in peripheral blood cells is associated with childhood autism. BMC Psychiatry 2015; 15: 50.
He Y, Tang J, Li Z, Li H, Liao Y, Tang Y, et al. Leukocyte mitochondrial DNA copy number in blood is not associated with major depressive disorder in young adults. PLoS One 2014; 9: 96869.
Pyle A, Anugrha H, Kurzawa-Akanbi M, Yarnall A, Burn D, Hudson G. Reduced mitochondrial DNA copy number is a biomarker of Parkinson's disease. Neurobiol Aging 2016; 38: 216.
Sun J, Longchamps RJ, Piggott DA, Castellani CA, Sumpter JA, Brown TT, et al. Association Between HIV Infection and Mitochondrial DNA Copy Number in Peripheral Blood: A Population-Based, Prospective Cohort Study. J Infect Dis 2019; 219: 1285-1293.
Yang Y, Yang J, Yu B, Li L, Luo L, Wu F, et al. Association between circulating mononuclear cell mitochondrial DNA copy number and in-hospital mortality in septic patients: A prospective observational study based on the Sepsis-3 definition. PLoS One 2019; 14: 212808.
Lei L, Guo J, Shi X, Zhang G, Kang H, Sun C, et al. Mitochondrial DNA copy number in peripheral blood cell and hypertension risk among mining workers: a case-control study in Chinese coal miners. J Hum Hypertens 2017; 31: 585-590.
Mengel-From J, Thinggaard M, Dalgard C, Kyvik KO, Christensen K, Christiansen L. Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly. Hum Genet 2014; 133: 1149-1159.
Ashar FN, Zhang Y, Longchamps RJ, Lane J, Moes A, Grove ML, et al. Association of Mitochondrial DNA Copy Number With Cardiovascular Disease. JAMA Cardiol 2017; 2: 1247-1255.
Abo T, Kawate T, Itoh K, Kumagai K. Studies on the bioperiodicity of the immune response. I. Circadian rhythms of human T, B, and K cell traffic in the peripheral blood. J Immunol 1981; 126: 1360-1363.
Miyawaki T, Taga K, Nagaoki T, Seki H, Suzuki Y, Taniguchi N. Circadian changes of T lymphocyte subsets in human peripheral blood. Clin Exp Immunol 1984; 55: 618-622.
Shuster RC, Rubenstein AJ, Wallace DC. Mitochondrial DNA in anucleate human blood cells. Biochem Biophys Res Commun 1988; 155: 1360-1365.
Nemzek JA, Bolgos GL, Williams BA, Remick DG. Differences in normal values for murine white blood cell counts and other hematological parameters based on sampling site. Inflamm Res 2001; 50: 523-527.
Bain BJ. Ethnic and sex differences in the total and differential white cell count and platelet count. J Clin Pathol 1996; 49: 664-666.
Boudreau LH, Duchez AC, Cloutier N, Soulet D, Martin N, Bollinger J, et al. Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation. Blood 2014; 124: 2173-2183.
Urata M, Koga-Wada Y, Kayamori Y, Kang D. Platelet contamination causes large variation as well as overestimation of mitochondrial DNA content of peripheral blood mononuclear cells. Ann Clin Biochem 2008; 45: 513-514.
Banas B, Kost BP, Goebel FD. Platelets, a typical source of error in real-time PCR quantification of mitochondrial DNA content in human peripheral blood cells. Eur J Med Res 2004; 9: 371-377.
Hurtado-Roca Y, Ledesma M, Gonzalez-Lazaro M, Moreno-Loshuertos R, Fernandez-Silva P, Enriquez JA, et al. Adjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts. PLoS One 2016; 11: 163770.
Zhang P, Samuels DC, Wang J, Zhao S, Shyr Y, Guo Y. Mitochondria single nucleotide variation across six blood cell types. Mitochondrion 2016; 28: 16-22.
Malik AN, Czajka A, Cunningham P. Accurate quantification of mouse mitochondrial DNA without co-amplification of nuclear mitochondrial insertion sequences. Mitochondrion 2016; 29: 59-64.