title: Quantitative assessment of heteroplasmy of mitochondrial genome: perspectives in diagnostics and methodological pitfalls.
abstract: The role of alterations of mitochondrial DNA (mtDNA) in the development of human pathologies is not understood well. Most of mitochondrial mutations are characterized by the phenomenon of heteroplasmy which is defined as the presence of a mixture of more than one type of an organellar genome within a cell or tissue. The level of heteroplasmy varies in wide range, and the expression of disease is dependent on the percent of alleles bearing mutations, thus allowing consumption that an upper threshold level may exist beyond which the mitochondrial function collapses. Recent findings have demonstrated that some mtDNA heteroplasmic mutations are associated with widely spread chronic diseases, including atherosclerosis and cancer. Actually, each etiological mtDNA mutation has its own heteroplasmy threshold that needs to be measured. Therefore, quantitative evaluation of a mutant allele of mitochondrial genome is an obvious methodological challenge, since it may be a keystone for diagnostics of individual genetic predisposition to the disease. This review provides a comprehensive comparison of methods applicable to the measurement of heteroplasmy level of mitochondrial mutations associated with the development of pathology, in particular, in atherosclerosis and its clinical manifestations.
authors.affiliation: Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow 121552, Russia ; Laboratory of Cellular Mechanisms of Atherogenesis, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Sobenin
authors.affiliation: Laboratory of Cellular Mechanisms of Atherogenesis, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia.
authors.forename: Konstantin Y
authors.initials: KY
authors.lastname: Mitrofanov
authors.affiliation: Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow 121552, Russia ; Laboratory of Cellular Mechanisms of Atherogenesis, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Zhelankin
authors.affiliation: Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow 121552, Russia ; Laboratory of Cellular Mechanisms of Atherogenesis, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia.
authors.forename: Margarita A
authors.initials: MA
authors.lastname: Sazonova
authors.affiliation: Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow 121552, Russia.
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Postnov
authors.affiliation: Biological Faculty, N.P. Ogaryov Mordovian State University, Republic of Mordovia, Saransk 430005, Russia.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Revin
authors.affiliation: Biological Faculty, N.P. Ogaryov Mordovian State University, Republic of Mordovia, Saransk 430005, Russia ; Faculty of Medicine, School of Medical Sciences, University of New South Wales, Kensington, Sydney, NSW 2052, Australia ; School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
authors.affiliation: Laboratory of Cellular Mechanisms of Atherogenesis, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia ; Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow 143025, Russia.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Orekhov
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis / Q000379:methods*; D004272:DNA, Mitochondrial / Q000235:genetics*; D054629:Genome, Mitochondrial / Q000235:genetics*; D006801:Humans; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial