Evidence for multi-copy Mega-NUMTs in the human genome.

Autor:	Lutz-Bonengel S; Institute of Forensic Medicine, Medical Center, University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany., Niederstätter H; Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria., Naue J; Institute of Forensic Medicine, Medical Center, University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany., Koziel R; Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck 6020, Austria., Yang F; Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK., Sänger T; Institute of Forensic Medicine, Medical Center, University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany., Huber G; Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria., Berger C; Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria., Pflugradt R; State Investigation Department of Lower Saxony, Hannover 30169, Germany., Strobl C; Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria., Xavier C; Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria., Volleth M; Magdeburg University Hospital, Institute of Human Genetics, Otto von Guericke University, Magdeburg 39120, Germany., Weiß SC; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Freiburg 79104, Germany., Irwin JA; DNA Support Unit, FBI Laboratory, Quantico, VA 22135, USA., Romsos EL; U.S. National Institute of Standards and Technology, Biomolecular Measurement Division, Gaithersburg, MD 20899, USA., Vallone PM; U.S. National Institute of Standards and Technology, Biomolecular Measurement Division, Gaithersburg, MD 20899, USA., Ratzinger G; Department of Dermatology, Venereology and Allergy, Medical University of Innsbruck, Innsbruck 6020, Austria., Schmuth M; Department of Dermatology, Venereology and Allergy, Medical University of Innsbruck, Innsbruck 6020, Austria., Jansen-Dürr P; Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck 6020, Austria., Liehr T; Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Jena 07747, Germany., Lichter P; German Cancer Research Center, Molecular Genetics, Heidelberg 69120, Germany., Parsons TJ; International Commission on Missing Persons, The Hague 2514 AA, Netherlands.; Forensic Science Program, The Pennsylvania State University, University Park, PA 16802, USA., Pollak S; Institute of Forensic Medicine, Medical Center, University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany., Parson W; Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria.; Forensic Science Program, The Pennsylvania State University, University Park, PA 16802, USA.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2021 Feb 22; Vol. 49 (3), pp. 1517-1531.
DOI:	10.1093/nar/gkaa1271
Abstrakt:	The maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals. Cells without nuclear DNA, i.e. thrombocytes and hair shafts, only showed the mitotype of haplogroup (hg) V. Skin biopsies were prepared to generate ρ° cells void of mtDNA, sequencing of which resulted in a hg U4c1 mitotype. The position of the Mega-NUMT sequence was determined by fluorescence in situ hybridization and two different quantitative PCR assays were used to determine the number of contributing mtDNA copies. Thus, evidence for the presence of repetitive, full mitogenome Mega-NUMTs matching haplogroup U4c1 in various tissues of eight maternally related individuals was provided. Multi-copy Mega-NUMTs mimic mixtures of mtDNA that cannot be experimentally avoided and thus may appear in diverse fields of mtDNA research and diagnostics. We demonstrate that hair shaft mtDNA sequencing provides a simple but reliable approach to exclude NUMTs as source of misleading results. (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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