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

Cell Nucleus / genetics DNA Copy Number Variations DNA, Mitochondrial Female Genome, Human Humans Male Pedigree Sequence Analysis, DNA

Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
22 02 2021
Historique:
accepted: 22 12 2020
revised: 11 12 2020
received: 04 08 2020
pubmed: 16 1 2021
medline: 4 3 2021
entrez: 15 1 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1093/nar/gkaa1271 PMID: 33450006 PMC: PMC7897518
pubmed: 33450006
pii: 6101596
doi: 10.1093/nar/gkaa1271
pmc: PMC7897518
doi:

Substances chimiques

DNA, Mitochondrial 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1517-1531

Subventions

Organisme : Wellcome Trust
ID : WT098051
Pays : United Kingdom

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Sabine Lutz-Bonengel (S)

Institute of Forensic Medicine, Medical Center, University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany.

Harald Niederstätter (H)

Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria.

Jana Naue (J)

Institute of Forensic Medicine, Medical Center, University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany.

Rafal Koziel (R)

Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck 6020, Austria.

Fengtang Yang (F)

Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

Timo Sänger (T)

Institute of Forensic Medicine, Medical Center, University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany.

Gabriela Huber (G)

Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria.

Cordula Berger (C)

Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria.

René Pflugradt (R)

State Investigation Department of Lower Saxony, Hannover 30169, Germany.

Christina Strobl (C)

Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria.

Catarina Xavier (C)

Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck 6020, Austria.

Marianne Volleth (M)

Magdeburg University Hospital, Institute of Human Genetics, Otto von Guericke University, Magdeburg 39120, Germany.

Sandra Carina Weiß (SC)

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Freiburg 79104, Germany.

Jodi A Irwin (JA)

DNA Support Unit, FBI Laboratory, Quantico, VA 22135, USA.

Erica L Romsos (EL)

U.S. National Institute of Standards and Technology, Biomolecular Measurement Division, Gaithersburg, MD 20899, USA.

Peter M Vallone (PM)

U.S. National Institute of Standards and Technology, Biomolecular Measurement Division, Gaithersburg, MD 20899, USA.

Gudrun Ratzinger (G)

Department of Dermatology, Venereology and Allergy, Medical University of Innsbruck, Innsbruck 6020, Austria.

Matthias Schmuth (M)

Department of Dermatology, Venereology and Allergy, Medical University of Innsbruck, Innsbruck 6020, Austria.

Pidder Jansen-Dürr (P)

Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck 6020, Austria.

Thomas Liehr (T)

Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Jena 07747, Germany.

Peter Lichter (P)

German Cancer Research Center, Molecular Genetics, Heidelberg 69120, Germany.

Thomas J Parsons (TJ)

International Commission on Missing Persons, The Hague 2514 AA, Netherlands.
Forensic Science Program, The Pennsylvania State University, University Park, PA 16802, USA.

Stefan Pollak (S)

Institute of Forensic Medicine, Medical Center, University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany.

Walther 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.

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Classifications MeSH

questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Noyau de la cellule › Evidence for multi-copy Mega-NUMTs in the human genome.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Evidence for multi-copy Mega-NUMTs in the human genome.
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN mitochondrial › Evidence for multi-copy Mega-NUMTs in the human genome.
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome humain › Evidence for multi-copy Mega-NUMTs in the human genome.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Evidence for multi-copy Mega-NUMTs in the human genome.
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Pedigree › Evidence for multi-copy Mega-NUMTs in the human genome.
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Evidence for multi-copy Mega-NUMTs in the human genome.