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Extraordinary claims require extraordinary evidence in asserted mtDNA biparental inheritance.
Forensic Sci Int Genet. 2020 Jul; 47:102274.FS

Abstract

A breakthrough article published in PNAS by Luo et al. challenges a central dogma in biology which states that the mitochondrial DNA (mtDNA) in humans is inherited exclusively from the mother. We re-analyzed original FASTQ files and results reported by Luo et al. to investigate methodological issues (e.g. nuclear mitochondrial DNA or NUMTs, DNA rearrangements) that could lead to biological misinterpretations. A comprehensive analysis of their data reveals several methodological and analytical issues that must be carefully addressed before challenging the current paradigm. We first show that the probability of the findings described by the authors is extremely small (most likely below 10-37). The sequencing replicates from the same donors show aberrations in the variants detected that need further investigation to exclude contributions from other sources or methodological artifacts. Applying the principle of reductio ad absurdum, we demonstrate that the nuclear factor invoked by the authors to explain the phenomenon would need to be extraordinarily complex and precise to preclude linear accumulation of mtDNA lineages across generations, which would make the appearance of mixed haplotypes a much more frequent event in the population. We discuss alternate scenarios that explain findings of the same nature as reported by Luo et al., in the context of in-vitro fertilization and therapeutic mtDNA replacement ooplasmic transplantation.

Authors+Show Affiliations

Unidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia, Spain. Electronic address: antonio.salas@usc.es.Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, 6020, Austria.Department of Mathematics, University of Hamburg, Hamburg, 20146, Germany.Unidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia, Spain.Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, 6020, Austria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32330850

Citation

Salas, Antonio, et al. "Extraordinary Claims Require Extraordinary Evidence in Asserted mtDNA Biparental Inheritance." Forensic Science International. Genetics, vol. 47, 2020, p. 102274.
Salas A, Schönherr S, Bandelt HJ, et al. Extraordinary claims require extraordinary evidence in asserted mtDNA biparental inheritance. Forensic Sci Int Genet. 2020;47:102274.
Salas, A., Schönherr, S., Bandelt, H. J., Gómez-Carballa, A., & Weissensteiner, H. (2020). Extraordinary claims require extraordinary evidence in asserted mtDNA biparental inheritance. Forensic Science International. Genetics, 47, 102274. https://doi.org/10.1016/j.fsigen.2020.102274
Salas A, et al. Extraordinary Claims Require Extraordinary Evidence in Asserted mtDNA Biparental Inheritance. Forensic Sci Int Genet. 2020;47:102274. PubMed PMID: 32330850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extraordinary claims require extraordinary evidence in asserted mtDNA biparental inheritance. AU - Salas,Antonio, AU - Schönherr,Sebastian, AU - Bandelt,Hans-Jürgen, AU - Gómez-Carballa,Alberto, AU - Weissensteiner,Hansi, Y1 - 2020/03/12/ PY - 2019/12/19/received PY - 2020/03/08/revised PY - 2020/03/11/accepted PY - 2020/4/25/pubmed PY - 2020/4/25/medline PY - 2020/4/25/entrez KW - Biparental mtDNA inheritance KW - In-vitro fertilization KW - Mixtures KW - Next-generation sequencing KW - Paternal transmission KW - Therapeutic mtDNA replacement ooplasmic transplantation SP - 102274 EP - 102274 JF - Forensic science international. Genetics JO - Forensic Sci Int Genet VL - 47 N2 - A breakthrough article published in PNAS by Luo et al. challenges a central dogma in biology which states that the mitochondrial DNA (mtDNA) in humans is inherited exclusively from the mother. We re-analyzed original FASTQ files and results reported by Luo et al. to investigate methodological issues (e.g. nuclear mitochondrial DNA or NUMTs, DNA rearrangements) that could lead to biological misinterpretations. A comprehensive analysis of their data reveals several methodological and analytical issues that must be carefully addressed before challenging the current paradigm. We first show that the probability of the findings described by the authors is extremely small (most likely below 10-37). The sequencing replicates from the same donors show aberrations in the variants detected that need further investigation to exclude contributions from other sources or methodological artifacts. Applying the principle of reductio ad absurdum, we demonstrate that the nuclear factor invoked by the authors to explain the phenomenon would need to be extraordinarily complex and precise to preclude linear accumulation of mtDNA lineages across generations, which would make the appearance of mixed haplotypes a much more frequent event in the population. We discuss alternate scenarios that explain findings of the same nature as reported by Luo et al., in the context of in-vitro fertilization and therapeutic mtDNA replacement ooplasmic transplantation. SN - 1878-0326 UR - https://www.unboundmedicine.com/medline/citation/32330850/Extraordinary_claims_require_extraordinary_evidence_in_asserted_mtDNA_biparental_inheritance L2 - https://linkinghub.elsevier.com/retrieve/pii/S1872-4973(20)30045-4 DB - PRIME DP - Unbound Medicine ER -
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