No Evidence of Persistence or Inheritance of Mitochondrial DNA Copy Number in Holocaust Survivors and Their Descendants
Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic-ecollection
Typ dokumentu časopisecké články
PubMed
32211017
PubMed Central
PMC7069217
DOI
10.3389/fgene.2020.00087
Knihovny.cz E-zdroje
- Klíčová slova
- Holocaust-psychic trauma, copy number variation, mitochondrial DNA, posttraumatic stress disorder, quantitative PCR,
- Publikační typ
- časopisecké články MeSH
Mitochondrial DNA copy number has been previously shown to be elevated with severe and chronic stress, as well as stress-related pathology like Major Depressive Disorder (MDD) and post-traumatic stress disorder (PTSD). While experimental data point to likely recovery of mtDNA copy number changes after the stressful event, time needed for full recovery and whether it can be achieved are still unknown. Further, while it has been shown that stress-related mtDNA elevation affects multiple tissues, its specific consequences for oogenesis and maternal inheritance of mtDNA has never been explored. In this study, we used qPCR to quantify mtDNA copy number in 15 Holocaust survivors and 102 of their second- and third-generation descendants from the Czech Republic, many of whom suffer from PTSD, and compared them to controls in the respective generations. We found no significant difference in mtDNA copy number in the Holocaust survivors compared to controls, whether they have PTSD or not, and no significant elevation in descendants of female Holocaust survivors as compared to descendants of male survivors or controls. Our results showed no evidence of persistence or inheritance of mtDNA changes in Holocaust survivors, though that does not rule out effects in other tissues or mitigating mechanism for such changes.
1st Neurology Department Hospital St Anne and School of Medicine Masaryk University Brno Czechia
European Bioinformatics Institute Wellcome Genome Campus Hinxton United Kingdom
Mendel Centre for Plant Genomics and Proteomics CEITEC Masaryk University Brno Czechia
National Centre for Biomolecular Research Faculty of Science Masaryk University Brno Czechia
Neuroscience Centre CEITEC Masaryk University Brno Czechia
Wellcome Sanger Institute Wellcome Genome Campus Hinxton United Kingdom
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Barritt J. A., Kokot M., Cohen J., Steuerwald N., Brenner C. A. (2002). Quantification of human ooplasmic mitochondria. Reprod. Biomed. Online 4, 243–247. 10.1016/S1472-6483(10)61813-5 PubMed DOI
Bersani F. S., Morley C., Lindqvist D., Epel E. S., Picard M., Yehuda R., et al. (2016). Mitochondrial DNA copy number is reduced in male combat veterans with PTSD. Prog. Neuropsychopharmacol. Biol. Psychiatry 64, 10–17. 10.1016/j.pnpbp.2015.06.012 PubMed DOI
Brunst K. J., Guerra M. S., Gennings C., Hacker M., Jara C., Enlow M. B., et al. (2017). Maternal lifetime stress and prenatal psychological functioning and decreased placental mitochondrial DNA copy number in the PRISM study. Am. J. Epidemiol. 186, 1227–1236. 10.1093/aje/kwx183 PubMed DOI PMC
Cai N., Chang S., Li Y., Li Q., Hu J., Liang J., et al. (2015. b). Genetic control over mtDNA and its relationship to major depressive disorder. Curr. Biol. 25, 3170–3177. 10.1016/j.cub.2015.10.065 PubMed DOI PMC
Cai N., Li Y., Chang S., Liang J., Lin C., Zhang X., et al. (2015. a). Molecular signatures of major depression. Curr. Biol. 25, 1146–1156. 10.1016/j.cub.2015.03.008 PubMed DOI PMC
Carew J. S., Nawrocki S. T., Xu R. H., Dunner K., McConkey D. J., Wierda W. G., et al. (2004). Increased mitochondrial biogenesis in primary leukemia cells: the role of endogenous nitric oxide and impact on sensitivity to fludarabine. Leukemia 18, 1934–1940. 10.1038/sj.leu.2403545 PubMed DOI
Consortium T., 1000 G. P. and The 1000 Genomes Project Consortium (2015). A global reference for human genetic variation. Nature 526, 68–74. 10.1038/nature15393 PubMed DOI PMC
Cotterill M., Harris S. E., Fernandez E. C., Lu J., Huntriss J. D., Campbell B. K., et al. (2013). The activity and copy number of mitochondrial DNA in ovine oocytes throughout oogenesis in vivo and during oocyte maturation in vitro . Mol. Hum. Reprod. 19, 444–450. 10.1093/molehr/gat013 PubMed DOI PMC
Cree L. M., Samuels D. C., de Sousa Lopes S. C., Rajasimha H. K., Wonnapinij P., Mann J. R., et al. (2008). A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat. Genet. 40, 249–254. 10.1038/ng.2007.63 PubMed DOI
Czarny P., Wigner P., Strycharz J., Swiderska E., Synowiec E., Szatkowska M., et al. (2019). Mitochondrial DNA copy number, damage, repair and degradation in depressive disorder. World J. Biol. Psychiatry 13, 1–11. 10.1080/15622975.2019.1588993 PubMed DOI
DePristo M. A., Banks E., Poplin R., Garimella K. V., Maguire J. R., Hartl C., et al. (2011). A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491–498. 10.1038/ng.806 PubMed DOI PMC
Edwards A. C., Aggen S. H., Cai N., Bigdeli T. B., Peterson R. E., Docherty A. R., et al. (2016). Chronicity of depression and molecular markers in a large sample of han Chinese women. Depression Anxiety 33, 1048–1054. 10.1002/da.22517 PubMed DOI PMC
Falkenberg M., Larsson N.-G., Gustafsson C. M. (2007). DNA Replication and Transcription in Mammalian Mitochondria. Annu. Rev. Biochem. 76, 679–699. 10.1146/annurev.biochem.76.060305.152028 PubMed DOI
Giles R. E., Blanc H., Cann H. M., Wallace D. C. (1980). Maternal inheritance of human mitochondrial DNA. Proc. Natl. Acad. Sci. U. S. A. 77, 6715–6719. 10.1073/pnas.77.11.6715 PubMed DOI PMC
Holsboer F. (2000). The Corticosteroid Receptor Hypothesis of Depression. Neuropsychopharmacology 23, 477–501. 10.1016/S0893-133X(00)00159-7 PubMed DOI
Hurtado-Roca Y., Ledesma M., Gonzalez-Lazaro M., Moreno-Loshuertos R., Fernandez-Silva P., Enriquez J. A., et al. (2016). Adjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts. PLoS One 11, e0163770. 10.1371/journal.pone.0163770 PubMed DOI PMC
Jenuth J. P., Peterson A. C., Fu K., Shoubridge E. A. (1996). Random genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNA. Nat. Genet. 14, 146–151. 10.1038/ng1096-146 PubMed DOI
Kageyama Y., Kasahara T., Kato M., Sakai S., Deguchi Y., Tani M., et al. (2018). The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression. J. Affect. Disord. 233, 15–20. 10.1016/j.jad.2017.06.001 PubMed DOI
Kelly R., Mahmud A., McKenzie M., Trounce I., St John J. (2012). Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear-encoded DNA polymerase gamma A. Nucleic Acids Res. 40, 10124–10138. 10.1093/nar/gks770 PubMed DOI PMC
Kloet E. R., de Kloet E. R., Joëls M., Holsboer F. (2005). Stress and the brain: from adaptation to disease. Nat. Rev. Neurosci. 6, 463–475. 10.1038/nrn1683 PubMed DOI
Konečná K., Lyčka M., Nohelová L., Petráková M., Fňašková M., Koriťáková E., et al. (2019). Holocaust history is not reflected in telomere homeostasis in survivors and their offspring. J. Psychiatr. Res. 117, 7–14. 10.1016/j.jpsychires.2019.06.018 PubMed DOI
Kukat C., Davies K. M., Wurm C. A., Spåhr H., Bonekamp N. A., Kühl I., et al. (2015). Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid. Proc. Natl. Acad. Sci. U. S. A. 112, 11288–11293. 10.1073/pnas.1512131112 PubMed DOI PMC
Lan Q., Lim U., Liu C.-S., Weinstein S. J., Chanock S., Bonner M. R., et al. (2008). A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma. Blood 112, 4247–4249. 10.1182/blood-2008-05-157974 PubMed DOI PMC
Li H., Handsaker B., Wysoker A., Fennell T., Ruan J., Homer N., et al. (2009). The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079. 10.1093/bioinformatics/btp352 PubMed DOI PMC
Lindqvist D., Wolkowitz O. M., Picard M., Ohlsson L., Bersani F. S., Fernström J., et al. (2018). Circulating cell-free mitochondrial DNA, but not leukocyte mitochondrial DNA copy number, is elevated in major depressive disorder. Neuropsychopharmacology 43, 1557–1564. 10.1038/s41386-017-0001-9 PubMed DOI PMC
Malik A., Shahni R., Iqbal M. (2009). Increased peripheral blood mitochondrial DNA in type 2 diabetic patients with nephropathy. Diabetes Res. Clin. Pract. 86, e22–e24. 10.1016/j.diabres.2009.07.002 PubMed DOI
Manoli I., Alesci S., Blackman M. R., Su Y. A., Rennert O. M., Chrousos G. P. (2007). Mitochondria as key components of the stress response. Trends Endocrinol. Metab. 18, 190–198. 10.1016/j.tem.2007.04.004 PubMed DOI
McKenna A., Hanna M., Banks E., Sivachenko A., Cibulskis K., Kernytsky A., et al. (2010). The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303. 10.1101/gr.107524.110 PubMed DOI PMC
Mengel-From J., Thinggaard M., Dalgård C., Kyvik K. O., Christensen K., Christiansen L. (2014). Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly. Hum. Genet. 133, 1149–1159. 10.1007/s00439-014-1458-9 PubMed DOI PMC
Otsuka I., Izumi T., Boku S., Kimura A., Zhang Y., Mouri K., et al. (2017). Aberrant telomere length and mitochondrial DNA copy number in suicide completers. Sci. Rep. 7, 3176. 10.1038/s41598-017-03599-8 PubMed DOI PMC
Reynier P., May-Panloup P., Chrétien M. F., Morgan C. J., Jean M., Savagner F., et al. (2001). Mitochondrial DNA content affects the fertilizability of human oocytes. Mol. Hum. Reprod. 7, 425–429. 10.1093/molehr/7.5.425 PubMed DOI
Ridout K. K., Parade S. H., Marsit C. J., Carpenter L. L., Price L. H., Philip N. S., et al. (2019). Neuroendocrine function and mitochondrial DNA copy number alterations with early stress and psychopathology. Psychoneuroendocrinology 100, S51. 10.1016/j.psyneuen.2018.12.175 DOI
Robin E. D., Wong R. (1988). Mitochondrial DNA molecules and virtual number of mitochondria per cell in mammalian cells. J. Cell. Physiol. 136, 507–513. 10.1002/jcp.1041360316 PubMed DOI
Sagi-Schwartz A., Bakermans-Kranenburg M., Linn S., van IJzendoorn M. (2013). Against All Odds: Genocidal Trauma Is Associated with Longer Life-Expectancy of the Survivors. PLoS One 8, e69179. 10.1371/journal.pone.0069179 PubMed DOI PMC
Santos T., Shourbagy S., St John J. (2006). Mitochondrial content reflects oocyte variability and fertilization outcome. Fertil. Steril. 85, 584–591. 10.1016/j.fertnstert.2005.09.017 PubMed DOI
Scarpulla R. C., Vega R. B., Kelly D. P. (2012). Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol. Metab. 23, 459–466. 10.1016/j.tem.2012.06.006 PubMed DOI PMC
Scarpulla R. C. (2008). Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-1-related coactivator. Ann. N. Y. Acad. Sci. 1147, 321–334. 10.1196/annals.1427.006 PubMed DOI PMC
Simoni L., Calafell F., Pettener D., Bertranpetit J., Barbujani G. (2000). Geographic patterns of mtDNA Diversity in Europe. Am. J. Hum. Genet. 66, 262–278. 10.1086/302706 PubMed DOI PMC
Speed D., Cai N., UCLEB Consortium. Johnson M. R., Nejentsev S., Balding D. (2017). Reevaluation of SNP heritability in complex human traits. Nat. Genet. 49, 986–992. 10.1038/ng.3865 PubMed DOI PMC
St-Pierre J., Drori S., Uldry M., Silvaggi J. M., Rhee J., Jäger S., et al. (2006). Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127, 397–408. 10.1016/j.cell.2006.09.024 PubMed DOI
Su Y. A., Wu J., Zhang L., Zhang Q., Su D. M., He P., et al. (2008). Dysregulated mitochondrial genes and networks with drug targets in postmortem brain of patients with posttraumatic stress disorder (PTSD) revealed by human mitochondria-focused cDNA microarrays. Int. J. Biol. Sci. 4, 223–235. 10.7150/ijbs.4.223 PubMed DOI PMC
Torroni A., Richards M., Macaulay V., Forster P., Villems R., Nørby S., et al. (2000). mtDNA haplogroups and frequency patterns in Europe. Am. J. Hum. Genet. 66, 1173–1177. 10.1086/302789 PubMed DOI PMC
Tsujii N., Otsuka I., Okazaki S., Yanagi M., Numata S., Yamaki N., et al. (2019). Mitochondrial DNA copy number raises the potential of left frontopolar hemodynamic response as a diagnostic marker for distinguishing bipolar disorder from major depressive disorder. Front. Psychiatry 10, 312. 10.3389/fpsyt.2019.00312 PubMed DOI PMC
Tymofiyeva O., Blom E. H., Ho T. C., Connolly C. G., Lindqvist D., Wolkowitz O. M., et al. (2018). High levels of mitochondrial DNA are associated with adolescent brain structural hypoconnectivity and increased anxiety but not depression. J. Affect. Disord. 232, 283–290. 10.1016/j.jad.2018.02.024 PubMed DOI PMC
Tyrka A. R., Parade S. H., Price L. H., Kao H.-T., Porton B., Philip N. S., et al. (2016). Alterations of mitochondrial DNA copy number and telomere length with early adversity and psychopathology. Biol. Psychiatry 79, 78–86. 10.1016/j.biopsych.2014.12.025 PubMed DOI PMC
Verhoeven J. E., Révész D., Picard M., Epel E. E., Wolkowitz O. M., Matthews K. A., et al. (2018). Depression, telomeres and mitochondrial DNA: between- and within-person associations from a 10-year longitudinal study. Mol. Psychiatry 23, 850–857. 10.1038/mp.2017.48 PubMed DOI
Wai T., Teoli D., Shoubridge E. A. (2008). The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes. Nat. Genet. 40, 1484–1488. 10.1038/ng.258 PubMed DOI
Wang D., Li Z., Liu W., Zhou J., Ma X., Tang J., et al. (2018). Differential mitochondrial DNA copy number in three mood states of bipolar disorder. BMC Psychiatry 18, 149. 10.1186/s12888-018-1717-8 PubMed DOI PMC
Weissensteiner H., Pacher D., Kloss-Brandstätter A., Forer L., Specht G., Bandelt H.-J., et al. (2016). HaploGrep 2: mitochondrial haplogroup classification in the era of high-throughput sequencing. Nucleic Acids Res. 44, W58–W63. 10.1093/nar/gkw233 PubMed DOI PMC
Yehuda R., Schmeidler J., Wainberg M., Binder-Brynes K., Duvdevani T. (1998). Vulnerability to posttraumatic stress disorder in adult offspring of Holocaust survivors. Am. J. Psychiatry 155, 1163–1171. 10.1176/ajp.155.9.1163 PubMed DOI
Zhang L., Zhou R., Li X., Ursano R., Li H. (2006). Stress-induced change of mitochondria membrane potential regulated by genomic and non-genomic GR signaling: a possible mechanism for hippocampus atrophy in PTSD. Med. Hypotheses 66, 1205–1208. 10.1016/j.mehy.2005.11.041 PubMed DOI
Zuiden M. v., Geuze E., Willemen H. L. D. M., Vermetten E., Maas M., Amarouchi K., et al. (2012). Glucocorticoid receptor pathway components predict posttraumatic stress disorder symptom development: a prospective study. Biol. Psychiatry 71, 309–316. 10.1016/j.biopsych.2011.10.026 PubMed DOI
Lifelong impact of extreme stress on the human brain: Holocaust survivors study