Mitochondrial DNA variants in early development and ART

Joke Mertens Filippo Zambelli
Persbericht

Gevarieerder mitochondriaal genoom bij ICSI kinderen

Mitochondria, de energiehuisjes die onze cellen doen ademen. Deze kleine celorganellen hebben hun eigen DNA, ook mtDNA genoemd. Het is ontzettend klein en komt voor in meerdere kopieën per cel. In tegenstelling tot het kern DNA dat je van je beide ouders meekrijgt, wordt het mtDNA enkel door je moeder meegegeven. Het zit in grote hoeveelheden in de eicel voor die bevrucht wordt. Tijdens de ontwikkeling van eicellen verdubbelt het mtDNA talloze keren, dit geeft een hoger risico op het ontstaan van varianten in het mitochondriaal genoom. Varianten zijn DNA-bouwstenen die verschillen van het referentiegenoom. In het kern DNA worden zulke varianten hersteld naar hun oorspronkelijke bouwstenen doordat er een herstelmechanisme aanwezig is. Dit ontbreekt echter voor het mtDNA. Uit onderzoek is gebleken dat de kans op zulke varianten nog hoger wordt als de eicellen tijdens hun ontwikkeling gestimuleerd worden met hormonen, zoals dit gebeurt in IVF en ICSI. IVF, of in vitro fertilisatie (voor vrouwelijke onvruchtbaarheid), en ICSI, of intracytoplasmatische sperma-injectie (voor mannelijke onvruchtbaarheid), zijn technieken die gebruikt worden om koppels die minder vruchtbaar zijn toch de kans te geven om hun kinderwens waar te maken.

Omdat mtDNA in meerdere kopieën per cel voorkomt, kan het ook zijn dat deze kopieën verschillen van elkaar. Wanneer een variant voorkomt in 100% van alle kopieën in de cel, dan is deze variant een homoplasmie. Wanneer een variant echter slechts in enkele kopieën voorkomt, wordt deze variant een heteroplasmie genoemd (zie figuur). Over het algemeen zijn deze homo- en heteroplasmieën goedaardig, maar in bepaalde gevallen kan een variant nadelige gevolgen hebben voor de cel en het organisme.

Maar hoe zit het dan met het mtDNA in kinderen die geboren zijn na IVF en ICSI? Deze kinderen hebben een lager geboortegewicht en een hoger risico op het ontwikkelen van bepaalde aandoeningen. Wat dit veroorzaakt is nog niet geweten, maar mtDNA is wel gelinkt met deze aandoeningen. Daarom vonden onderzoekers aan de Vrije Universiteit Brussel het uiterst interessant om het mtDNA in deze kinderen te onderzoeken op de aanwezigheid van varianten. Ze hebben dit onderzocht door bloedstalen te analyseren van 57 jongvolwassenen die geboren zijn na ICSI en die te vergelijken met 62 jongvolwassen die op natuurlijke wijze verwekt werden. Ook werden de homoplasmieën onderzocht buiten de haplogroep. Haplogroepen bestaan uit een aantal homoplasmieën die tot stand zijn gekomen doorheen de evolutie. Deze haplogroepen zorgden er bijvoorbeeld voor dat mensen uit Afrika efficiënter zuurstof kunnen omzetten in energie zonder al te veel warmte te verliezen, terwijl dit niet het geval is voor bijvoorbeeld mensen uit Noord-Europa, die meer warmte nodig hebben zodat ze kunnen overleven in koudere omgevingen. Je haplogroep beschrijft dus van waar in de wereld je voorouders afkomstig waren. Nu, de homoplasmieën die niet tot je haplogroep behoren zijn vaak ook interessant om te onderzoeken aangezien die pas in de recentere generaties te zien zijn en eigen zijn aan je familie. De onderzoekers vonden dat kinderen geboren na ICSI meer van deze homoplasmieën vertonen die nog niet beschreven zijn in de vakliteratuur. Deze varianten zijn niet per se gevaarlijk maar zijn wel interessant om bijvoorbeeld een mini-evolutie te onderzoeken of om te zien of sommige van deze varianten betrokken zijn bij bepaalde ziektebeelden. Ook de heteroplasmieën werden onderzocht. Deze varianten kunnen dus in een bepaald percentage voorkomen in de cel. Heteroplasmieën zijn moeilijker te analyseren aangezien het niet geweten is hoe belangrijk hun rol is in de cel. De onderzoekers hebben dit opgelost door de verschillende varianten met hun percentages bij elkaar op te tellen. Een voorbeeldje: een cel heeft drie varianten met een voorkomen van 10%, 50% en 90%, dan heeft deze cel een cumulatieve waarde van 150% (dit heet de cumulatieve frequentie) waarin de variant die in 90% voorkomt in de kopieën meer invloed heeft op het metabolisme dan de variant die slechts voorkomt in 10% van de kopieën. Op deze manier zagen de onderzoekers dat er meer kinderen zijn geboren na ICSI met een hogere cumulatieve frequentie dan kinderen die op een natuurlijke manier verwekt werden en dit in de regio’s van het mtDNA die verantwoordelijk zijn voor de aanmaak van eiwitten. Deze eiwitten zorgen voor de omzetting van zuurstof in energie. Kinderen die geboren zijn na ICSI vertonen dus een gevarieerder mitochondriaal genoom maar wat dit betekent moet nog verder onderzocht worden.

Bibliografie

G. D. Adamson, M. Tabangin, M. Macaluso, J. de Mouzon, The number of babies born globally after treatment with the assisted reproductive technologies (ART). Fertility and Sterility 100, S42-S42 (2013).

R. Hart, R. J. Norman, The longer-term health outcomes for children born as a result of IVF treatment: Part IGeneral health outcomes. Human Reproduction Update 19, 232-243 (2013).

F. Belva et al., Reproductive hormones of ICSI-conceived young adult men: the first results. Hum Reprod 32, 439-446 (2017).

M. Ceelen, M. M. van Weissenbruch, J. P. W. Vermeiden, F. E. van Leeuwen, H. A. Delemarre-van de Waal, Growth and development of children born after in vitro fertilization. Fertility and Sterility 90, 1662-1673 (2008).

C. Siristatidis et al., Mild Versus Conventional Ovarian Stimulation for Poor Responders Undergoing IVF/ICSI. In Vivo 31, 231-237 (2017).

G. Palermo, H. Joris, P. Devroey, A. C. Vansteirteghem, Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyteP. Lancet 340, 17-18 (1992).

J. L. Simpson, S. Rechitsky, Preimplantation diagnosis and other modern methods for prenatal diagnosis. Journal of Steroid Biochemistry and Molecular Biology 165, 124-130 (2017).

P. C. Steptoe, R. G. Edwards, Birth after reimplantation of a human embryo. Lancet 2, 366-366 (1978).

M. Hansen, C. Bower, E. Milne, N. de Klerk, J. J. Kurinczuk, Assisted reproductive technologies and the risk of birth defects - a systematic review. Human Reproduction 20, 328-338 (2005).

A. Pinborg, A. K. A. Henningsen, S. S. Malchau, A. Loft, Congenital anomalies after assisted reproductive technology. Fertility and Sterility 99, 327-332 (2013).

B. Fauser et al., Health outcomes of children born after IVF/ICSI: a review of current expert opinion and literature. Reproductive Biomedicine Online 28, 162-182 (2014).

M. Ceelen et al., Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8-18 years of IVF children and spontaneously conceived controls born to subfertile parents. Human Reproduction 24, 2788-2795 (2009).

R. C. Painter et al., Microalbuminuria in adults after prenatal exposure to the Dutch famine. Journal of the American Society of Nephrology 16, 189-194 (2005).

C. L. Abitbol, M. M. Rodriguez, The long-term renal and cardiovascular consequences of prematurity. Nature Reviews Nephrology 8, 265-274 (2012).

J. G. Eriksson, C. Osmond, E. Kajantie, T. J. Forsen, D. J. P. Barker, Patterns of growth among children who later develop type 2 diabetes or its risk factors. Diabetologia 49, 2853-2858 (2006).

D. J. P. Barker, C. Osmond, J. Golding, D. Kuh, M. E. J. Wadsworth, Growth in utero, blood-pressure in childhood and adult life, and mortality from cardiovascular-disease. British Medical Journal 298, 564-567 (1989).

R. W. J. Leunissen, G. F. Kerkhof, T. Stijnen, A. Hokken-Koelega, Timing and Tempo of First-Year Rapid Growth in Relation to Cardiovascular and Metabolic Risk Profile in Early Adulthood. Jama-Journal of the American Medical Association 301, 2234-2242 (2009).

F. Belva et al., Are ICSI adolescents at risk for increased adiposity? Human Reproduction 27, 257-264 (2012).

M. Ceelen, M. M. van Weissenbruch, J. P. W. Vermeiden, F. E. van Leeuwen, H. de Waal, Cardiometabolic differences in children born after in vitro fertilization: Follow-up study. Journal of Clinical Endocrinology & Metabolism 93, 1682-1688 (2008).

S. D. Sakka et al., Gender dimorphic increase in RBP-4 and NGAL in children born after IVF: an epigenetic phenomenon? European Journal of Clinical Investigation 43, 439-448 (2013).

U. Scherrer et al., Systemic and Pulmonary Vascular Dysfunction in Children Conceived by Assisted Reproductive Technologies. Circulation 125, 1890-1896 (2012).

B. Valenzuela-Alcaraz et al., Assisted Reproductive Technologies Are Associated With Cardiovascular Remodeling In Utero That Persists Postnatally. Circulation 128, 1442-1450 (2013).

T. K. Jensen et al., Fertility treatment and reproductive health of male offspring: A study of 1,925 young men from the general population. American Journal of Epidemiology 165, 583-590 (2007).

F. Belva et al., Semen quality of young adult ICSI offspring: the first results. Hum Reprod 31, 2811-2820 (2016).

F. Belva et al., Serum reproductive hormone levels and ultrasound findings in female offspring after intracytoplasmic sperm injection: first results. Fertil Steril,  (2017).

M. Ceelen, M. M. van Weissenbruch, J. P. W. Vermeiden, F. E. van Leeuwen, H. A. Delemarre-van de Waal, Pubertal development in children and adolescents born after IVF and spontaneous conception. Human Reproduction 23, 2791-2798 (2008).

H. Sasaki, Y. Matsui, Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nature Reviews Genetics 9, 129-140 (2008).

M. R. DeBaun, E. L. Niemitz, A. P. Feinberg, Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. American Journal of Human Genetics 72, 156-160 (2003).

A. C. Moll et al., Incidence of retinoblastoma in children born after in-vitro fertilisation. Lancet 361, 309-310 (2003).

G. Lazaraviciute, M. Kauser, S. Bhattacharya, P. Haggarty, A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously. Human Reproduction Update 20, 840-852 (2014).

V. F. Oliver et al., Defects in imprinting and genome-wide DNA methylation are not common in the in vitro fertilization population. Fertility and Sterility 97, 147-U219 (2012).

N. Whitelaw et al., Epigenetic status in the offspring of spontaneous and assisted conception. Human Reproduction 29, 1452-1458 (2014).

M. E. Doornbos, S. M. Maas, J. McDonnell, J. P. W. Vermeiden, R. C. M. Hennekam, Infertility, assisted reproduction technologies and imprinting disturbances: a Dutch study. Human Reproduction 22, 2476-2480 (2007).

C. D. Moyes, B. J. Battersby, S. C. Leary, Regulation of muscle mitochondrial design. Journal of Experimental Biology 201, 299-307 (1998).

S. Anderson et al., Sequence and organization of the human mitochondrial genome. Nature 290, 457-465 (1981).

E. A. Shoubridge, T. Wai, Mitochondrial DNA and the mammalian oocyte. Mitochondrion in the Germline and Early Development 77, 87-111 (2007).

X. J. Chen, R. A. Butow, The organization and inheritance of the mitochondrial genome. Nature Reviews Genetics 6, 815-825 (2005).

J. W. Taanman, The mitochondrial genome: structure, transcription, translation and replication. Biochimica Et Biophysica Acta-Bioenergetics 1410, 103-123 (1999).

H. Kasamatsu, J. Vinograd, Replication of circular DNA in eukaryotic cells. Annual Review of Biochemistry 43, 695-719 (1974).

D. C. Wallace, Mitochondrial DNA Mutations in Disease and Aging. Environmental and Molecular Mutagenesis 51, 440-450 (2010).

J. C. St John, J. Facucho-Oliveira, Y. Jiang, R. Kelly, R. Salah, Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring and embryonic stem cells. Human Reproduction Update 16, 488-509 (2010).

A. B. C. Otten, H. J. M. Smeets, Evolutionary defined role of the mitochondrial DNA in fertility, disease and ageing. Human Reproduction Update 21, 671-689 (2015).

M. Falkenberg et al., Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nature Genetics 31, 289-294 (2002).

N. D. Bonawitz, D. A. Clayton, G. S. Shadel, Initiation and beyond: Multiple functions of the human mitochondril transcription machinery. Molecular Cell 24, 813-825 (2006).

J. St John, The control of mtDNA replication during differentiation and development. Biochimica Et Biophysica Acta-General Subjects 1840, 1345-1354 (2014).

C. Yanicostas, N. Soussi-Yanicostas, R. El-Khoury, P. Benit, P. Rustin, Developmental aspects of respiratory chain from fetus to infancy. Seminars in Fetal & Neonatal Medicine 16, 175-180 (2011).

S. DiMauro, C. Garone, Metabolic disorders of fetal life: Glycogenoses and mitochondrial defects of the mitochondrial respiratory chain. Seminars in Fetal & Neonatal Medicine 16, 181-189 (2011).

J. M. Ross et al., Germline mitochondrial DNA mutations aggravate ageing and can impair brain development. Nature 501, 412-+ (2013).

J. C. von Kleist-Retzow et al., Antenatal manifestations of mitochondrial respiratory chain deficiency. Journal of Pediatrics 143, 208-212 (2003).

K. Gibson et al., Mitochondrial Oxidative Phosphorylation Disorders Presenting in Neonates: Clinical Manifestations and Enzymatic and Molecular Diagnoses. Pediatrics 122, 1003-1008 (2008).

M. V. Tavares et al., Antenatal manifestations of mitochondrial disorders. Journal of Inherited Metabolic Disease 36, 805-811 (2013).

K. G. Bensch, W. deGraaf, P. A. Hansen, H. P. Zassenhaus, J. A. Corbett, A transgenic model to study the pathogenesis of somatic mtDNA mutation accumulation in beta-cells. Diabetes Obesity & Metabolism 9, 74-80 (2007).

E. Fosslien, Review: Mitochondrial medicine - Molecular pathology of defective oxidative phosphorylation. Annals of Clinical and Laboratory Science 31, 25-67 (2001).

V. K. Mootha et al., Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell 115, 629-640 (2003).

M. E. Patti et al., Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proceedings of the National Academy of Sciences of the United States of America 100, 8466-8471 (2003).

J. A. Maassen et al., Mitochondrial diabetes - Molecular mechanisms and clinical presentation. Diabetes 53, S103-S109 (2004).

A. F. Whereat, Oxygen consumption of normal and atherosclerotic initima. Circulation Research 9, 571-& (1961).

J. Van Blerkom, Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion 11, 797-813 (2011).

Y. Bentov, T. Yavorska, N. Esfandiari, A. Jurisicova, R. F. Casper, The contribution of mitochondrial function to reproductive aging. Journal of Assisted Reproduction and Genetics 28, 773-783 (2011).

A. K. Bartmann, G. S. Romao, E. D. Ramos, R. A. Ferriani, Why do older women have poor implantation rates? A possible role of the mitochondria. Journal of Assisted Reproduction and Genetics 21, 79-83 (2004).

U. Eichenlaub-Ritter, M. Wieczorek, S. Luke, T. Seidel, Age related changes in mitochondrial function and new approaches to study redox regulation in mammalian oocytes in response to age or maturation conditions. Mitochondrion 11, 783-796 (2011).

B. A. I. Payne et al., Universal heteroplasmy of human mitochondrial DNA. Human Molecular Genetics 22, 384-390 (2013).

K. X. Ye, J. Lu, F. Ma, A. Keinan, Z. L. Gu, Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals. Proceedings of the National Academy of Sciences of the United States of America 111, 10654-10659 (2014).

Y. Guo et al., Very Low-Level Heteroplasmy mtDNA Variations Are Inherited in Humans. Journal of Genetics and Genomics 40, 607-615 (2013).

P. Reynier et al., Mitochondrial DNA content affects the fertilizability of human oocytes. Molecular Human Reproduction 7, 425-429 (2001).

T. Wai et al., The Role of Mitochondrial DNA Copy Number in Mammalian Fertility. Biology of Reproduction 83, 52-62 (2010).

J. Steffann, S. Monnot, J. P. Bonnefont, mtDNA mutations variously impact mtDNA maintenance throughout the human embryofetal development. Clinical Genetics 88, 416-424 (2015).

J. A. Barritt, C. A. Brenner, J. Cohen, D. W. Matt, Mitochondrial DNA rearrangements in human oocytes and embryos. Molecular Human Reproduction 5, 927-933 (1999).

H. T. Chao et al., Repeated ovarian stimulations induce oxidative damage and mitochondrial DNA mutations in mouse ovaries. Role of the Mitochondria in Human Aging and Disease: from Genes to Cell Signaling 1042, 148-156 (2005).

T. C. Gibson, H. M. Kubisch, C. A. Brenner, Mitochondrial DNA deletions in rhesus macaque oocytes and embryos. Molecular Human Reproduction 11, 785-789 (2005).

H. S. Ge et al., Impaired mitochondrial function in murine oocytes is associated with controlled ovarian hyperstimulation and in vitro maturation. Reproduction Fertility and Development 24, 945-952 (2012).

E. R. Hammond et al., Oocyte mitochondrial deletions and heteroplasmy in a bovine model of ageing and ovarian stimulation. Molecular Human Reproduction 22, 261-271 (2016).

R. B. Blok, D. A. Gook, D. R. Thorburn, H. H. M. Dahl, Skewed segregation of the mtDNA nt 8993 (T->G) mutation in human oocytes. American Journal of Human Genetics 60, 1495-1501 (1997).

D. T. Brown, D. C. Samuels, E. M. Michael, D. M. Turnbull, P. F. Chinnery, Random genetic drift determines the level of mutant mtDNA in human primary oocytes. American Journal of Human Genetics 68, 533-536 (2001).

R. P. S. Jansen, K. de Boer, The bottleneck: mitochondrial imperatives in oogenesis and ovarian follicular fate. Molecular and Cellular Endocrinology 145, 81-88 (1998).

H. J. Leese, A. M. Barton, Pyruvate and glucose-uptake by mouse ova and preimplantation embryos. Journal of Reproduction and Fertility 72, 9-13 (1984).

J. Van Blerkom, P. Davis, V. Mathwig, S. Alexander, Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos. Human Reproduction 17, 393-406 (2002).

L. Piko, K. D. Taylor, Amounts of mitochondrial-DNA and abundance of some mitochondrial gene transcripts in early mouse embryos. Developmental Biology 123, 364-374 (1987).

L. Piko, L. Matsumoto, Number of mitochondria and some properties of mitochondrial-DNA in mouse egg. Developmental Biology 49, 1-10 (1976).

E. C. Spikings, J. Alderson, J. C. S. John, Regulated mitochondrial DNA replication during oocyte maturation is essential for successful porcine embryonic development. Biology of Reproduction 76, 327-335 (2007).

L. Q. Cao et al., The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells. Nature Genetics 39, 386-390 (2007).

J. Van Blerkom, P. Davis, S. Alexander, Differential mitochondrial distribution in human pronuclear embryos leads to disproportionate inheritance between blastomeres: relationship to microtubular organization, ATP content and competence. Human Reproduction 15, 2621-2633 (2000).

J. A. Thomson et al., Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147 (1998).

C. D. L. Folmes, P. P. Dzeja, T. J. Nelson, A. Terzic, Metabolic Plasticity in Stem Cell Homeostasis and Differentiation. Cell Stem Cell 11, 596-606 (2012).

X. L. Xu et al., Mitochondrial Regulation in Pluripotent Stem Cells. Cell Metabolism 18, 325-332 (2013).

K. J. Ahlqvist et al., Somatic Progenitor Cell Vulnerability to Mitochondrial DNA Mutagenesis Underlies Progeroid Phenotypes in Polg Mutator Mice. Cell Metabolism 15, 100-109 (2012).

S. Chung et al., Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells. Nat Clin Pract Cardiovasc Med 4 Suppl 1, S60-67 (2007).

S. Mandal, A. G. Lindgren, A. S. Srivastava, A. T. Clark, U. Banerjee, Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells. Stem Cells 29, 486-495 (2011).

K. Takahashi, S. Yamanaka, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676 (2006).

K. Takahashi et al., Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872 (2007).

J. M. Facucho-Oliveira, J. C. St John, The relationship between pluripotency and mitochondrial DNA proliferation during early embryo development and embryonic stem cell differentiation. Stem Cell Rev 5, 140-158 (2009).

A. Prigione et al., Human Induced Pluripotent Stem Cells Harbor Homoplasmic and Heteroplasmic Mitochondrial DNA Mutations While Maintaining Human Embryonic Stem Cell-like Metabolic Reprogramming. Stem Cells 29, 1338-1348 (2011).

S. Varum et al., Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS One 6, e20914 (2011).

M. Wahlestedt et al., Somatic Cells with a Heavy Mitochondrial DNA Mutational Load Render Induced Pluripotent Stem Cells with Distinct Differentiation Defects. Stem Cells 32, 1173-1182 (2014).

M. Yokota, H. Hatakeyama, S. Okabe, Y. Ono, Y. I. Goto, Mitochondrial respiratory dysfunction caused by a heteroplasmic mitochondrial DNA mutation blocks cellular reprogramming. Human Molecular Genetics 24, 4698-4709 (2015).

M. Yokota, H. Hatakeyama, Y. Ono, M. Kanazawa, Y. Goto, Mitochondrial respiratory dysfunction disturbs neuronal and cardiac lineage commitment of human iPSCs. Cell Death & Disease 8, 11 (2017).

A. Trifunovic et al., Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429, 417-423 (2004).

A. M. Schaefer, R. W. Taylor, D. M. Turnbull, P. F. Chinnery, The epidemiology of mitochondrial disorders - past, present and future. Biochimica Et Biophysica Acta-Bioenergetics 1659, 115-120 (2004).

S. W. Ballinger, Mitochondrial dysfunction in cardiovascular disease. Free Radical Biology and Medicine 38, 1278-1295 (2005).

A. Rotig, T. Bourgeron, D. Chretien, P. Rustin, A. Munnich, Spectrum of mitochondrial-DNA rearrangements in the Pearson marrow pancreas syndrome. American Journal of Human Genetics 57, 1047-1047 (1995).

I. J. Holt, A. E. Harding, R. K. H. Petty, J. A. Morganhughes, A new mitochondrial disease associated with mitochondrial-DNA heteroplasmy. American Journal of Human Genetics 46, 428-433 (1990).

A. L. Andreu et al., Missense mutation in the mtDNA cytochrome b gene in a patient with myopathy. Neurology 51, 1444-1447 (1998).

A. Rojo et al., NARP-MILS syndrome caused by 8993 T > G mitochondrial DNA mutation: a clinical, genetic and neuropathological study. Acta Neuropathologica 111, 610-616 (2006).

F. G. Debray, M. Lambert, A. Lortie, M. Vanasse, G. A. Mitchell, Long-term outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation. American Journal of Medical Genetics Part A 143A, 2046-2051 (2007).

Y. Goto, I. Nonaka, S. Horai, A mutation in the transfer RNALEU(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348, 651-653 (1990).

C. Enter et al., A specific point mutation in the mitochondrial genome of caucasians with MELAS. Human Genetics 88, 233-236 (1991).

L. Z. Diba, S. M. M. Ardebili, J. Gharesouran, M. Houshmand, Age-related decrease in mtDNA content as a consequence of mtDNA 4977 bp deletion. Mitochondrial DNA Part A 27, 3008-3012 (2016).

A. A. Kazuno et al., Identification of mitochondrial DNA polymorphisms that alter mitochondrial matrix pH and intracellular calcium dynamics. Plos Genetics 2, 1167-1177 (2006).

M. A. Frye et al., Mitochondrial DNA sequence data reveals association of haplogroup U with psychosis in bipolar disorder. Journal of Psychiatric Research 84, 221-226 (2017).

S. Farha et al., Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension. Plos One 11, 13 (2016).

H. W. Wang, Y. Xu, Y. L. Miao, H. Y. Luo, K. H. Wang, Mitochondrial DNA Haplogroup A may confer a genetic susceptibility to AIDS group from Southwest China. Mitochondrial DNA Part A 27, 2221-2224 (2016).

G. A. Cortopassi, N. Arnheim, Detection of a specific mitochondrial-DNA deletion in tissues of older humans. Nucleic Acids Research 18, 6927-6933 (1990).

M. Debrinski, M. T. Lott, J. M. Shoffner, D. C. Wallace, Accumulation of mitochondrial-DNA damage in chronic heart and brain disease. American Journal of Human Genetics 49, 132-132 (1991).

L. C. Greaves, A. K. Reeve, R. W. Taylor, D. M. Turnbull, Mitochondrial DNA and disease. Journal of Pathology 226, 274-286 (2012).

D. C. Wallace, D. Chalkia, Mitochondrial DNA Genetics and the Heteroplasmy Conundrum in Evolution and Disease. Cold Spring Harbor Perspectives in Biology 5, 47 (2013).

D. C. Samuels et al., Recurrent Tissue-Specific mtDNA Mutations Are Common in Humans. Plos Genetics 9, 12 (2013).

E. A. Schon, S. DiMauro, M. Hirano, Human mitochondrial DNA: roles of inherited and somatic mutations. Nature Reviews Genetics 13, 878-890 (2012).

A. Chomyn, G. Attardi, MtDNA mutations in aging and apoptosis. Biochemical and Biophysical Research Communications 304, 519-529 (2003).

M. K. Li, R. Schroder, S. Y. Ni, B. Madea, M. Stoneking, Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations. Proceedings of the National Academy of Sciences of the United States of America 112, 2491-2496 (2015).

F. Ye, D. C. Samuels, T. Clark, Y. Guo, High-throughput sequencing in mitochondrial DNA research. Mitochondrion 17, 157-163 (2014).

V. Vasta, S. B. Ng, E. H. Turner, J. Shendure, S. H. Hahn, Targeted gene analysis of mitochondrial disorders by next generation sequencing. Molecular Genetics and Metabolism 98, 6-6 (2009).

M. X. Sosa et al., Next-Generation Sequencing of Human Mitochondrial Reference Genomes Uncovers High Heteroplasmy Frequency. Plos Computational Biology 8, 11 (2012).

R. K. Bai, L. J. C. Wong, Detection and quantification of heteroplasmic mutant mitochondrial DNA by real-time amplification refractory mutation system quantitative PCR analysis: A single-step approach. Clinical Chemistry 50, 996-1001 (2004).

M. H. Liang, L. J. C. Wong, Yield of mtDNA mutation analysis in 2,000 patients. American Journal of Medical Genetics 77, 395-400 (1998).

A. Rohlin et al., Parallel Sequencing Used in Detection of Mosaic Mutations: Comparison With Four Diagnostic DNA Screening Techniques. Human Mutation 30, 1012-1020 (2009).

W. Zhang, H. Cui, L. J. C. Wong, Comprehensive One-Step Molecular Analyses of Mitochondrial Genome by Massively Parallel Sequencing. Clinical Chemistry 58, 1322-1331 (2012).

H. P. J. Buermans, J. T. den Dunnen, Next generation sequencing technology: Advances and applications. Biochimica Et Biophysica Acta-Molecular Basis of Disease 1842, 1932-1941 (2014).

R. D. Mitra, G. M. Church, In situ localized amplification and contact replication of many individual DNA molecules. Nucleic Acids Research 27, 6 (1999).

H. Li, R. Durbin, Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754-1760 (2009).

L. Heng, C. C. Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA, Ed. (Oxford University Press 2013, 2013).

M. K. Li et al., Detecting Heteroplasmy from High-Throughput Sequencing of Complete Human Mitochondrial DNA Genomes. American Journal of Human Genetics 87, 237-249 (2010).

Y. Guo et al., The use of next generation sequencing technology to study the effect of radiation therapy on mitochondrial DNA mutation. Mutation Research-Genetic Toxicology and Environmental Mutagenesis 744, 154-160 (2012).

I. Mateizel et al., Derivation of human embryonic stem cell lines from embryos obtained after IVF and after PGD for monogenic disorders. Human Reproduction 21, 503-511 (2006).

I. Mateizel, C. Spits, M. De Rycke, I. Liebaers, K. Sermon, Derivation, culture, and characterization of VUB hESC lines. In Vitro Cellular & Developmental Biology-Animal 46, 300-308 (2010).

K. Cibulskis et al., Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nature Biotechnology 31, 213-219 (2013).

J. Knez et al., Correlates of Peripheral Blood Mitochondrial DNA Content in a General Population. American Journal of Epidemiology 183, 138-146 (2016).

S. Lopez et al., Sex-Specific Regulation of Mitochondrial DNA Levels: Genome-Wide Linkage Analysis to Identify Quantitative Trait Loci. Plos One 7, 11 (2012).

U. Roostalu et al., Origin and expansion of haplogroup H, the dominant human mitochondrial DNA lineage in West Eurasia: The near eastern and Caucasian perspective. Molecular Biology and Evolution 24, 436-448 (2007).

M. Pala et al., Mitochondrial DNA Signals of Late Glacial Recolonization of Europe from Near Eastern Refugia. American Journal of Human Genetics 90, 915-924 (2012).

A. Marcuello et al., Human mitochondrial variants influence on oxygen consumption. Mitochondrion 9, 27-30 (2009).

A. Gomez-Duran et al., Oxidative phosphorylation differences between mitochondrial DNA haplogroups modify the risk of Leber's hereditary optic neuropathy. Biochimica Et Biophysica Acta-Molecular Basis of Disease 1822, 1216-1222 (2012).

E. J. Bowles et al., Contrasting effects of in vitro fertilization and nuclear transfer on the expression of mtDNA replication factors. Genetics 176, 1511-1526 (2007).

E. J. Kang et al., Age-Related Accumulation of Somatic Mitochondrial DNA Mutations in Adult-Derived Human iPSCs. Cell Stem Cell 18, 625-636 (2016).

Universiteit of Hogeschool
Master in de Biomedische Wetenschappen
Publicatiejaar
2017
Promotor(en)
Prof. Dr. Claudia Spits
Kernwoorden
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