Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
11 2022
Historique:
received: 09 01 2022
accepted: 29 08 2022
pubmed: 6 10 2022
medline: 5 11 2022
entrez: 5 10 2022
Statut: ppublish

Résumé

DNA transfer from cytoplasmic organelles to the cell nucleus is a legacy of the endosymbiotic event-the majority of nuclear-mitochondrial segments (NUMTs) are thought to be ancient, preceding human speciation

Identifiants

pubmed: 36198798
doi: 10.1038/s41586-022-05288-7
pii: 10.1038/s41586-022-05288-7
pmc: PMC9630118
doi:

Substances chimiques

DNA, Mitochondrial 0
PRDM9 protein, human EC 2.1.1.43

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

105-114

Subventions

Organisme : Wellcome Trust
ID : 212219/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council UK
Organisme : Medical Research Council
ID : MC_UP_1501/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S035699/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S005021/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00015/9
Pays : United Kingdom
Organisme : Wellcome Trust
ID : RPG-2018-408
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00028/7
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13047
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M008886/1
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

Références

Roger, A. J., Munoz-Gomez, S. A. & Kamikawa, R. The origin and diversification of mitochondria. Curr. Biol. 27, R1177–R1192 (2017).
pubmed: 29112874 doi: 10.1016/j.cub.2017.09.015
Gray, M. W., Burger, G. & Lang, B. F. Mitochondrial evolution. Science 283, 1476–1481 (1999).
pubmed: 10066161 doi: 10.1126/science.283.5407.1476
Hazkani-Covo, E., Zeller, R. M. & Martin, W. Molecular poltergeists: mitochondrial DNA copies (numts) in sequenced nuclear genomes. PLoS Genet. 6, e1000834 (2010).
pubmed: 20168995 pmcid: 2820518 doi: 10.1371/journal.pgen.1000834
Lopez, J. V., Yuhki, N., Masuda, R., Modi, W. & O'Brien, S. J. Numt, a recent transfer and tandem amplification of mitochondrial DNA to the nuclear genome of the domestic cat. J. Mol. Evol. 39, 174–190 (1994).
pubmed: 7932781 doi: 10.1007/BF00163806
Wei, W. et al. Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans. Nat. Commun. 11, 1740 (2020).
pubmed: 32269217 pmcid: 7142097 doi: 10.1038/s41467-020-15336-3
Willett-Brozick, J. E., Savul, S. A., Richey, L. E. & Baysal, B. E. Germ line insertion of mtDNA at the breakpoint junction of a reciprocal constitutional translocation. Hum. Genet. 109, 216–223 (2001).
pubmed: 11511928 doi: 10.1007/s004390100564
Borensztajn, K. et al. Characterization of two novel splice site mutations in human factor VII gene causing severe plasma factor VII deficiency and bleeding diathesis. Br. J. Haematol. 117, 168–171 (2002).
pubmed: 11918550 doi: 10.1046/j.1365-2141.2002.03397.x
Turner, C. et al. Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer. Hum. Genet. 112, 303–309 (2003).
pubmed: 12545275 doi: 10.1007/s00439-002-0892-2
Ahmed, Z. M. et al. Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC. Hum. Genet. 110, 527–531 (2002).
pubmed: 12107438 doi: 10.1007/s00439-002-0732-4
Pagnamenta, A. T., Wei, W., Rahman, S. & Chinnery, P. F. Biparental inheritance of mitochondrial DNA revisited. Nat. Rev. Genet. 22, 477–478 (2021).
pubmed: 34031572 doi: 10.1038/s41576-021-00380-6
Luo, S. et al. Biparental inheritance of mitochondrial DNA in humans. Proc. Natl Acad. Sci. USA 115, 13039–13044 (2018).
pubmed: 30478036 pmcid: 6304937 doi: 10.1073/pnas.1810946115
Maude, H. et al. NUMT confounding biases mitochondrial heteroplasmy calls in favor of the reference allele. Front. Cell. Dev. Biol. 7, 201 (2019).
pubmed: 31612134 pmcid: 6773831 doi: 10.3389/fcell.2019.00201
Salas, A., Schonherr, S., Bandelt, H. J., Gomez-Carballa, A. & Weissensteiner, H. Extraordinary claims require extraordinary evidence in asserted mtDNA biparental inheritance. Forensic Sci. Int. Genet. 47, 102274 (2020).
pubmed: 32330850 doi: 10.1016/j.fsigen.2020.102274
Smedley, D. et al. 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care—preliminary report. N. Engl. J. Med. 385, 1868–1880 (2021).
pubmed: 34758253 doi: 10.1056/NEJMoa2035790
Ju, Y. S. et al. Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells. Genome Res. 25, 814–824 (2015).
pubmed: 25963125 pmcid: 4448678 doi: 10.1101/gr.190470.115
Simone, D., Calabrese, F. M., Lang, M., Gasparre, G. & Attimonelli, M. The reference human nuclear mitochondrial sequences compilation validated and implemented on the UCSC genome browser. BMC Genomics 12, 517 (2011).
pubmed: 22013967 pmcid: 3228558 doi: 10.1186/1471-2164-12-517
Calabrese, F. M., Simone, D. & Attimonelli, M. Primates and mouse NumtS in the UCSC Genome Browser. BMC Bioinf. 13, S15 (2012).
doi: 10.1186/1471-2105-13-S4-S15
Li, M., Schroeder, R., Ko, A. & Stoneking, M. Fidelity of capture-enrichment for mtDNA genome sequencing: influence of NUMTs. Nucleic Acids Res. 40, e137 (2012).
pubmed: 22649055 pmcid: 3467033 doi: 10.1093/nar/gks499
Dayama, G., Emery, S. B., Kidd, J. M. & Mills, R. E. The genomic landscape of polymorphic human nuclear mitochondrial insertions. Nucleic Acids Res. 42, 12640–12649 (2014).
pubmed: 25348406 pmcid: 4227756 doi: 10.1093/nar/gku1038
Gigante, S. et al. Using long-read sequencing to detect imprinted DNA methylation. Nucleic Acids Res. 47, e46 (2019).
pubmed: 30793194 pmcid: 6486641 doi: 10.1093/nar/gkz107
Bicci, I., Calabrese, C., Golder, Z. J., Gomez-Duran, A. & Chinnery, P. F. Single-molecule mitochondrial DNA sequencing shows no evidence of CpG methylation in human cells and tissues. Nucleic Acids Res. 49, 12757–12768 (2021).
pubmed: 34850165 pmcid: 8682748 doi: 10.1093/nar/gkab1179
Huang, C. Y., Grunheit, N., Ahmadinejad, N., Timmis, J. N. & Martin, W. Mutational decay and age of chloroplast and mitochondrial genomes transferred recently to angiosperm nuclear chromosomes. Plant Physiol. 138, 1723–1733 (2005).
pubmed: 15951485 pmcid: 1176441 doi: 10.1104/pp.105.060327
Ju, Y. S. et al. Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer. eLife 3, e02935 (2014).
pmcid: 4371858 doi: 10.7554/eLife.02935
Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016).
pubmed: 27535533 pmcid: 5018207 doi: 10.1038/nature19057
Genovese, G. et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N. Engl. J. Med. 371, 2477–2487 (2014).
pubmed: 25426838 pmcid: 4290021 doi: 10.1056/NEJMoa1409405
Yuan, Y. et al. Comprehensive molecular characterization of mitochondrial genomes in human cancers. Nat. Genet. 52, 342–352 (2020).
pubmed: 32024997 pmcid: 7058535 doi: 10.1038/s41588-019-0557-x
Samuels, D. C., Schon, E. A. & Chinnery, P. F. Two direct repeats cause most human mtDNA deletions. Trends Genet. 20, 393–398 (2004).
pubmed: 15313545 doi: 10.1016/j.tig.2004.07.003
Sondka, Z. et al. The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers. Nat. Rev. Cancer 18, 696–705 (2018).
pubmed: 30293088 pmcid: 6450507 doi: 10.1038/s41568-018-0060-1
Matsuyama, A. et al. Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2: evolutionarily conserved but highly recombinogenic. Proc. Natl Acad. Sci. USA 100, 14988–14993 (2003).
pubmed: 14630947 pmcid: 299872 doi: 10.1073/pnas.2336256100
Goransson, M. et al. The myxoid liposarcoma FUS–DDIT3 fusion oncoprotein deregulates NF-κB target genes by interaction with NFKBIZ. Oncogene 28, 270–278 (2009).
pubmed: 18850010 doi: 10.1038/onc.2008.378
Qin, S. et al. DSG2 expression is correlated with poor prognosis and promotes early-stage cervical cancer. Cancer Cell Int. 20, 206 (2020).
pubmed: 32514251 pmcid: 7268232 doi: 10.1186/s12935-020-01292-x
Rao, X. et al. MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways. Oncogene 30, 1082–1097 (2011).
pubmed: 21057537 doi: 10.1038/onc.2010.487
Blanchard, J. L. & Schmidt, G. W. Mitochondrial DNA migration events in yeast and humans: integration by a common end-joining mechanism and alternative perspectives on nucleotide substitution patterns. Mol. Biol. Evol. 13, 893 (1996).
pubmed: 8754225 doi: 10.1093/oxfordjournals.molbev.a025650
Ricchetti, M., Tekaia, F. & Dujon, B. Continued colonization of the human genome by mitochondrial DNA. PLoS Biol. 2, E273 (2004).
pubmed: 15361937 pmcid: 515365 doi: 10.1371/journal.pbio.0020273
Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94–101 (2020).
pubmed: 32025018 pmcid: 7054213 doi: 10.1038/s41586-020-1943-3
Seplyarskiy, V. B. et al. APOBEC-induced mutations in human cancers are strongly enriched on the lagging DNA strand during replication. Genome Res. 26, 174–182 (2016).
pubmed: 26755635 pmcid: 4728370 doi: 10.1101/gr.197046.115
Myers, S. et al. Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination. Science 327, 876–879 (2010).
pubmed: 20044541 doi: 10.1126/science.1182363
Wood, R. D., Mitchell, M. & Lindahl, T. Human DNA repair genes, 2005. Mutat. Res. 577, 275–283 (2005).
pubmed: 15922366 doi: 10.1016/j.mrfmmm.2005.03.007
Wood, R. D., Mitchell, M., Sgouros, J. & Lindahl, T. Human DNA repair genes. Science 291, 1284–1289 (2001).
pubmed: 11181991 doi: 10.1126/science.1056154
Hazkani-Covo, E., Sorek, R. & Graur, D. Evolutionary dynamics of large numts in the human genome: rarity of independent insertions and abundance of post-insertion duplications. J. Mol. Evol. 56, 169–174 (2003).
pubmed: 12574863 doi: 10.1007/s00239-002-2390-5
Li, Y. et al. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 508, 98–102 (2014).
pubmed: 24670643 pmcid: 3976272 doi: 10.1038/nature13115
Bensasson, D., Feldman, M. W. & Petrov, D. A. Rates of DNA duplication and mitochondrial DNA insertion in the human genome. J. Mol. Evol. 57, 343–354 (2003).
pubmed: 14629044 doi: 10.1007/s00239-003-2485-7
Gustafsson, C. M., Falkenberg, M. & Larsson, N. G. Maintenance and expression of mammalian mitochondrial DNA. Annu. Rev. Biochem. 85, 133–160 (2016).
pubmed: 27023847 doi: 10.1146/annurev-biochem-060815-014402
McArthur, K. et al. BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science 359, eaao6047 (2018).
pubmed: 29472455 doi: 10.1126/science.aao6047
Tigano, M., Vargas, D. C., Tremblay-Belzile, S., Fu, Y. & Sfeir, A. Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance. Nature 591, 477–481 (2021).
pubmed: 33627873 doi: 10.1038/s41586-021-03269-w
Caulfield, M. et al. The national genomics research and healthcare knowledgebase. figshare https://doi.org/10.6084/m9.figshare.4530893.v5 (2019).
Jun, G. et al. Detecting and estimating contamination of human DNA samples in sequencing and array-based genotype data. Am. J. Hum. Genet. 91, 839–848 (2012).
pubmed: 23103226 pmcid: 3487130 doi: 10.1016/j.ajhg.2012.09.004
Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).
pubmed: 25722852 pmcid: 4342193 doi: 10.1186/s13742-015-0047-8
Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
pubmed: 20110278 pmcid: 2832824 doi: 10.1093/bioinformatics/btq033
Wei, W. et al. Germline selection shapes human mitochondrial DNA diversity. Science 364, eaau6520 (2019).
pubmed: 31123110 doi: 10.1126/science.aau6520
The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature 526, 68–74 (2015).
doi: 10.1038/nature15393
Conomos, M. P., Reiner, A. P., Weir, B. S. & Thornton, T. A. Model-free estimation of recent genetic relatedness. Am. J. Hum. Genet. 98, 127–148 (2016).
pubmed: 26748516 pmcid: 4716688 doi: 10.1016/j.ajhg.2015.11.022
Bergmann, E. A., Chen, B. J., Arora, K., Vacic, V. & Zody, M. C. Conpair: concordance and contamination estimator for matched tumor-normal pairs. Bioinformatics 32, 3196–3198 (2016).
pubmed: 27354699 pmcid: 5048070 doi: 10.1093/bioinformatics/btw389
Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82 (2011).
pubmed: 21167468 pmcid: 3014363 doi: 10.1016/j.ajhg.2010.11.011
McInnes, L., Healy, J. & Melville, J. UMAP: uniform manifold approximation and projection for dimension reduction. Preprint at https://arxiv.org/abs/1802.03426 (2020).
John, C. R. et al. M3C: Monte Carlo reference-based consensus clustering. Sci. Rep. 10, 1816 (2020).
pubmed: 32020004 pmcid: 7000518 doi: 10.1038/s41598-020-58766-1
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
pubmed: 19505943 pmcid: 2723002 doi: 10.1093/bioinformatics/btp352
Calabrese, C. et al. MToolBox: a highly automated pipeline for heteroplasmy annotation and prioritization analysis of human mitochondrial variants in high-throughput sequencing. Bioinformatics 30, 3115–3117 (2014).
pubmed: 25028726 pmcid: 4201154 doi: 10.1093/bioinformatics/btu483
Koboldt, D. C. et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 22, 568–576 (2012).
pubmed: 22300766 pmcid: 3290792 doi: 10.1101/gr.129684.111
van Oven, M. & Kayser, M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum. Mutat. 30, E386–E394 (2009).
pubmed: 18853457 doi: 10.1002/humu.20921
Weissensteiner, H. et al. HaploGrep 2: mitochondrial haplogroup classification in the era of high-throughput sequencing. Nucleic Acids Res. 44, W58–W63 (2016).
pubmed: 27084951 pmcid: 4987869 doi: 10.1093/nar/gkw233
Faust, G. G. & Hall, I. M. SAMBLASTER: fast duplicate marking and structural variant read extraction. Bioinformatics 30, 2503–2505 (2014).
pubmed: 24812344 pmcid: 4147885 doi: 10.1093/bioinformatics/btu314
Kent, W. J. BLAT-the BLAST-like alignment tool. Genome Res. 12, 656–664 (2002).
pubmed: 11932250 pmcid: 187518
Frankish, A. et al. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res. 47, D766–D773 (2019).
pubmed: 30357393 doi: 10.1093/nar/gky955
Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434–443 (2020).
pubmed: 32461654 pmcid: 7334197 doi: 10.1038/s41586-020-2308-7
Kent, W. J. et al. The human genome browser at UCSC. Genome Res. 12, 996–1006 (2002).
pubmed: 12045153 pmcid: 186604 doi: 10.1101/gr.229102
Kogelnik, A. M., Lott, M. T., Brown, M. D., Navathe, S. B. & Wallace, D. C. MITOMAP: a human mitochondrial genome database. Nucleic Acids Res. 24, 177–179 (1996).
pubmed: 8594574 pmcid: 145607 doi: 10.1093/nar/24.1.177
R Core Team. A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2019).
Damas, J., Carneiro, J., Amorim, A. & Pereira, F. MitoBreak: the mitochondrial DNA breakpoints database. Nucleic Acids Res. 42, D1261–D1268 (2014).
pubmed: 24170808 doi: 10.1093/nar/gkt982
Raczy, C. et al. Isaac: ultra-fast whole-genome secondary analysis on Illumina sequencing platforms. Bioinformatics 29, 2041–2043 (2013).
pubmed: 23736529 doi: 10.1093/bioinformatics/btt314
Kim, S. et al. Strelka2: fast and accurate calling of germline and somatic variants. Nat. Methods 15, 591–594 (2018).
pubmed: 30013048 doi: 10.1038/s41592-018-0051-x
Chen, X. et al. Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications. Bioinformatics 32, 1220–1222 (2016).
pubmed: 26647377 doi: 10.1093/bioinformatics/btv710
Roller, E., Ivakhno, S., Lee, S., Royce, T. & Tanner, S. Canvas: versatile and scalable detection of copy number variants. Bioinformatics 32, 2375–2377 (2016).
pubmed: 27153601 doi: 10.1093/bioinformatics/btw163
Altemose, N. et al. A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis. eLife 6, e28383 (2017).
pubmed: 29072575 pmcid: 5705219 doi: 10.7554/eLife.28383
Alexandrov, L. B., Nik-Zainal, S., Wedge, D. C., Campbell, P. J. & Stratton, M. R. Deciphering signatures of mutational processes operative in human cancer. Cell Rep. 3, 246–259 (2013).
pubmed: 23318258 pmcid: 3588146 doi: 10.1016/j.celrep.2012.12.008
Martin, A. R. et al. PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nat. Genet. 51, 1560–1565 (2019).
pubmed: 31676867 doi: 10.1038/s41588-019-0528-2
Hamosh, A., Scott, A. F., Amberger, J., Valle, D. & McKusick, V. A. Online Mendelian Inheritance in Man (OMIM). Hum Mutat 15, 57–61 (2000).
pubmed: 10612823 doi: 10.1002/(SICI)1098-1004(200001)15:1<57::AID-HUMU12>3.0.CO;2-G
Adam, M. P. et al. in GeneReviews (eds El-Hattab, A. W. et al.) Mitochondrial DNA maintenance defects overview. (University of Washington, 1993).
Schon, K. R. et al. Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study. Brit. Med. J. 375, e066288 (2021).
pubmed: 34732400 pmcid: 8565085 doi: 10.1136/bmj-2021-066288
Li, H. Minimap2: pairwise alignment for nucleotide sequences. Bioinformatics 34, 3094–3100 (2018).
pubmed: 29750242 pmcid: 6137996 doi: 10.1093/bioinformatics/bty191
De Coster, W., D'Hert, S., Schultz, D. T., Cruts, M. & Van Broeckhoven, C. NanoPack: visualizing and processing long-read sequencing data. Bioinformatics 34, 2666–2669 (2018).
pubmed: 29547981 pmcid: 6061794 doi: 10.1093/bioinformatics/bty149
Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24–26 (2011).
pubmed: 21221095 pmcid: 3346182 doi: 10.1038/nbt.1754
Loman, N. J., Quick, J. & Simpson, J. T. A complete bacterial genome assembled de novo using only nanopore sequencing data. Nat. Methods 12, 733–735 (2015).
pubmed: 26076426 doi: 10.1038/nmeth.3444
Huang, X. & Madan, A. CAP3: A DNA sequence assembly program. Genome Res. 9, 868–877 (1999).
pubmed: 10508846 pmcid: 310812 doi: 10.1101/gr.9.9.868
Andrews, R. M. et al. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat. Genet. 23, 147 (1999).
pubmed: 10508508 doi: 10.1038/13779
Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).
pubmed: 21988835 pmcid: 3261699 doi: 10.1038/msb.2011.75
Cock, P. J. et al. Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 25, 1422–1423 (2009).
pubmed: 19304878 pmcid: 2682512 doi: 10.1093/bioinformatics/btp163
Krzywinski, M. et al. Circos: an information aesthetic for comparative genomics. Genome Res. 19, 1639–1645 (2009).
pubmed: 19541911 pmcid: 2752132 doi: 10.1101/gr.092759.109
Anand, L. & Rodriguez Lopez, C. M. ChromoMap: an R package for interactive visualization of multi-omics data and annotation of chromosomes. BMC Bioinformatics 23, 33 (2022).
pubmed: 35016614 pmcid: 8753883 doi: 10.1186/s12859-021-04556-z
Wang, J. et al. dbRIP: A highly integrated database of retrotransposon insertion polymorphisms in humans. Hum. Mutat. 27, 323–329 (2006).
Köhler, S. et al. The human phenotype ontology in 2021. Nucleic Acids Res. 49, D1207–D1217 (2020).
Winston Chang et al. shiny: Web Application Framework for R. R package version 1.7.1. https://CRAN.R-project.org/package=shiny (2021).

Auteurs

Wei Wei (W)

Department of Clinical Neuroscience, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.

Katherine R Schon (KR)

Department of Clinical Neuroscience, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge, UK.

Greg Elgar (G)

Genomics England, London, UK.

Andrea Orioli (A)

Genomics England, London, UK.

Melanie Tanguy (M)

Genomics England, London, UK.

Adam Giess (A)

Genomics England, London, UK.

Marc Tischkowitz (M)

Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge, UK.

Mark J Caulfield (MJ)

William Harvey Research Institute, Queen Mary University of London, London, UK.

Patrick F Chinnery (PF)

Department of Clinical Neuroscience, School of Clinical Medicine, University of Cambridge, Cambridge, UK. pfc25@cam.ac.uk.
Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK. pfc25@cam.ac.uk.

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