Somatic Mutagenesis in Mammals and Its Implications for Human Disease and Aging

Literature Cited

1. 1.  Abyzov A, Mariani J, Palejev D, Zhang Y, Haney MS et al. 2012. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature 492:438–42
   [Google Scholar]
2. 2.  Abyzov A, Tomasini L, Zhou B, Vasmatzis N, Coppola G et al. 2017. One thousand somatic SNVs per skin fibroblast cell set baseline of mosaic mutational load with patterns that suggest proliferative origin. Genome Res 27:512–23
   [Google Scholar]
3. 3.  Albertini RJ, Castle KL, Borcherding WR 1982. T-cell cloning to detect the mutant 6-thioguanine-resistant lymphocytes present in human peripheral blood. PNAS 79:6617–21
   [Google Scholar]
4. 4.  Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S et al. 2013. Signatures of mutational processes in human cancer. Nature 500:415–21
   [Google Scholar]
5. 5.  Alioto TS, Buchhalter I, Derdak S, Hutter B, Eldridge MD et al. 2015. A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing. Nat. Commun. 6:10001
   [Google Scholar]
6. 6.  Alkan C, Coe BP, Eichler EE 2011. Genome structural variation discovery and genotyping. Nat. Rev. Genet. 12:363–76
   [Google Scholar]
7. 7.  Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM et al. (1000 Genomes Proj. Consort.). 2015. A global reference for human genetic variation. Nature 526:68–74
   [Google Scholar]
8. 8.  Bae T, Tomasini L, Mariani J, Zhou B, Roychowdhury T et al. 2018. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science 359:550–55
   [Google Scholar]
9. 9.  Baer CF, Miyamoto MM, Denver DR 2007. Mutation rate variation in multicellular eukaryotes: causes and consequences. Nat. Rev. Genet. 8:619–31
   [Google Scholar]
10. 10.  Beck CR, Garcia-Perez JL, Badge RM, Moran JV 2011. LINE-1 elements in structural variation and disease. Annu. Rev. Genom. Hum. Genet. 12:187–215
    [Google Scholar]
11. 11.  Behjati S, Huch M, van Boxtel R, Karthaus W, Wedge DC et al. 2014. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513:422–25
    [Google Scholar]
12. 12.  Biesecker LG, Spinner NB 2013. A genomic view of mosaicism and human disease. Nat. Rev. Genet. 14:307–20
    [Google Scholar]
13. 13.  Blokzijl F, de Ligt J, Jager M, Sasselli V, Roerink S et al. 2016. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 538:260–64
    [Google Scholar]
14. 14.  Bourc'his D, Bestor TH 2004. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431:96–99
    [Google Scholar]
15. 15.  Bruder CE, Piotrowski A, Gijsbers AA, Andersson R, Erickson S et al. 2008. Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am. J. Hum. Genet. 82:763–71
    [Google Scholar]
16. 16.  Cai X, Evrony GD, Lehmann HS, Elhosary PC, Mehta BK et al. 2014. Single-cell, genome-wide sequencing identifies clonal somatic copy-number variation in the human brain. Cell Rep 8:1280–89
    [Google Scholar]
17. 17.  Campbell CD, Eichler EE 2013. Properties and rates of germline mutations in humans. Trends Genet 29:575–84
    [Google Scholar]
18. 18.  Campbell PJ, Stephens PJ, Pleasance ED, O'Meara S, Li H et al. 2008. Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat. Genet. 40:722–29
    [Google Scholar]
19. 19.  Chen C, Xing D, Tan L, Li H, Zhou G et al. 2017. Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI). Science 356:189–94
    [Google Scholar]
20. 20.  Chiang C, Scott AJ, Davis JR, Tsang EK, Li X et al. 2017. The impact of structural variation on human gene expression. Nat. Genet. 49:692–99
    [Google Scholar]
21. 21.  Collins AR, Cadet J, Mőller L, Poulsen HE, Viña J 2004. Are we sure we know how to measure 8-oxo-7,8-dihydroguanine in DNA from human cells?. Arch. Biochem. Biophys. 423:57–65
    [Google Scholar]
22. 22.  Conrad DF, Keebler JE, DePristo MA, Lindsay SJ, Zhang Y et al. 2011. Variation in genome-wide mutation rates within and between human families. Nat. Genet. 43:712–14
    [Google Scholar]
23. 23.  Coolbaugh-Murphy MI, Xu J, Ramagli LS, Brown BW, Siciliano MJ 2005. Microsatellite instability (MSI) increases with age in normal somatic cells. Mech. Ageing Dev. 126:1051–59
    [Google Scholar]
24. 24.  de Duve C 2005. The onset of selection. Nature 433:581–82
    [Google Scholar]
25. 25.  de Grey AD 2007. Protagonistic pleiotropy: why cancer may be the only pathogenic effect of accumulating nuclear mutations and epimutations in aging. Mech. Ageing Dev. 128:456–59
    [Google Scholar]
26. 26.  Delhanty JDA, Griffin DK, Handyside AH, Harper J, Atkinson GHG et al. 1993. Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation, (FISH). Hum. Mol. Genet. 2:1183–85
    [Google Scholar]
27. 27.  Dewey FE, Murray MF, Overton JD, Habegger L, Leader JB et al. 2016. Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study. Science 354:aaf6814
    [Google Scholar]
28. 28.  Dollé MET, Giese H, Hopkins CL, Martus HJ, Hausdorff JM, Vijg J 1997. Rapid accumulation of genome rearrangements in liver but not in brain of old mice. Nat. Genet. 17:431–34
    [Google Scholar]
29. 29.  Dollé MET, Snyder WK, Dunson DB, Vijg J 2002. Mutational fingerprints of aging. Nucleic Acids Res 30:545–49
    [Google Scholar]
30. 30.  Dollé MET, Snyder WK, Gossen JA, Lohman PHM, Vijg J 2000. Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine. PNAS 97:8403–8
    [Google Scholar]
31. 31.  Dollé MET, Vijg J 2002. Genome dynamics in aging mice. Genome Res 12:1732–38
    [Google Scholar]
32. 32.  Dong X, Zhang L, Milholland B, Lee M, Maslov AY et al. 2017. Accurate identification of single-nucleotide variants in whole-genome-amplified single cells. Nat. Methods 14:491–93
    [Google Scholar]
33. 33.  Duncan AW 2013. Aneuploidy, polyploidy and ploidy reversal in the liver. Semin. Cell Dev. Biol. 24:347–56
    [Google Scholar]
34. 34.  Duncan AW, Hanlon Newell AE, Bi W, Finegold MJ, Olson SB et al. 2012. Aneuploidy as a mechanism for stress-induced liver adaptation. J. Clin. Investig. 122:3307–15
    [Google Scholar]
35. 35.  Duncan AW, Hanlon Newell AE, Smith L, Wilson EM, Olson SB et al. 2012. Frequent aneuploidy among normal human hepatocytes. Gastroenterology 142:25–28
    [Google Scholar]
36. 36.  Duncan AW, Taylor MH, Hickey RD, Hanlon Newell AE, Lenzi ML et al. 2010. The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature 467:707–10
    [Google Scholar]
37. 37.  Ellegren H 2004. Microsatellites: simple sequences with complex evolution. Nat. Rev. Genet. 5:435–45
    [Google Scholar]
38. 38.  Erickson RP 2010. Somatic gene mutation and human disease other than cancer: an update. Mutat. Res. 705:96–106
    [Google Scholar]
39. 39.  Erwin JA, Paquola ACM, Singer T, Gallina I, Novotny M et al. 2016. L1-associated genomic regions are deleted in somatic cells of the healthy human brain. Nat. Neurosci. 19:1583–91
    [Google Scholar]
40. 40.  Evans HJ 1988. Mutation as a cause of genetic disease. Philos. Trans. R. Soc. B 319:325–40
    [Google Scholar]
41. 41.  Evrony GD, Cai X, Lee E, Hills LB, Elhosary PC et al. 2012. Single-neuron sequencing analysis of L1 retrotransposition and somatic mutation in the human brain. Cell 151:483–96
    [Google Scholar]
42. 42.  Evrony GD, Lee E, Park PJ, Walsh CA 2016. Resolving rates of mutation in the brain using single-neuron genomics. eLife 5:e12966
    [Google Scholar]
43. 43.  Ewing AD, Ballinger TJ, Earl D, Harris CC, Ding L et al. 2013. Retrotransposition of gene transcripts leads to structural variation in mammalian genomes. Genome Biol 14:R22
    [Google Scholar]
44. 44.  Faggioli F, Vijg J, Montagna C 2011. Chromosomal aneuploidy in the aging brain. Mech. Ageing Dev. 132:429–36
    [Google Scholar]
45. 45.  Faggioli F, Vijg J, Montagna C 2014. Four-color FISH for the detection of low-level aneuploidy in interphase cells. Methods Mol. Biol. 1136:291–305
    [Google Scholar]
46. 46.  Faggioli F, Wang T, Vijg J, Montagna C 2012. Chromosome-specific accumulation of aneuploidy in the aging mouse brain. Hum. Mol. Genet. 21:5246–53
    [Google Scholar]
47. 47.  Failla G 1958. The aging process and cancerogenesis. Ann. N.Y. Acad. Sci. 71:1124–40
    [Google Scholar]
48. 48.  Ferguson-Smith MA 2015. History and evolution of cytogenetics. Mol. Cytogenet. 8:19
    [Google Scholar]
49. 49.  Feuk L, Carson AR, Scherer SW 2006. Structural variation in the human genome. Nat. Rev. Genet. 7:85–97
    [Google Scholar]
50. 50.  Fiegler H, Geigl JB, Langer S, Rigler D, Porter K et al. 2007. High resolution array-CGH analysis of single cells. Nucleic Acids Res 35:e15
    [Google Scholar]
51. 51.  Fiorentino F, Biricik A, Bono S, Spizzichino L, Cotroneo E et al. 2014. Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil. Steril. 101:1375–82
    [Google Scholar]
52. 52.  Forsberg LA, Rasi C, Razzaghian HR, Pakalapati G, Waite L et al. 2012. Age-related somatic structural changes in the nuclear genome of human blood cells. Am. J. Hum. Genet. 90:217–28
    [Google Scholar]
53. 53.  Franco I, Johansson A, Olsson K, Vrtačnik P, Lundin P et al. 2018. Somatic mutagenesis in satellite cells associates with human skeletal muscle aging. Nat. Commun. 9:800
    [Google Scholar]
54. 54.  Goodier JL 2014. Retrotransposition in tumors and brains. Mobile DNA 5:11
    [Google Scholar]
55. 55.  Goodier JL 2016. Restricting retrotransposons: a review. Mobile DNA 7:16
    [Google Scholar]
56. 56.  Goodier JL, Kazazian HH Jr. 2008. Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell 135:23–35
    [Google Scholar]
57. 57.  Gossen JA, de Leeuw WJ, Tan CH, Zwarthoff EC, Berends F et al. 1989. Efficient rescue of integrated shuttle vectors from transgenic mice: a model for studying mutations in vivo. PNAS 86:7971–75
    [Google Scholar]
58. 58.  Gundry M, Vijg J 2012. Direct mutation analysis by high-throughput sequencing: from germline to low-abundant, somatic variants. Mutat. Res. 729:1–15
    [Google Scholar]
59. 59.  Hancks DC, Kazazian HH Jr. 2012. Active human retrotransposons: variation and disease. Curr. Opin. Genet. Dev. 22:191–203
    [Google Scholar]
60. 60.  Hoeijmakers JH 2001. Genome maintenance mechanisms for preventing cancer. Nature 411:366–74
    [Google Scholar]
61. 61.  Inaki K, Liu ET 2012. Structural mutations in cancer: mechanistic and functional insights. Trends Genet 28:550–59
    [Google Scholar]
62. 62.  Jacobs KB, Yeager M, Zhou W, Wacholder S, Wang Z et al. 2012. Detectable clonal mosaicism and its relationship to aging and cancer. Nat. Genet. 44:651–58
    [Google Scholar]
63. 63.  Jeffreys AJ, Neumann R, Wilson V 1990. Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis. Cell 60:473–85
    [Google Scholar]
64. 64.  Kano H, Godoy I, Courtney C, Vetter MR, Gerton GL et al. 2009. L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism. Genes Dev 23:1303–12
    [Google Scholar]
65. 65.  Keightley PD 2012. Rates and fitness consequences of new mutations in humans. Genetics 190:295–304
    [Google Scholar]
66. 66.  Kimura M 1960. Optimum mutation rate and degree of dominance as determined by the principle of minimum genetic load. J. Genet. 57:21–34
    [Google Scholar]
67. 67.  Kirkwood TB 1977. Evolution of ageing. Nature 270:301–4
    [Google Scholar]
68. 68.  Kirkwood TB 2005. Understanding the odd science of aging. Cell 120:437–47
    [Google Scholar]
69. 69.  Klawitter S, Fuchs NV, Upton KR, Munoz-Lopez M, Shukla R et al. 2016. Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells. Nat. Commun. 7:10286
    [Google Scholar]
70. 70.  Knouse KA, Wu J, Amon A 2016. Assessment of megabase-scale somatic copy number variation using single-cell sequencing. Genome Res 26:376–84
    [Google Scholar]
71. 71.  Knouse KA, Wu J, Whittaker CA, Amon A 2014. Single cell sequencing reveals low levels of aneuploidy across mammalian tissues. PNAS 111:13409–14
    [Google Scholar]
72. 72.  Kondrashov A 2012. Genetics: the rate of human mutation. Nature 488:467–68
    [Google Scholar]
73. 73.  Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P et al. 2012. Rate of de novo mutations and the importance of father's age to disease risk. Nature 488:471–75
    [Google Scholar]
74. 74.  Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC et al. 2001. Initial sequencing and analysis of the human genome. Nature 409:860–921
    [Google Scholar]
75. 75.  Lasken RS, Stockwell TB 2007. Mechanism of chimera formation during the Multiple Displacement Amplification reaction. BMC Biotechnol 7:19
    [Google Scholar]
76. 76.  Laurie CC, Laurie CA, Rice K, Doheny KF, Zelnick LR et al. 2012. Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nat. Genet. 44:642–50
    [Google Scholar]
77. 77.  Lee E, Iskow R, Yang L, Gokcumen O, Haseley P et al. 2012. Landscape of somatic retrotransposition in human cancers. Science 337:967–71
    [Google Scholar]
78. 78.  Lindahl T 1993. Instability and decay of the primary structure of DNA. Nature 362:709–15
    [Google Scholar]
79. 79.  Liyanage M, Coleman A, du Manoir S, Veldman T, McCormack S et al. 1996. Multicolour spectral karyotyping of mouse chromosomes. Nat. Genet. 14:312–15
    [Google Scholar]
80. 80.  Lodato MA, Rodin RE, Barton AR, Bohrson CL, Chittenden TW et al. 2018. Aging and neurodegeneration are associated with increased mutations in single human neurons. Science 359:555–59
    [Google Scholar]
81. 81.  Long AS, Lemieux CL, Arlt VM, White PA 2016. Tissue-specific in vivo genetic toxicity of nine polycyclic aromatic hydrocarbons assessed using the MutaMouse transgenic rodent assay. Toxicol. Appl. Pharmacol. 290:31–42
    [Google Scholar]
82. 82.  Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G 2013. The hallmarks of aging. Cell 153:1194–217
    [Google Scholar]
83. 83.  Lynch M, Ackerman MS, Gout JF, Long H, Sung W et al. 2016. Genetic drift, selection and the evolution of the mutation rate. Nat. Rev. Genet. 17:704–14
    [Google Scholar]
84. 84.  Machiela MJ, Zhou W, Karlins E, Sampson JN, Freedman ND et al. 2016. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nat. Commun. 7:11843
    [Google Scholar]
85. 85.  Martincorena I, Campbell PJ 2015. Somatic mutation in cancer and normal cells. Science 349:1483–89
    [Google Scholar]
86. 86.  Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P et al. 2015. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348:880–86
    [Google Scholar]
87. 87.  Maruvka YE, Mouw KW, Karlic R, Parasuraman P, Kamburov A et al. 2017. Analysis of somatic microsatellite indels identifies driver events in human tumors. Nat. Biotechnol. 35:951–59
    [Google Scholar]
88. 88.  Maslov AY, Quispe-Tintaya W, Gorbacheva T, White RR, Vijg J 2015. High-throughput sequencing in mutation detection: a new generation of genotoxicity tests?. Mutat. Res. 776:136–43
    [Google Scholar]
89. 89.  Maynard Smith J 1959. A theory of ageing. Nature 184:956–57
    [Google Scholar]
90. 90.  McConnell MJ, Lindberg MR, Brennand KJ, Piper JC, Voet T et al. 2013. Mosaic copy number variation in human neurons. Science 342:632–37
    [Google Scholar]
91. 91.  Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J et al. 1992. Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res 52:643–45
    [Google Scholar]
92. 92.  Milholland B, Auton A, Suh Y, Vijg J 2015. Age-related somatic mutations in the cancer genome. Oncotarget 6:24627–35
    [Google Scholar]
93. 93.  Milholland B, Dong X, Zhang L, Hao X, Suh Y, Vijg J 2017. Differences between germline and somatic mutation rates in humans and mice. Nat. Commun. 8:15183
    [Google Scholar]
94. 94.  Mitelman F, Johansson B, Mertens F 2004. Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Nat. Genet. 36:331–34
    [Google Scholar]
95. 95.  Mitelman F, Johansson B, Mertens F 2007. The impact of translocations and gene fusions on cancer causation. Nat. Rev. Cancer 7:233–45
    [Google Scholar]
96. 96.  Moncunill V, Gonzalez S, Bea S, Andrieux LO, Salaverria I et al. 2014. Comprehensive characterization of complex structural variations in cancer by directly comparing genome sequence reads. Nat. Biotechnol. 32:1106–12
    [Google Scholar]
97. 97.  Mosch B, Morawski M, Mittag A, Lenz D, Tarnok A, Arendt T 2007. Aneuploidy and DNA replication in the normal human brain and Alzheimer's disease. J. Neurosci. 27:6859–67
    [Google Scholar]
98. 98.  Negrini S, Gorgoulis VG, Halazonetis TD 2010. Genomic instability—an evolving hallmark of cancer. Nat. Rev. Mol. Cell Biol. 11:220–28
    [Google Scholar]
99. 99.  Nowell PC 1976. The clonal evolution of tumor cell populations. Science 194:23–28
    [Google Scholar]
100. 100.  Ono T, Ikehata H, Nakamura S, Saito Y, Hosoi Y et al. 2000. Age-associated increase of spontaneous mutant frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse. Mutat. Res. 447:165–77
     [Google Scholar]
101. 101.  Osgood EE 1957. A unifying concept of the etiology of the leukemias, lymphomas, and cancers. J. Natl. Cancer Inst. 18:155–66
     [Google Scholar]
102. 102.  Parsons R, Li GM, Longley M, Modrich P, Liu B et al. 1995. Mismatch repair deficiency in phenotypically normal human cells. Science 268:738–40
     [Google Scholar]
103. 103.  Pinkel D, Straume T, Gray JW 1986. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. PNAS 83:2934–38
     [Google Scholar]
104. 104.  Poduri A, Evrony GD, Cai X, Walsh CA 2013. Somatic mutation, genomic variation, and neurological disease. Science 341:1237758
     [Google Scholar]
105. 105.  Quispe-Tintaya W, Gorbacheva T, Lee M, Makhortov S, Popov VN et al. 2016. Quantitative detection of low-abundance somatic structural variants in normal cells by high-throughput sequencing. Nat. Methods 13:584–86
     [Google Scholar]
106. 106.  Ramsey MJ, Moore DH2nd, Briner JF, Lee DA, Olsen L et al. 1995. The effects of age and lifestyle factors on the accumulation of cytogenetic damage as measured by chromosome painting. Mutat. Res. 338:95–106
     [Google Scholar]
107. 107.  Rehen SK, McConnell MJ, Kaushal D, Kingsbury MA, Yang AH, Chun J 2001. Chromosomal variation in neurons of the developing and adult mammalian nervous system. PNAS 98:13361–66
     [Google Scholar]
108. 108.  Rehen SK, Yung YC, McCreight MP, Kaushal D, Yang AH et al. 2005. Constitutional aneuploidy in the normal human brain. J. Neurosci. 25:2176–80
     [Google Scholar]
109. 109.  Rouhani FJ, Nik-Zainal S, Wuster A, Li Y, Conte N et al. 2016. Mutational history of a human cell lineage from somatic to induced pluripotent stem cells. PLOS Genet 12:e1005932
     [Google Scholar]
110. 110.  Schrock E, du Manoir S, Veldman T, Schoell B, Wienberg J et al. 1996. Multicolor spectral karyotyping of human chromosomes. Science 273:494–97
     [Google Scholar]
111. 111.  Schukken KM, Foijer F 2018. CIN and aneuploidy: different concepts, different consequences. Bioessays 40:1700147
     [Google Scholar]
112. 112.  Seberg O, Petersen G 2009. A unified classification system for eukaryotic transposable elements should reflect their phylogeny. Nat. Rev. Genet. 10:276
     [Google Scholar]
113. 113.  Shao C, Deng L, Henegariu O, Liang L, Raikwar N et al. 1999. Mitotic recombination produces the majority of recessive fibroblast variants in heterozygous mice. PNAS 96:9230–35
     [Google Scholar]
114. 114.  Stephens PJ, McBride DJ, Lin ML, Varela I, Pleasance ED et al. 2009. Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature 462:1005–10
     [Google Scholar]
115. 115.  Stuart GR, Oda Y, de Boer JG, Glickman BW 2000. Mutation frequency and specificity with age in liver, bladder and brain of lacI transgenic mice. Genetics 154:1291–300
     [Google Scholar]
116. 116.  Sturtevant AH 1937. Essays on evolution. I. On the effects of selection on mutation rate. Quart. Rev. Biol. 12:464–76
     [Google Scholar]
117. 117.  Szilard L 1959. On the nature of the aging process. PNAS 45:30–45
     [Google Scholar]
118. 118.  Thomas P, Fenech M 2008. Chromosome 17 and 21 aneuploidy in buccal cells is increased with ageing and in Alzheimer's disease. Mutagenesis 23:57–65
     [Google Scholar]
119. 119.  Treff NR, Su J, Tao X, Northrop LE, Scott RT Jr. 2011. Single-cell whole-genome amplification technique impacts the accuracy of SNP microarray-based genotyping and copy number analyses. Mol. Hum. Reprod. 17:335–43
     [Google Scholar]
120. 120.  Upton KR, Gerhardt DJ, Jesuadian JS, Richardson SR, Sanchez-Luque FJ et al. 2015. Ubiquitous L1 mosaicism in hippocampal neurons. Cell 161:228–39
     [Google Scholar]
121. 121.  van den Bos H, Spierings DCJ, Taudt AS, Bakker B, Porubský D et al. 2016. Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer's disease neurons. Genome Biol 17:116
     [Google Scholar]
122. 122.  Van Loo P, Voet T 2014. Single cell analysis of cancer genomes. Curr. Opin. Genet. Dev. 24:82–91
     [Google Scholar]
123. 123.  Vanneste E, Van der Aa N, Voet T, Vermeesch JR 2012. Aneuploidy and copy number variation in early human development. Semin. Reprod. Med. 30:302–8
     [Google Scholar]
124. 124.  Vanneste E, Voet T, Le Caignec C, Ampe M, Konings P et al. 2009. Chromosome instability is common in human cleavage-stage embryos. Nat. Med. 15:577–83
     [Google Scholar]
125. 125.  Vijg J 2007. Aging of the Genome Oxford, UK: Oxford Univ. Press
126. 126.  Vijg J, van Steeg H 1998. Transgenic assays for mutations and cancer: current status and future perspectives. Mutat. Res. 400:337–54
     [Google Scholar]
127. 127.  Voet T, Vanneste E, Vermeesch JR 2011. The human cleavage stage embryo is a cradle of chromosomal rearrangements. Cytogenet. Genome Res. 133:160–68
     [Google Scholar]
128. 128.  Wahnschaffe U, Bitsch A, Kielhorn J, Mangelsdorf I 2005. Mutagenicity testing with transgenic mice. Part II: Comparison with the mouse spot test. J. Carcinog. 4:4
     [Google Scholar]
129. 129.  Wang J, Fan HC, Behr B, Quake SR 2012. Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell 150:402–12
     [Google Scholar]
130. 130.  Watson J, Crick F 1953. Molecular structure of nucleic acids. Nature 171:737–38
     [Google Scholar]
131. 131.  Weismann A 1893. The Germ-Plasm: A Theory of Heredity London: Walter Scott
132. 132.  Wells D, Delhanty JDA 2000. Comprehensive chromosomal analysis of human preimplantation embryos using whole genome amplification and single cell comparative genomic hybridization. Mol. Hum. Reprod. 6:1055–62
     [Google Scholar]
133. 133.  Wunderlich V 2007. Early references to the mutational origin of cancer. Int. J. Epidemiol. 36:246–47
     [Google Scholar]
134. 134.  Yang L, Luquette LJ, Gehlenborg N, Xi R, Haseley PS et al. 2013. Diverse mechanisms of somatic structural variations in human cancer genomes. Cell 153:919–29
     [Google Scholar]
135. 135.  Yang Y, Geldmacher DS, Herrup K 2001. DNA replication precedes neuronal cell death in Alzheimer's disease. J. Neurosci. 21:2661–68
     [Google Scholar]
136. 136.  Yurov YB, Iourov IY, Vorsanova SG, Liehr T, Kolotii AD et al. 2007. Aneuploidy and confined chromosomal mosaicism in the developing human brain. PLOS ONE 2:e558
     [Google Scholar]
137. 137.  Zhang ZD, Du J, Lam H, Abyzov A, Urban AE et al. 2011. Identification of genomic indels and structural variations using split reads. BMC Genom 12:375
     [Google Scholar]
138. 138.  Zong C, Lu S, Chapman AR, Xie XS 2012. Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 338:1622–26
     [Google Scholar]