1932

Abstract

Mosaicism refers to the occurrence of two or more genomes in an individual derived from a single zygote. Germline mosaicism is a mutation that is limited to the gonads and can be transmitted to offspring. Somatic mosaicism is a postzygotic mutation that occurs in the soma, and it may occur at any developmental stage or in adult tissues. Mosaic variation may be classified in six ways: () germline or somatic origin, () class of DNA mutation (ranging in scale from single base pairs to multiple chromosomes), () developmental context, () body location(s), () functional consequence (including deleterious, neutral, or advantageous), and () additional sources of mosaicism, including mitochondrial heteroplasmy, exogenous DNA sources such as vectors, and epigenetic changes such as imprinting and X-chromosome inactivation. Technological advances, including single-cell and other next-generation sequencing, have facilitated improved sensitivity and specificity to detect mosaicism in a variety of biological contexts.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-041720-093403
2020-11-23
2024-12-01
Loading full text...

Full text loading...

/deliver/fulltext/genet/54/1/annurev-genet-041720-093403.html?itemId=/content/journals/10.1146/annurev-genet-041720-093403&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Ajay SS, Parker SC, Abaan HO, Fajardo KV, Margulies EH 2011. Accurate and comprehensive sequencing of personal genomes. Genome Res 21:1498–505
    [Google Scholar]
  2. 2. 
    Alexandrov LB, Kim J, Haradhvala NJ, Huang MN, Ng AWT et al. 2020. The repertoire of mutational signatures in human cancer. Nature 578:94–101
    [Google Scholar]
  3. 3. 
    Antonarakis SE. 2017. Down syndrome and the complexity of genome dosage imbalance. Nat. Rev. Genet. 18:147–63
    [Google Scholar]
  4. 4. 
    Ardui S, Ameur A, Vermeesch JR, Hestand MS 2018. Single molecule real-time (SMRT) sequencing comes of age: applications and utilities for medical diagnostics. Nucleic Acids Res 46:2159–68
    [Google Scholar]
  5. 5. 
    Arvey A, Hermann A, Hsia CC, Ie E, Freund Y, McGinnis W 2010. Minimizing off-target signals in RNA fluorescent in situ hybridization. Nucleic Acids Res 38:e115
    [Google Scholar]
  6. 6. 
    Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM et al. 2015. A global reference for human genetic variation. Nature 526:68–74
    [Google Scholar]
  7. 7. 
    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]
  8. 8. 
    Bakker E, Van Broeckhoven C, Bonten EJ, van de Vooren MJ, Veenema H et al. 1987. Germline mosaicism and Duchenne muscular dystrophy mutations. Nature 329:554–56
    [Google Scholar]
  9. 9. 
    Bassing CH, Swat W, Alt FW 2002. The mechanism and regulation of chromosomal V(D)J recombination. Cell 109:Suppl.S45–55
    [Google Scholar]
  10. 10. 
    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]
  11. 11. 
    Bunnell ME, Wilkins-Haug L, Reiss R 2017. Should embryos with autosomal monosomy by preimplantation genetic testing for aneuploidy be transferred?: Implications for embryo selection from a systematic literature review of autosomal monosomy survivors. Prenat. Diagn. 37:1273–80
    [Google Scholar]
  12. 12. 
    Bushman DM, Chun J. 2013. The genomically mosaic brain: aneuploidy and more in neural diversity and disease. Semin. Cell Dev. Biol. 24:357–69
    [Google Scholar]
  13. 13. 
    Butler MG. 2009. Genomic imprinting disorders in humans: a mini-review. J. Assist. Reprod. Genet. 26:477–86
    [Google Scholar]
  14. 14. 
    Campbell IM, Shaw CA, Stankiewicz P, Lupski JR 2015. Somatic mosaicism: implications for disease and transmission genetics. Trends Genet 31:382–92
    [Google Scholar]
  15. 15. 
    Carneiro MO, Russ C, Ross MG, Gabriel SB, Nusbaum C, DePristo MA 2012. Pacific biosciences sequencing technology for genotyping and variation discovery in human data. BMC Genom 13:375
    [Google Scholar]
  16. 16. 
    Carvalho CM, Lupski JR. 2016. Mechanisms underlying structural variant formation in genomic disorders. Nat. Rev. Genet. 17:224–38
    [Google Scholar]
  17. 17. 
    Chaisson MJ, Huddleston J, Dennis MY, Sudmant PH, Malig M et al. 2015. Resolving the complexity of the human genome using single-molecule sequencing. Nature 517:608–11
    [Google Scholar]
  18. 18. 
    Cho S, Maharathi B, Ball KL, Loeb JA, Pevsner J 2019. Sturge-Weber syndrome patient registry: delayed diagnosis and poor seizure control. J. Pediatr. 215:158–63.e6
    [Google Scholar]
  19. 19. 
    Clarke CM, Edwards JH. 1961. 21-Trisomy/normal mosaicism in an intelligent child with some Mongoloid characters. Lancet 1:1028–30
    [Google Scholar]
  20. 20. 
    Clarke J, Wu HC, Jayasinghe L, Patel A, Reid S, Bayley H 2009. Continuous base identification for single-molecule nanopore DNA sequencing. Nat. Nanotechnol. 4:265–70
    [Google Scholar]
  21. 21. 
    Colella P, Ronzitti G, Mingozzi F 2018. Emerging issues in AAV-mediated in vivo gene therapy. Mol. Ther. Methods Clin. Dev. 8:87–104
    [Google Scholar]
  22. 22. 
    Conlin LK, Kaur M, Izumi K, Campbell L, Wilkens A et al. 2012. Utility of SNP arrays in detecting, quantifying, and determining meiotic origin of tetrasomy 12p in blood from individuals with Pallister-Killian syndrome. Am. J. Med. Genet. A 158A:3046–53
    [Google Scholar]
  23. 23. 
    Copeland WC. 2010. The mitochondrial DNA polymerase in health and disease. Subcell. Biochem. 50:211–22
    [Google Scholar]
  24. 24. 
    De S. 2011. Somatic mosaicism in healthy human tissues. Trends Genet 27:217–23
    [Google Scholar]
  25. 25. 
    de Koning AP, Gu W, Castoe TA, Batzer MA, Pollock DD 2011. Repetitive elements may comprise over two-thirds of the human genome. PLOS Genet 7:e1002384
    [Google Scholar]
  26. 26. 
    Delhanty JD. 2011. Inherited aneuploidy: germline mosaicism. Cytogenet. Genome Res. 133:136–40
    [Google Scholar]
  27. 27. 
    Delhanty JD, SenGupta SB, Ghevaria H 2019. How common is germinal mosaicism that leads to premeiotic aneuploidy in the female. ? J. Assisted Reprod. Genet. 36:2403–18
    [Google Scholar]
  28. 28. 
    D'Gama AM, Walsh CA. 2018. Somatic mosaicism and neurodevelopmental disease. Nat. Neurosci. 21:1504–14
    [Google Scholar]
  29. 29. 
    Dorner T, Lipsky PE. 2001. Immunoglobulin variable-region gene usage in systemic autoimmune diseases. Arthritis Rheum 44:2715–27
    [Google Scholar]
  30. 30. 
    Dou Y, Gold HD, Luquette LJ, Park PJ 2018. Detecting somatic mutations in normal cells. Trends Genet 34:545–57
    [Google Scholar]
  31. 31. 
    Dou Y, Yang X, Li Z, Wang S, Zhang Z et al. 2017. Postzygotic single-nucleotide mosaicisms contribute to the etiology of autism spectrum disorder and autistic traits and the origin of mutations. Hum. Mutat. 38:1002–13
    [Google Scholar]
  32. 32. 
    Dumanski JP, Piotrowski A. 2012. Structural genetic variation in the context of somatic mosaicism. Methods Mol. Biol. 838:249–72
    [Google Scholar]
  33. 33. 
    Durham SE, Samuels DC, Cree LM, Chinnery PF 2007. Normal levels of wild-type mitochondrial DNA maintain cytochrome c oxidase activity for two pathogenic mitochondrial DNA mutations but not for m.3243A→G. Am. J. Hum. Genet. 81:189–95
    [Google Scholar]
  34. 34. 
    Eid J, Fehr A, Gray J, Luong K, Lyle J et al. 2009. Real-time DNA sequencing from single polymerase molecules. Science 323:133–38
    [Google Scholar]
  35. 35. 
    Elliott HR, Samuels DC, Eden JA, Relton CL, Chinnery PF 2008. Pathogenic mitochondrial DNA mutations are common in the general population. Am. J. Hum. Genet. 83:254–60
    [Google Scholar]
  36. 36. 
    Engel E. 1980. A new genetic concept: uniparental disomy and its potential effect, isodisomy. Am. J. Med. Genet. 6:137–43
    [Google Scholar]
  37. 37. 
    Engel E. 1997. Uniparental disomy (UPD). Genomic imprinting and a case for new genetics (prenatal and clinical implications: the “Likon” concept). Ann. Genet. 40:24–34
    [Google Scholar]
  38. 38. 
    Erwin JA, Marchetto MC, Gage FH 2014. Mobile DNA elements in the generation of diversity and complexity in the brain. Nat. Rev. Neurosci. 15:497–506
    [Google Scholar]
  39. 39. 
    Eur. Chromosom. 16 Tuberous Scler. Consort 1993. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75:1305–15
    [Google Scholar]
  40. 40. 
    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]
  41. 41. 
    Ferreira V, Petry H, Salmon F 2014. Immune responses to AAV-vectors, the Glybera example from bench to bedside. Front. Immunol. 5:82
    [Google Scholar]
  42. 42. 
    Fitzgerald PH, Lycette RR. 1961. Mosaicism in man, involving the autosome associated with mongolism. Heredity 16:509–12
    [Google Scholar]
  43. 43. 
    Forsberg LA, Gisselsson D, Dumanski JP 2017. Mosaicism in health and disease—clones picking up speed. Nat. Rev. Genet. 18:128–42
    [Google Scholar]
  44. 44. 
    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]
  45. 45. 
    Freed D, Pevsner J. 2016. The contribution of mosaic variants to autism spectrum disorder. PLOS Genet 12:e1006245
    [Google Scholar]
  46. 46. 
    Gajecka M. 2016. Unrevealed mosaicism in the next-generation sequencing era. Mol. Genet. Genom. 291:513–30
    [Google Scholar]
  47. 47. 
    Garcia-Linares C, Fernandez-Rodriguez J, Terribas E, Mercade J, Pros E et al. 2011. Dissecting loss of heterozygosity (LOH) in neurofibromatosis type 1-associated neurofibromas: importance of copy neutral LOH. Hum. Mutat. 32:78–90
    [Google Scholar]
  48. 48. 
    Garcia-Romero MT, Parkin P, Lara-Corrales I 2016. Mosaic neurofibromatosis type 1: a systematic review. Pediatr. Dermatol. 33:9–17
    [Google Scholar]
  49. 49. 
    Gudmundsson S, Wilbe M, Ekvall S, Ameur A, Cahill N et al. 2017. Revertant mosaicism repairs skin lesions in a patient with keratitis-ichthyosis-deafness syndrome by second-site mutations in connexin 26. Hum. Mol. Genet. 26:1070–77
    [Google Scholar]
  50. 50. 
    Happle R. 1987. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J. Am. Acad. Dermatol. 16:899–906
    [Google Scholar]
  51. 51. 
    Hassold T, Chen N, Funkhouser J, Jooss T, Manuel B et al. 1980. A cytogenetic study of 1000 spontaneous abortions. Ann. Hum. Genet. 44:151–78
    [Google Scholar]
  52. 52. 
    Henikoff S, Shilatifard A. 2011. Histone modification: cause or cog. ? Trends Genet 27:389–96
    [Google Scholar]
  53. 53. 
    Hirschhorn R. 2003. In vivo reversion to normal of inherited mutations in humans. J. Med. Genet. 40:721–28
    [Google Scholar]
  54. 54. 
    Iourov IY, Vorsanova SG, Yurov YB, Kutsev SI 2019. Ontogenetic and pathogenetic views on somatic chromosomal mosaicism. Genes 10:379
    [Google Scholar]
  55. 55. 
    Issa JP. 2014. Aging and epigenetic drift: a vicious cycle. J. Clin. Invest. 124:24–29
    [Google Scholar]
  56. 56. 
    Jackson-Cook C. 2011. Constitutional and acquired autosomal aneuploidy. Clin. Lab. Med. 31:481–511
    [Google Scholar]
  57. 57. 
    Jonsson H, Sulem P, Arnadottir GA, Palsson G, Eggertsson HP et al. 2018. Multiple transmissions of de novo mutations in families. Nat. Genet. 50:1674–80
    [Google Scholar]
  58. 58. 
    Jonsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F et al. 2017. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature 549:519–22
    [Google Scholar]
  59. 59. 
    Kalousek DK. 1994. Confined placental mosaicism and uniparental disomy. Funct. Dev. Morphol. 4:93–98
    [Google Scholar]
  60. 60. 
    Kalousek DK, Vekemans M. 1996. Confined placental mosaicism. J. Med. Genet. 33:529–33
    [Google Scholar]
  61. 61. 
    Kazazian HH Jr, Moran JV. 2017. Mobile DNA in health and disease. N. Engl. J. Med. 377:361–70
    [Google Scholar]
  62. 62. 
    King DA, Jones WD, Crow YJ, Dominiczak AF, Foster NA et al. 2015. Mosaic structural variation in children with developmental disorders. Hum. Mol. Genet. 24:2733–45
    [Google Scholar]
  63. 63. 
    Knudson AG Jr 1971. Mutation and cancer: statistical study of retinoblastoma. PNAS 68:820–23
    [Google Scholar]
  64. 64. 
    Koche RP, Rodriguez-Fos E, Helmsauer K, Burkert M, MacArthur IC et al. 2020. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma. Nat. Genet. 52:29–34
    [Google Scholar]
  65. 65. 
    Kotzot D. 1999. Abnormal phenotypes in uniparental disomy (UPD): fundamental aspects and a critical review with bibliography of UPD other than 15. Am. J. Med. Genet. 82:265–74
    [Google Scholar]
  66. 66. 
    Krupp DR, Barnard RA, Duffourd Y, Evans SA, Mulqueen RM et al. 2017. Exonic mosaic mutations contribute risk for autism spectrum disorder. Am. J. Hum. Genet. 101:369–90
    [Google Scholar]
  67. 67. 
    Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K et al. 2005. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309:481–84
    [Google Scholar]
  68. 68. 
    Lai-Cheong JE, McGrath JA, Uitto J 2011. Revertant mosaicism in skin: natural gene therapy. Trends Mol. Med. 17:140–48
    [Google Scholar]
  69. 69. 
    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]
  70. 70. 
    Lejeune J, Gautier M, Turpin R 1959. Étude des chromosomes somatiques de neuf enfants mongoliens. C. R. Acad. Sci. Paris 248:1721–22
    [Google Scholar]
  71. 71. 
    Lemmers RJ, van der Vliet PJ, Klooster R, Sacconi S, Camano P et al. 2010. A unifying genetic model for facioscapulohumeral muscular dystrophy. Science 329:1650–53
    [Google Scholar]
  72. 72. 
    Lemmers RJ, van der Wielen MJ, Bakker E, Padberg GW, Frants RR, van der Maarel SM 2004. Somatic mosaicism in FSHD often goes undetected. Ann. Neurol. 55:845–50
    [Google Scholar]
  73. 73. 
    Levy B, Burnside RD. 2019. Are all chromosome microarrays the same? What clinicians need to know. Prenat. Diagn. 39:157–64
    [Google Scholar]
  74. 74. 
    Li W, Yang L, Harris RS, Lin L, Olson TL et al. 2019. Retrovirus insertion site analysis of LGL leukemia patient genomes. BMC Med. Genom. 12:88
    [Google Scholar]
  75. 75. 
    Lim ET, Uddin M, De Rubeis S, Chan Y, Kamumbu AS et al. 2017. Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Nat. Neurosci. 20:1217–24
    [Google Scholar]
  76. 76. 
    Lim YH, Moscato Z, Choate KA 2017. Mosaicism in cutaneous disorders. Annu. Rev. Genet. 51:123–41
    [Google Scholar]
  77. 77. 
    Lodato MA, Walsh CA. 2019. Genome aging: Somatic mutation in the brain links age-related decline with disease and nominates pathogenic mechanisms. Hum. Mol. Genet. 28:R197–206
    [Google Scholar]
  78. 78. 
    Loftfield E, Zhou W, Graubard BI, Yeager M, Chanock SJ et al. 2018. Predictors of mosaic chromosome Y loss and associations with mortality in the UK Biobank. Sci. Rep. 8:12316
    [Google Scholar]
  79. 79. 
    Lynch M. 2010. Rate, molecular spectrum, and consequences of human mutation. PNAS 107:961–68
    [Google Scholar]
  80. 80. 
    Machiela MJ. 2019. Mosaicism, aging and cancer. Curr. Opin. Oncol. 31:108–13
    [Google Scholar]
  81. 81. 
    Machiela MJ, Zhou W, Sampson JN, Dean MC, Jacobs KB et al. 2015. Characterization of large structural genetic mosaicism in human autosomes. Am. J. Hum. Genet. 96:487–97
    [Google Scholar]
  82. 82. 
    Maeda N, Fan H, Yoshikai Y 2008. Oncogenesis by retroviruses: old and new paradigms. Rev. Med. Virol. 18:387–405
    [Google Scholar]
  83. 83. 
    Mak KY, Rajapaksha IG, Angus PW, Herath CB 2017. The adeno-associated virus—a safe and promising vehicle for liver-specific gene therapy of inherited and non-inherited disorders. Curr. Gene Ther. 17:4–16
    [Google Scholar]
  84. 84. 
    McConnell MJ, Moran JV, Abyzov A, Akbarian S, Bae T et al. 2017. Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science 356:eaal1641
    [Google Scholar]
  85. 85. 
    McCoy RC. 2017. Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm. Trends Genet 33:448–63
    [Google Scholar]
  86. 86. 
    McKenna A, Gagnon JA. 2019. Recording development with single cell dynamic lineage tracing. Development 146:dev169730
    [Google Scholar]
  87. 87. 
    Meynert AM, Ansari M, FitzPatrick DR, Taylor MS 2014. Variant detection sensitivity and biases in whole genome and exome sequencing. BMC Bioinform 15:247
    [Google Scholar]
  88. 88. 
    Migeon BR. 1998. Non-random X chromosome inactivation in mammalian cells. Cytogenet. Cell Genet. 80:142–48
    [Google Scholar]
  89. 89. 
    Migeon BR. 2006. The role of X inactivation and cellular mosaicism in women's health and sex-specific diseases. JAMA 295:1428–33
    [Google Scholar]
  90. 90. 
    Moller HD, Mohiyuddin M, Prada-Luengo I, Sailani MR, Halling JF et al. 2018. Circular DNA elements of chromosomal origin are common in healthy human somatic tissue. Nat. Commun. 9:1069
    [Google Scholar]
  91. 91. 
    Monk D, Mackay DJG, Eggermann T, Maher ER, Riccio A 2019. Genomic imprinting disorders: lessons on how genome, epigenome and environment interact. Nat. Rev. Genet. 20:235–48
    [Google Scholar]
  92. 92. 
    Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J et al. 2011. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N. Engl. J. Med. 365:2357–65
    [Google Scholar]
  93. 93. 
    Niemitz EL, Feinberg AP. 2004. Epigenetics and assisted reproductive technology: a call for investigation. Am. J. Hum. Genet. 74:599–609
    [Google Scholar]
  94. 94. 
    O'Keefe C, McDevitt MA, Maciejewski JP 2010. Copy neutral loss of heterozygosity: a novel chromosomal lesion in myeloid malignancies. Blood 115:2731–39
    [Google Scholar]
  95. 95. 
    Panning B. 2008. X-chromosome inactivation: the molecular basis of silencing. J. Biol. 7:30
    [Google Scholar]
  96. 96. 
    Papavassiliou P, Charalsawadi C, Rafferty K, Jackson-Cook C 2015. Mosaicism for trisomy 21: a review. Am. J. Med. Genet. A 167A:26–39
    [Google Scholar]
  97. 97. 
    Peters AH, Kubicek S, Mechtler K, O'Sullivan RJ, Derijck AA et al. 2003. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol. Cell 12:1577–89
    [Google Scholar]
  98. 98. 
    Potter H, Chial HJ, Caneus J, Elos M, Elder N et al. 2019. Chromosome instability and mosaic aneuploidy in neurodegenerative and neurodevelopmental disorders. Front. Genet. 10:1092
    [Google Scholar]
  99. 99. 
    Pyott SM, Pepin MG, Schwarze U, Yang K, Smith G, Byers PH 2011. Recurrence of perinatal lethal osteogenesis imperfecta in sibships: parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance. Genet. Med. 13:125–30
    [Google Scholar]
  100. 100. 
    Quail MA, Smith M, Coupland P, Otto TD, Harris SR et al. 2012. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genom 13:341
    [Google Scholar]
  101. 101. 
    Rech GE, Sanz-Martin JM, Anisimova M, Sukno SA, Thon MR 2014. Natural selection on coding and noncoding DNA sequences is associated with virulence genes in a plant pathogenic fungus. Genome Biol. Evol. 6:2368–79
    [Google Scholar]
  102. 102. 
    Richardson BC. 2008. Epigenetics and autoimmunity. Autoimmunity 41:243–44
    [Google Scholar]
  103. 103. 
    Risques RA, Kennedy SR. 2018. Aging and the rise of somatic cancer-associated mutations in normal tissues. PLOS Genet 14:e1007108
    [Google Scholar]
  104. 104. 
    Roberts RJ, Carneiro MO, Schatz MC 2013. The advantages of SMRT sequencing. Genome Biol 14:405
    [Google Scholar]
  105. 105. 
    Ross MG, Russ C, Costello M, Hollinger A, Lennon NJ et al. 2013. Characterizing and measuring bias in sequence data. Genome Biol 14:R51
    [Google Scholar]
  106. 106. 
    Roth DB. 2014. V(D)J recombination: mechanism, errors, and fidelity. Microbiol. Spectr. 2:MDNA3-0041–2014
    [Google Scholar]
  107. 107. 
    Ryland GL, Doyle MA, Goode D, Boyle SE, Choong DY et al. 2015. Loss of heterozygosity: What is it good for. ? BMC Med. Genom. 8:45
    [Google Scholar]
  108. 108. 
    Sharp PM, Averof M, Lloyd AT, Matassi G, Peden JF 1995. DNA sequence evolution: the sounds of silence. Philos. Trans. R. Soc. B. 349:241–47
    [Google Scholar]
  109. 109. 
    Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP et al. 2013. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N. Engl. J. Med. 368:1971–79
    [Google Scholar]
  110. 110. 
    Soellner L, Begemann M, Mackay DJ, Gronskov K, Tumer Z et al. 2017. Recent advances in imprinting disorders. Clin. Genet. 91:3–13
    [Google Scholar]
  111. 111. 
    Sohn JI, Nam JW. 2018. The present and future of de novo whole-genome assembly. Brief. Bioinform. 19:23–40
    [Google Scholar]
  112. 112. 
    Spinner NB, Conlin LK. 2014. Mosaicism and clinical genetics. Am. J. Med. Genet. C 166C:397–405
    [Google Scholar]
  113. 113. 
    Stewart C, Kural D, Stromberg MP, Walker JA, Konkel MK et al. 2011. A comprehensive map of mobile element insertion polymorphisms in humans. PLOS Genet 7:e1002236
    [Google Scholar]
  114. 114. 
    Stewart JB, Chinnery PF. 2015. The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease. Nat. Rev. Genet. 16:530–42
    [Google Scholar]
  115. 115. 
    Stock S, Schmitt M, Sellner L 2019. Optimizing manufacturing protocols of chimeric antigen receptor T cells for improved anticancer immunotherapy. Int. J. Mol. Sci. 20:6223
    [Google Scholar]
  116. 116. 
    Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A et al. 2015. An integrated map of structural variation in 2,504 human genomes. Nature 526:75–81
    [Google Scholar]
  117. 117. 
    Surani MA. 1998. Imprinting and the initiation of gene silencing in the germ line. Cell 93:309–12
    [Google Scholar]
  118. 118. 
    Szulwach KE, Chen P, Wang X, Wang J, Weaver LS et al. 2015. Single-cell genetic analysis using automated microfluidics to resolve somatic mosaicism. PLOS ONE 10:e0135007
    [Google Scholar]
  119. 119. 
    Talens RP, Christensen K, Putter H, Willemsen G, Christiansen L et al. 2012. Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs. Aging Cell 11:694–703
    [Google Scholar]
  120. 120. 
    Tjio JH, Levan A. 1956. The chromosome number of man. Hereditas 42:1–6
    [Google Scholar]
  121. 121. 
    Toutain J, Goutte-Gattat D, Horovitz J, Saura R 2018. Confined placental mosaicism revisited: impact on pregnancy characteristics and outcome. PLOS ONE 13:e0195905
    [Google Scholar]
  122. 122. 
    Tubio JM. 2015. Somatic structural variation and cancer. Brief. Funct. Genom. 14:339–51
    [Google Scholar]
  123. 123. 
    Vorsanova SG, Yurov YB, Iourov IY 2010. Human interphase chromosomes: a review of available molecular cytogenetic technologies. Mol. Cytogenet. 3:1
    [Google Scholar]
  124. 124. 
    Wallace K, Grau MV, Levine AJ, Shen L, Hamdan R et al. 2010. Association between folate levels and CpG island hypermethylation in normal colorectal mucosa. Cancer Prev. Res. 3:1552–64
    [Google Scholar]
  125. 125. 
    Wan TS. 2014. Cancer cytogenetics: methodology revisited. Ann. Lab. Med. 34:413–25
    [Google Scholar]
  126. 126. 
    Wan TS, Ma ES. 2012. Molecular cytogenetics: an indispensable tool for cancer diagnosis. Chang Gung Med. J. 35:96–110
    [Google Scholar]
  127. 127. 
    Weischenfeldt J, Symmons O, Spitz F, Korbel JO 2013. Phenotypic impact of genomic structural variation: insights from and for human disease. Nat. Rev. Genet. 14:125–38
    [Google Scholar]
  128. 128. 
    Weiss RA. 1984. Human retroviruses in health and disease. Princess Takamatsu Symp 15:3–12
    [Google Scholar]
  129. 129. 
    Wutz A, Gribnau J. 2007. X inactivation Xplained. Curr. Opin. Genet. Dev. 17:387–93
    [Google Scholar]
  130. 130. 
    Xu C. 2018. A review of somatic single nucleotide variant calling algorithms for next-generation sequencing data. Comput. Struct. Biotechnol. J. 16:15–24
    [Google Scholar]
  131. 131. 
    Yokoyama Y, Narahara K, Kamada M, Tsuji K, Seino Y 1992. Tissue-specific mosaicism for trisomy 21 and congenital heart disease. J. Pediatr. 121:80–82
    [Google Scholar]
  132. 132. 
    Zhou W, Machiela MJ, Freedman ND, Rothman N, Malats N et al. 2016. Mosaic loss of chromosome Y is associated with common variation near TCL1A. Nat. Genet 48:563–68
    [Google Scholar]
  133. 133. 
    Zlotogora J. 1998. Germ line mosaicism. Hum. Genet. 102:381–86
    [Google Scholar]
/content/journals/10.1146/annurev-genet-041720-093403
Loading
/content/journals/10.1146/annurev-genet-041720-093403
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error