Detecting somatic mosaicism: Considerations and clinical implications

Clinical Genetics

Volumn 87, Issue 6, 2015, Pages 554-562

  Cohen, A S A ^a,b   Wilson, S L ^a,b   Trinh, J ^a,c   Ye, X C ^a,b,d  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^d Centre for Molecular Medicine and Therapeutics   (Canada)

Author keywords

Aneuploidy; Cancer; Genetic alteration; Genetic variation; High throughput sequencing; Mendelian disorders; Reversion; Somatic mosaicism; Somatic mutation

Indexed keywords

ANEUPLOIDY; AUTOSOMAL RECESSIVE DISORDER; CHROMOSOMAL INSTABILITY; CHROMOSOME ANALYSIS; CHROMOSOME DISORDER; GENETIC COUNSELING; GENETIC VARIABILITY; HUMAN; MICROARRAY ANALYSIS; MOLECULAR PATHOLOGY; MOSAICISM; NEXT GENERATION SEQUENCING; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SOMATIC MUTATION; SURVIVAL; CHROMOSOME ABERRATION; COMPARATIVE GENOMIC HYBRIDIZATION; GENETIC ASSOCIATION; GENETIC SCREENING; GENOMICS; HIGH THROUGHPUT SEQUENCING; PROCEDURES;

ANEUPLOIDY; CHROMOSOME ABERRATIONS; COMPARATIVE GENOMIC HYBRIDIZATION; GENETIC ASSOCIATION STUDIES; GENETIC COUNSELING; GENETIC TESTING; GENOMICS; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MOSAICISM; PHENOTYPE;

EID: 84928770050     PISSN: 00099163     EISSN: 13990004     Source Type: Journal    
DOI: 10.1111/cge.12502     Document Type: Review

References (91)

1. Biesecker LG, Spinner NB. A genomic view of mosaicism and human disease. Nat Rev Genet 2013: 14: 307-320.
2. Bianchi DW, Lo YM. Fetomaternal cellular and plasma DNA trafficking: the Yin and the Yang. Ann N Y Acad Sci 2001: 945: 119-131.
3. Van Dijk BA, Boomsma DI, de Man AJ. Blood group chimerism in human multiple births is not rare. Am J Med Genet 1996: 61: 264-268.
4. Lupski JR. Genetics. Genome mosaicism - one human, multiple genomes. Science 2013: 341: 358-359.
5. Seshadri R, Kutlaca RJ, Trainor K, Matthews C, Morley AA. Mutation rate of normal and malignant human lymphocytes. Cancer Res 1987: 47: 407-409.
6. De S. Somatic mosaicism in healthy human tissues. Trends Genet 2011: 27: 217-223.
7. Frank SA. Somatic mosaicism and disease. Curr Biol 2014: 24: R577-R581.
8. Li R, Montpetit A, Rousseau M et al. Somatic point mutations occurring early in development: a monozygotic twin study. J Med Genet 2014: 51: 28-34.
9. Avner P, Heard E. X-chromosome inactivation: counting, choice and initiation. Nat Rev Genet 2001: 2: 59-67.
10. Beutler E, Yeh M, Fairbanks VF. The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD-deficiency as a marker. Proc Natl Acad Sci U S A 1962: 48: 9-16.
11. Ngai YF, Chijiwa C, Mercimek-Mahmutoglu S et al. Pseudohypoparathyroidism type 1a and the GNAS p.R231H mutation: somatic mosaicism in a mother with two affected sons. Am J Med Genet A 2010: 152A: 2784-2790.
12. Youssoufian H, Pyeritz RE. Mechanisms and consequences of somatic mosaicism in humans. Nat Rev Genet 2002: 3: 748-758.
13. Gottlieb B, Beitel LK, Trifiro MA. Somatic mosaicism and variable expressivity. Trends Genet 2001: 17: 79-82.
14. Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J Am Acad Dermatol 1987: 16: 899-906.
15. Weleber RG, Zonana J. Iris hamartomas (Lisch nodules) in a case of segmental neurofibromatosis. Am J Ophthalmol 1983: 96: 740-743.
16. Knudson AG. Two genetic hits (more or less) to cancer. Nat Rev Cancer 2001: 1: 157-162.
17. Erickson RP. Recent advances in the study of somatic mosaicism and diseases other than cancer. Curr Opin Genet Dev 2014: 26C: 73-78.
18. Lindhurst MJ, Sapp JC, Teer JK et al. A mosaic activating mutation in AKT1 associated with the proteus syndrome. N Engl J Med 2011: 365: 611-619.
19. Lee JH, Huynh M, Silhavy JL et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat Genet 2012: 44: 941-945.
20. Rivière J-B, Mirzaa GM, O'Roak BJ et al. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet 2012: 44: 934-940.
21. Asthagiri AR, Parry DM, Butman JA et al. Neurofibromatosis type 2. Lancet 2009: 373: 1974-1986.
22. Kehrer-Sawatzki H, Kluwe L, Sandig C et al. High frequency of mosaicism among patients with neurofibromatosis type 1 (NF1) with microdeletions caused by somatic recombination of the JJAZ1 gene. Am J Hum Genet 2004: 75: 410-423.
23. Erickson RP. Somatic gene mutation and human disease other than cancer: an update. Mutat Res 2010: 705: 96-106.
24. Lindhurst MJ, Parker VER, Payne F et al. Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nat Genet 2012: 44: 928-933.
25. Cohen ASA, Townsend KN, Xiang Q-S et al. Somatic mosaicism for the p.His1047Arg mutation in PIK3CA in a girl with mesenteric lipomatosis. Am J Med Genet A 2014: 164 (9): 2360-2364.
26. Gearhart JD, Davisson MT, Oster-Granite ML. Autosomal aneuploidy in mice: generation and developmental consequences. Brain Res Bull 1986: 16: 789-801.
27. Robinson WP, Bernasconi F, Lau A, McFadden DE. Frequency of meiotic trisomy depends on involved chromosome and mode of ascertainment. Am J Med Genet 1999: 84: 34-42.
28. Williams BR, Prabhu VR, Hunter KE et al. Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells. Science 2008: 322: 703-709.
29. Nagaoka SI, Hassold TJ, Hunt PA. Human aneuploidy: mechanisms and new insights into an age-old problem. Nat Rev Genet 2012: 13: 493-504.
30. Kurahashi H, Tsutsumi M, Nishiyama S, Kogo H, Inagaki H, Ohye T. Molecular basis of maternal age-related increase in oocyte aneuploidy. Congenit Anom 2012: 52: 8-15.
31. Templado C, Uroz L, Estop A. New insights on the origin and relevance of aneuploidy in human spermatozoa. Mol Hum Reprod 2013: 19: 634-643.
32. Robinson WP, Bernasconi F, Mutirangura A et al. Nondisjunction of chromosome 15: origin and recombination. Am J Hum Genet 1993: 53: 740-751.
33. Robinson WP, Barrett IJ, Bernard L et al. Meiotic origin of trisomy in confined placental mosaicism is correlated with presence of fetal uniparental disomy, high levels of trisomy in trophoblast, and increased risk of fetal intrauterine growth restriction. Am J Hum Genet 1997: 60: 917-927.
34. Niemitz EL, Feinberg AP. Epigenetics and assisted reproductive technology: a call for investigation. Am J Hum Genet 2004: 74: 599-609.
35. Robinson WP. Mechanisms leading to uniparental disomy and their clinical consequences. Bioessays 2000: 22: 452-459.
36. Sasaki M, Lange J, Keeney S. Genome destabilization by homologous recombination in the germ line. Nat Rev Mol Cell Biol 2010: 11: 182-195.
37. Lieber MR. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 2010: 79: 181-211.
38. Thompson SL, Bakhoum SF, Compton DA. Mechanisms of chromosomal instability. Curr Biol 2010: 20: R285-R295.
39. German J. Bloom syndrome: a mendelian prototype of somatic mutational disease. Medicine (Baltimore) 1993: 72: 393-406.
40. Ellis NA, Groden J, Ye T-Z et al. The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 1995: 83: 655-666.
41. Ellis N, Ciocci S, German J. Back mutation can produce phenotype reversion in Bloom syndrome somatic cells. Hum Genet 2001: 108: 167-173.
42. Jonkman MF, Scheffer H, Stulp R et al. Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion. Cell 1997: 88: 543-551.
43. Waisfisz Q, Morgan NV, Savino M et al. Spontaneous functional correction of homozygous fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism. Nat Genet 1999: 22: 379-383.
44. Darling TN, Yee C, Bauer JW, Hintner H, Yancey KB. Revertant mosaicism: partial correction of a germ-line mutation in COL17A1 by a frame-restoring mutation. J Clin Invest 1999: 103: 1371-1377.
45. Hassold TJ, Jacobs PA. Trisomy in man. Annu Rev Genet 1984: 18: 69-97.
46. Naicker T, Aldous C. Two trisomy 22 live births in one hospital in 15 months: is it as rare as we thought? Fetal Pediatr Pathol 2014: 33: 35-41.
47. Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2001: 2: 280-291.
48. Fisher D, DiPietro A, Murdison KA, Lemieux CA. Full Monosomy 21: echocardiographic findings in the third molecularly confirmed case. Pediatr Cardiol 2013: 34: 733-735.
49. Burgess T, Downie L, Pertile MD et al. Monosomy 21 seen in live born is unlikely to represent true monosomy 21: a case report and review of the literature. Case Rep Genet 2014: 2014: 965401.
50. Toral-Lopez J, Gonzalez-Huerta LM, Cuevas-Covarrubias SA. Complete monosomy mosaic of chromosome 21: case report and review of literature. Gene 2012: 510 (2): 175-179.
51. Riccardi VM. Trisomy 8: an international study of 70 patients. Birth Defects Orig Artic Ser 1977: 13: 171-184.
52. Fagerberg CR, Eriksen FB, Thormann J, Østergaard JR. Trisomy 14 mosaicism: clinical and cytogenetic findings in an adult. Clin Dysmorphol 2012: 21: 45-47.
53. Benn P. Trisomy 16 and trisomy 16 Mosaicism: a review. Am J Med Genet 1998: 79: 121-133.
54. Daber R, Chapman KA, Ruchelli E et al. Mosaic trisomy 17: variable clinical and cytogenetic presentation. Am J Med Genet A 2011: 155A: 2489-2495.
55. Hirschhorn R. In vivo reversion to normal of inherited mutations in humans. J Med Genet 2003: 40: 721-728.
56. King WA, Coppola G, Alexander B et al. The impact of chromosomal alteration on embryo development. Theriogenology 2006: 65: 166-177.
57. Kvittingen EA, Rootwelt H, Berger R, Brandtzaeg P. Self-induced correction of the genetic defect in tyrosinemia type I. J Clin Invest 1994: 94: 1657-1661.
58. Koch G, Shows TB. Somatic cell genetics of adenosine deaminase expression and severe combined immunodeficiency disease in humans. Proc Natl Acad Sci U S A 1980: 77: 4211-4215.
59. Hirschhorn R, Yang DR, Puck JM, Huie ML, Jiang CK, Kurlandsky LE. Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency. Nat Genet 1996: 13: 290-295.
60. Kamischke A, Baumgardt A, Horst J, Nieschlag E. Clinical and diagnostic features of patients with suspected Klinefelter syndrome. J Androl 2003: 24: 41-48.
61. Nielsen J, Wohlert M. Chromosome abnormalities found among 34910 newborn children: results from a 13-year incidence study in Århus, Denmark. Hum Genet 1991: 87: 81-83.
62. Demaliaj E, Cerekja A, Piazze J. Sex Chromosome Aneuploidies. 2012. Retrieved 2012, from http://www.intechopen.com/books/aneuploidy-in-health-and-disease/sex-chromosome-aneuploidies
63. Sybert VP, McCauley E. Turner's syndrome. N Engl J Med 2004: 351: 1227-1238.
64. Hersmus R, Stoop H, Turbitt E et al. SRY mutation analysis by next generation (deep) sequencing in a cohort of chromosomal Disorders of Sex Development (DSD) patients with a mosaic karyotype. BMC Med Genet 2012: 13: 108.
65. Miller DT, Adam MP, Aradhya S et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010: 86: 749-764.
66. Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol 2008: 26: 1135-1145.
67. Pinto D, Darvishi K, Shi X et al. Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants. Nat Biotechnol 2011: 29: 512-520.
68. Conlin LK, Thiel BD, Bonnemann CG et al. Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. Hum Mol Genet 2010: 19: 1263-1275.
69. Ng SB, Buckingham KJ, Lee C et al. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 2010: 42: 30-35.
70. Gibson WT, Hood RL, Zhan SH et al. Mutations in EZH2 cause Weaver syndrome. Am J Hum Genet 2012: 90: 110-118.
71. Shirley MD, Tang H, Gallione CJ et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 2013: 368 (21): 1971-1979.
72. Kurek KC, Luks VL, Ayturk UM et al. Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am J Hum Genet 2012: 90: 1108-1115.
73. Moreau Y, Tranchevent L-C. Computational tools for prioritizing candidate genes: boosting disease gene discovery. Nat Rev Genet 2012: 13: 523-536.
74. Cooper GM, Shendure J. Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data. Nat Rev Genet 2011: 12: 628-640.
75. Gonzalez-Perez A, Mustonen V, Reva B et al. Computational approaches to identify functional genetic variants in cancer genomes. Nat Methods 2013: 10: 723-729.
76. Rohlin A, Wernersson J, Engwall Y, Wiklund L, Björk J, Nordling M. Parallel sequencing used in detection of mosaic mutations: comparison with four diagnostic DNA screening techniques. Hum Mutat 2009: 30: 1012-1020.
77. Qin W, Kozlowski P, Taillon BE et al. Ultra deep sequencing detects a low rate of mosaic mutations in tuberous sclerosis complex. Hum Genet 2010: 127: 573-582.
78. Koboldt DC, Steinberg KM, Larson DE, Wilson RK, Mardis ER. The next-generation sequencing revolution and its impact on genomics. Cell 2013: 155: 27-38.
79. Woodruff MF. Cellular heterogeneity in tumours. Br J Cancer 1983: 47: 589.
80. Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 2012: 12: 323-334.
81. Papavassiliou P, York TP, Gursoy N et al. The phenotype of persons having mosaicism for trisomy 21/Down syndrome reflects the percentage of trisomic cells present in different tissues. Am J Med Genet A 2009: 149: 573-583.
82. Taysi K, Kohn G, Mellman WJ. Mosaic mongolism. II. Cytogenetic studies. J Pediatr 1970: 76: 880-885.
83. Nazarenko SA, Timoshevsky VA, Sukhanova NN. High frequency of tissue-specific mosaicism in Turner syndrome patients. Clin Genet 1999: 56: 59-65.
84. Cho RJ. Rethinking the prosaicism of mosaicism; is it in us? Exp Dermatol 2010: 19: 1037-1039.
85. Russell LM, Strike P, Browne CE, Jacobs PA. X chromosome loss and ageing. Cytogenet Genome Res 2007: 116: 181-185.
86. Barazani Y, Agarwal A, Sabanegh ES. Functional sperm testing and the role of proteomics in the evaluation of male infertility. Urology 2014: 84: 255-261.
87. Kalousek DK, Dill FJ, Pantzar T, McGillivray BC, Yong SL, Wilson RD. Confined chorionic mosaicism in prenatal diagnosis. Hum Genet 1987: 77: 163-167.
88. Yuen RKC, Robinson WP. Review: a high capacity of the human placenta for genetic and epigenetic variation: implications for assessing pregnancy outcome. Placenta 2011: 32 (Suppl. 2): S136-S141.
89. Johnson A, Wapner RJ. Mosaicism: implications for postnatal outcome. Curr Opin Obstet Gynecol 1997: 9: 126-135.
90. Vissers LELM, Fano V, Martinelli D, et al. Whole-exome sequencing detects somatic mutations of IDH1 in metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA). Am J Med Genet A 2011: 155: 2609-2616.
91. Rios JJ, Paria N, Burns DK, et al. Somatic gain-of-function mutations in PIK3CA in patients with macrodactyly. Hum Mol Genet 2013: 22: 444-451.