Chromosomal mosaicism is the presence of 2 or more cell lines with different karyotypes in the same individual. Mosaic karyotypes are a remarkable feature of early stages of human embryo development. They result from mitotic errors in chromosome segregation and demonstrate the clearest example of somatic mutagenesis in human beings. This review is devoted to the classification of chromosomal mosaicism and the analysis of its underlying mechanisms, incidence and phenotypic effects during embryo development. A model for tissue-specific aneuploid cell line compartmentalization in spontaneous abortions is introduced.

1.
Bacino CA, Schreck R, Fischel-Ghosdian N, Pepkowitz S, Prezant TR, Graham JM: Clinical and molecular studies in full trisomy 22: Further delineation of the phenotype and review of the literature. Am J Med Genet 56:359–365 (1995).
2.
Be CR, Velasquez PM, Youlton RR: A cytogenetic study in 609 abortions. Rev Med Chile 125:317–322 (1997).
3.
Benkhalifa M, Kasakyan S, Clement P, Baldi M, Tachdjian G, et al: Array comparative genomic hybridization profiling of first-trimester spontaneous abortions that fail to grow in vitro. Prenat Diagn 25:894–900 (2005).
4.
Bischoff FZ, Zenger-Hain J, Moses D, Van Dyke DL, Shaffer LG: Mosaicism for trisomy 12: four cases with varying outcomes. Prenat Diagn 15:1017–1026 (1995).
5.
Brajenovic-Milic B, Petrovic O, Krasevic M, Ristic S, Kapovic M: Chromosomal anomalies in abnormal human pregnancies. Fetal Diagn Therapy 13:187–191 (1998).
6.
Bugge M, Collins A, Petersen MB, Fisher J, Brandt C, et al: Non-disjunction of chromosome 18. Hum Mol Genet 7:661–668 (1998).
7.
Christian SL, Smith AC, Macha M, Black C, Elder FF, et al: Prenatal diagnosis of uniparental disomy 15 following trisomy 15 mosaicism. Prenat Diagn 16:323–332 (1996).
8.
Crane JP, Cheung SW: An embryonic model to explain cytogenetic inconsistencies observed in chorionic villus versus fetal tissue. Prenat Diagn 8:119–129 (1988).
9.
Daniely M, Aviram-Goldring A, Barkai G, Goldman B: Detection of chromosomal aberration in fetuses arising from recurrent spontaneous abortion by comparative genomic hybridization. Hum Reprod 13:805–809 (1998).
10.
De Brasi D, Genuardi M, D’Agostino A, Calvieri F, Tozzi C, et al: Double autosomal/gonosomal mosaic aneuploidy: Study of non-disjunction in two cases with trisomy of chromosome 8. Hum Genet 95:519–525 (1995).
11.
Delhanty JDA: Mechanisms of aneuploidy induction in human oogenesis and early embryogenesis. Cytogenet Genome Res 111:237–244 (2005).
12.
Delozier-Blanchet CD: Cytogenetic anomalies and placental function. Rev Fr Gynecol Obstet 86:723–729 (1991).
13.
Eiben B, Bartels I, Bähr-Porsch S, Borgmann S, Gatz G, et al: Cytogenetic analysis of 750 spontaneous abortions with the direct-preparation method of chorionic villi and its implications for studying genetic causes of pregnancy wastage. Am J Hum Genet 47:656–663 (1990).
14.
Fisher JM, Harvey JF, Morton NE, Jacobs PA: Trisomy 18: studies of the parent and cell division of origin and the effect of aberrant recombination on nondisjunction. Am J Hum Genet 56:669–675 (1995).
15.
Ford CE: Mosaicism and chimaeras. Br Med Bull 25:104–109 (1969).
16.
Genuardi M, Tozzi C, Pomponi M, Stagni M, Matteo DM, et al: Mosaic trisomy 17 in amniocytes: phenotypic outcome, tissue distribution, and uniparental disomy studies. Eur J Hum Genet 7:421–426 (1997).
17.
Griffin DK, Millie EA, Redline RW, Hassold TJ, Zaragoza MV: Cytogenetic analysis of spontaneous abortions: Comparison of techniques and assessment of the incidence of confined placental mosaicism. Am J Med Genet 72:297–301 (1997).
18.
Guerneri S, Bettio D, Simoni G, Brambati B, Lanzani A, Fraccaro M: Prevalence and distribution of chromosome abnormalities in a sample of first trimester internal abortions. Hum Reprod 2:735–739 (1987).
19.
Hahnemann JM, Vejerslev LO: European collaborative research on mosaicism in CVS (EUROCROMIC) – fetal and extrafetal cell lineages in 192 gestations with CVS mosaicism involving single autosomal trisomy. Am J Med Genet 70:179–187 (1997).
20.
Hassold T, Hunt P: To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2:280–291 (2001).
21.
Hassold T, Takaesu N: Analysis of non-disjunction in human trisomic spontaneous abortions. Prog Clin Biol Res 311:115–134 (1989).
22.
Hassold T, Chen N, Funkhouser J, Jooss T, Manuel B, et al: A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet 44:151–178 (1980).
23.
Hassold T, Jacobs PA, Leppert M, Sheldon M: Cytogenetic and molecular studies of trisomy 13. J Med Genet 24:725–732 (1987).
24.
Hassold T, Pettay D, Freeman SD, Grantham M, Takaesu N: Molecular studies of non-disjunction in trisomy 16. J Med Genet 28:159–162 (1991).
25.
Hassold T, Merrill M, Adkins K, Freeman S, Sherman S: Recombination and maternal-age dependent nondisjunction: molecular studies of trisomy 16. Am J Hum Genet 57:867–874 (1995).
26.
James RS, Jacobs PA: Molecular studies of the aetiology of trisomy 8 in spontaneous abortions and the liveborn population. Hum Genet 97:283–286 (1996).
27.
Kajii T, Ferrier A, Niikawa N, Takahara H, Ohama K, Avirachan S: Anatomic and chromosomal abnormalities in 639 spontaneous abortuses. Hum Genet 55:87–98 (1980).
28.
Kalousek DK: Pathogenesis of chromosomal mosaicism and its effect on early human development. Am J Hum Genet 91:39–45 (2000).
29.
Kalousek DK, Dill FJ: Chromosomal mosaicism confined to the placenta in human conceptions. Science 221:665–667 (1983).
30.
Kalousek DK, Barrett IJ, McGillivray BC: Placental mosaicism and intrauterine survival of trisomies 13 and 18. Am J Hum Genet 44:338–343 (1989).
31.
Kalousek DK, Barrett IJ, Gärtner AB: Spontaneous abortions and confined placental mosaicism. Hum Genet 88:642–646 (1992).
32.
Kalousek DK, Langlois S, Robison WP, Telenius A, Bernard L, et al: Trisomy 7 CVS mosaicism: pregnancy outcome, placental and DNA analysis in 14 cases. Am J Med Genet 65:348–352 (1996).
33.
Karadima G, Bugge M, Nicolaidis P, Vassilopoulos D, Avramopoulos D, et al: Origin of non-disjunction in trisomy 8 and trisomy 8 mosaicism. Eur J Hum Genet 6:432–438 (1998).
34.
Kline J, Stein Z: Epidemiology of chromosomal anomalies in spontaneous abortion: Prevalence, manifestation and determinants, in Bennett MJ, Edmonds DK (eds): Spontaneous and Recurrent Abortion, pp 29–50 (Blackwell Scientific Publishers, Oxford 1987).
35.
Lamb NE, Freeman SB, Savage-Austin A, Pettay D, Taft L, Hersey J: Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II. Nat Genet 14:400–405 (1996).
36.
Lebedev IN, Ostroverkhova NV, Nikitina TV, Sukhanova NN, Nazarenko SA: Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis. Eur J Hum Genet 12:513–520 (2004).
37.
Ledbetter DH, Zachary JM, Simpson JL, Golbus MS, Pergament E, et al: Cytogenetic results from the U.S. collaborative study on CVS. Prenat Diagn 12:317–345 (1992).
38.
Lestou VS, Kalousek DK: Confined placental mosaicism and intrauterine fetal growth. Arch Dis Child Fetal Neonatal Ed 79:223–226 (1998).
39.
Menasha J, Levy B, Hirschhorn K, Kardon NB: Incidence and spectrum of chromosomal abnormalities in spontaneous abortions: New insights from a 12-year study. Genet Med 7:251–263 (2005).
40.
Meulenbroeck GHM, Geraedts JPM: Parental origin of chromosome abnormalities in spontaneous abortions. Hum Genet 62:129–133 (1982).
41.
Minelli E, Buchi C, Granata P, Meroni E, Righi R, et al: Cytogenetic findings in echographically defined blighted ovum abortions. Ann Genet 36:107–110 (1993).
42.
Nicolaidis P, Petersen MB: Origin and mechanisms of non-disjunction in human autosomal trisomies. Hum Reprod 13:313–319 (1998).
43.
Ohno M, Maeda T, Matsunobi A: A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi. Obstet Gynecol 77:394–398 (1991).
44.
Pangalos C, Avramopoulos D, Blouin JL, Raoul O, de Blois MC, et al: Understanding mechanism(s) of mosaic trisomy 21 by using DNA polymorphism analysis. Am J Hum Genet 54:473–481 (1994).
45.
Rehder H, Coerdt W, Eggert R, Klink F, Schwinger E: Is there a correlation between morphological and cytogenetic findings in placental tissue from early missed abortions? Hum Genet 82:377–385 (1989).
46.
Robinson WP, Barrett IJ, Bernard L, Telenius A, Bernasconi F, 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 60:917–927 (1997).
47.
Robinson WP, Bernasconi F, Lau A, McFadden DE: Frequency of meiotic trisomy depends on involved chromosome and mode of ascertainment. Am J Med Genet 88:34–42 (1999).
48.
Sherman SL, Takaesu N, Freeman SB, Grantham M, Phillips C, et al: Trisomy 21: association between reduced recombination and non-disjunction. Am J Hum Genet 49:608–620 (1991).
49.
Simoni G, Sirchia SM: Confined placental mosaicism. Prenat Diagn 14:1185–1189 (1994).
50.
Takahara H, Ohama K, Fujiwara A: Cytogenetic study in early spontaneous abortions. Hiroshima J Med Sc 26:291–296 (1977).
51.
Trisomy 15 CPM: probable origins, pregnancy outcome and risk of fetal UPD: European Collaborative Research on Mosaicism in CVS (EUCROMIC). Prenat Diagn 19:29–35 (1999).
52.
Vorsanova SG, Kolotii AD, Iourov IY, Monakhov VV, Kirillova EA, et al: Evidence for high frequency of chromosomal mosaicism in spontaneous abortions revealed by interphase FISH analysis. J Histochem Cytochem 53:375–380 (2005).
53.
Warburton D, Fraser FC: Spontaneous abortion risks in man: data from reproductive histories in a medical genetics unit. Am J Hum Genet 16:1–24 (1964).
54.
Warburton D, Yu CY, Kline J, Stein Z: Mosaic autosomal trisomy in cultures from spontaneous abortions. Am J Hum Genet 30:609–617 (1978).
55.
Wilkinson TA, James RS, Crolla JA, Cockwell AE, Cambell PL, Temple IK: A case of maternal uniparental disomy of chromosome 9 in association with confined placental mosaicism for trisomy 9. Prenat Diagn 16:371–374 (1996).
56.
Wolstenholme J: Confined placental mosaicism for trisomies 2, 3, 7, 8, 9, 16 and 22: their incidence, likely origins and mechanisms for cell lineage compartmentalization. Prenat Diagn 16:511–524 (1996).
57.
Wolstenholme J, Rooney DE, Davison EV: Confined placental mosaicism, IUGR and adverse pregnancy outcome: a controlled retrospective U.K. collaborative study. Prenat Diagn 14:345–361 (1994).
58.
Zaragoza MV, Jacobs PA, James RS, Rogan P, Sherman S, Hassold TJ: Nondisjunction of human acrocentric chromosomes: studies of 432 fetuses and liveborns. Hum Genet 94:411–417 (1994).
59.
Zaragoza MV, Millie E, Redline RW, Hassold TJ: Studies of non-disjunction in trisomies 2, 7, 15 and 22: does the parental origin of trisomy influence placental morphology? J Med Genet 35:924–931 (1998).
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