Formation of Small Supernumerary Marker Chromosomes



In general, not much is known about the exact mode of small supernumerary marker chromosome (sSMC) formation. Especially, when, why, and how during gametogenesis or embryogenesis an sSMC evolves is unclear. Nonetheless, for all kinds of sSMC shapes there are models for how they could be formed. These ideas are based in part on the finding that uniparental disomy and sSMC can show up together and on the observation that sSMC can evolve by incomplete trisomic rescue. Overall, an sSMC is formed by the combination of one or more rare events happening during gametogenesis or embryogenesis. This chapter sumarizes what is known on the formation of multiple sSMC compared with single sSMC, on inverted duplicated, centric minute-shaped, and ring-shaped sSMC evolution, on the mixtures of different sSMC shapes, and on centromeric activity of dicentric sSMC and breakpoint characteristics of sSMC.


Karyotypic Evolution Derivative Chromosome Copy Number Variant Region Chromosome Fragmentation Active Centromere 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Augui S, Filion GJ, Huart S, Nora E, Guggiari M, Maresca M, Stewart AF, Heard E (2007) Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic. Science 318:1632–1636PubMedCrossRefGoogle Scholar
  2. Baldwin EL, May LF, Justice AN, Martin CL, Ledbetter DH (2008) Mechanisms and consequences of small supernumerary marker chromosomes: from Barbara McClintock to modern genetic-counseling issues. Am J Hum Genet 82:398–410PubMedCrossRefGoogle Scholar
  3. Bán Z, Nagy B, Papp C, Beke A, Tóth-Pál E, Papp Z (2003) Recurrent trisomy 21 and uniparental disomy 21 in a family. Fetal Diagn Ther 18:454–458PubMedCrossRefGoogle Scholar
  4. Bartels I, Schlueter G, Liehr T, von Eggeling F, Starke H, Glaubitz R, Burfeind P (2003) Supernumerary small marker chromosome (SMC) and uniparental disomy 22 in a child with confined placental mosaicism of trisomy 22: trisomy rescue due to marker chromosome formation. Cytogenet Genome Res 101:103–105PubMedCrossRefGoogle Scholar
  5. Beverstock GC, Bezrookove V, Mollevanger P, van de Kamp JJ, Pearson P, Kouwenberg JM, Rosenberg C (2003) Multiple supernumerary ring chromosomes of different origin in a patient: a clinical report and review of the literature. Am J Med Genet A 122:168–173CrossRefGoogle Scholar
  6. Carter MT, St Pierre SA, Zackai EH, Emanuel BS, Boycott KM (2009) Phenotypic delineation of Emanuel syndrome (supernumerary derivative 22 syndrome): clinical features of 63 individuals. Am J Med Genet A 149:1712–1721Google Scholar
  7. Daniel A, Malafiej P (2003) A series of supernumerary small ring marker autosomes identified by FISH with chromosome probe arrays and literature review excluding chromosome 15. Am J Med Genet A 117:212–222CrossRefGoogle Scholar
  8. Dewald GW (1983) Isodicentric X chromosomes in humans: origin, segregation behaviour, and replication band patterns. In: Sandberg AA (ed) Cytogenetics of the mammalian X chromosome, part A. Liss, New York, pp 405–426Google Scholar
  9. Ewers E, Yoda K, Hamid AB, Weise A, Manvelyan M, Liehr T (2010) Centromere activity in dicentric small supernumerary marker chromosomes. Chromosome Res 18:555–562PubMedCrossRefGoogle Scholar
  10. Fang YY, Eyre HJ, Bohlander SK, Estop A, McPherson E, Trager T, Riess O, Callen DF (1995) Mechanisms of small ring formation suggested by the molecular characterization of two small accessory ring chromosomes derived from chromosome 4. Am J Hum Genet 57:1137–1142PubMedGoogle Scholar
  11. Farfalli VI, Magli MC, Ferraretti AP, Gianaroli L (2007) Role of aneuploidy on embryo implantation. Gynecol Obstet Invest 64:161–165PubMedCrossRefGoogle Scholar
  12. Felka T, Lemke J, Lemke C, Michel S, Liehr T, Claussen U (2007) DNA degradation during maturation of erythrocytes: molecular cytogenetic characterization of Howell-Jolly bodies. Cytogenet Genome Res 119:2–8PubMedCrossRefGoogle Scholar
  13. Ing PS, Lubinsky MS, Smith SD, Golden E, Sanger WG, Duncan A (1987) Cat-eye syndrome with different marker chromosomes in a mother and daughter. Am J Med Genet A 26:621–628CrossRefGoogle Scholar
  14. Iourov IY, Vorsanova SG, Yurov YB (2009) Developmental neural chromosome instability as a possible cause of childhood brain cancers. Med Hypotheses 72:615–616PubMedCrossRefGoogle Scholar
  15. Kalousek DK, Howard-Peebles PN, Olson SB, Barrett IJ, Dorfmann A, Black SH, Schulman JD, Wilson RD (1991) Confirmation of CVS mosaicism in term placentae and high frequency of intrauterine growth retardation association with confined placental mosaicism. Prenat Diagn 11:743–750PubMedCrossRefGoogle Scholar
  16. Liehr T (2006) Familial small supernumerary marker chromosomes are predominantly inherited via the maternal line. Genet Med 8:459–462PubMedCrossRefGoogle Scholar
  17. Liehr T (ed) (2009a) Fluorescence in situ hybridization (FISH): application guide. Springer, BerlinGoogle Scholar
  18. Liehr T (2010) Cytogenetic contribution to uniparental disomy (UPD). Mol Cytogenet 3:8PubMedCrossRefGoogle Scholar
  19. Liehr T, Pfeiffer RA, Trautmann U (1992) Typical and partial cat eye syndrome: identification of the marker chromosome by FISH. Clin Genet 42:91–96PubMedCrossRefGoogle Scholar
  20. Liehr T, Claussen U, Starke H (2004) Small supernumerary marker chromosomes (sSMC) in humans. Cytogenet Genome Res 107:55–67PubMedCrossRefGoogle Scholar
  21. Liehr T, Starke H, Heller A, Kosyakova N, Mrasek K, Gross M, Karst C, Steinhaeuser U, Hunstig F, Fickelscher I, Kuechler A, Trifonov V, Romanenko SA, Weise A (2006a) Multicolor fluorescence in situ hybridization (FISH) applied for FISH-banding. Cytogenet Genome Res 114:240–244PubMedCrossRefGoogle Scholar
  22. Liehr T, Mrasek K, Weise A, Dufke A, Rodríguez L, Martínez Guardia N, Sanchís A, Vermeesch JR, Ramel C, Polityko A, Haas OA, Anderson J, Claussen U, von Eggeling F, Starke H (2006b) Small supernumerary marker chromosomes: progress towards a genotype-phenotype correlation. Cytogenet Genome Res 112:23–34PubMedCrossRefGoogle Scholar
  23. Liehr T, Starke H, Senger G, Melotte C, Weise A, Vermeesch JR (2006c) Overrepresentation of small supernumerary marker chromosomes (sSMC) from chromosome 6 origin in cases with multiple sSMC. Am J Med Genet A 140:46–51PubMedGoogle Scholar
  24. Liehr T, Utine GE, Trautmann U, Rauch A, Kuechler A, Pietrzak J, Bocian E, Kosyakova N, Mrasek K, Boduroglu K, Weise A, Aktas D (2007a) Neocentric small supernumerary marker chromosomes (sSMC): three more cases and review of the literature. Cytogenet Genome Res 118:31–37PubMedCrossRefGoogle Scholar
  25. Liehr T, Mrasek K, Hinreiner S, Reich D, Ewers E, Bartels I, Seidel J, Emmanuil N, Petesen M, Polityko A, Dufke A, Iourov I, Trifonov V, Vermeesch J, Weise A (2007b) Small supernumerary marker chromosomes (sSMC) in patients with a 45, X/46, X,+mar karyotype: 17 new cases and a review of the literature. Sex Dev 1:353–362PubMedCrossRefGoogle Scholar
  26. Los FJ, van Opstal D, van den Berg C, Braat AP, Verhoef S, Wesby-van Swaay E, van den Ouweland AM, Halley DJ (1998) Uniparental disomy with and without confined placental mosaicism: a model for trisomic zygote rescue. Prenat Diagn 18:659–668PubMedCrossRefGoogle Scholar
  27. Magenis RE, Sheehy RR, Brown MG, McDermid HE, White BN, Zonana J, Weleber R (1988) Parental origin of the extra chromosome in the cat eye syndrome: evidence from heteromorphism and in situ hybridization analysis. Am J Med Genet A 29:9–19CrossRefGoogle Scholar
  28. Mefford HC, Eichler EE (2009) Duplication hotspots, rare genomic disorders, and common disease. Curr Opin Genet Dev 19:196–204PubMedCrossRefGoogle Scholar
  29. Michalski K, Rauer M, Williamson N, Perszyk A, Hoo JJ (1993) Identification, counselling, and outcome of two cases of prenatally diagnosed supernumerary small ring chromosomes. Am J Med Genet A 46:88–94CrossRefGoogle Scholar
  30. Migeon BR, Jeppesen P, Torchia BS, Fu S, Dunn MA, Axelman J, Schmeckpeper BJ, Fantes J, Zori RT, Driscoll DJ (1996) Lack of X inactivation associated with maternal X isodisomy: evidence for a counting mechanism prior to X inactivation during human embryogenesis. Am J Hum Genet 58:161–170PubMedGoogle Scholar
  31. Mrasek K, Schoder C, Teichmann AC, Behr K, Franze B, Wilhelm K, Blaurock N, Claussen U, Liehr T, Weise A (2010) Global screening and extended nomenclature for 230 aphidicolin-inducible fragile sites, including 61 yet unreported ones. Int J Oncol 36:929–940PubMedGoogle Scholar
  32. Mukherjee AB, Murty VV, Rodriguez E, Reuter VE, Bosl GJ, Chaganti RS (1991) Detection and analysis of origin of i(12p), a diagnostic marker of human male germ cell tumors, by fluorescence in situ hybridization. Genes Chromosomes Cancer 3:300–307PubMedCrossRefGoogle Scholar
  33. Murmann AE, Conrad DF, Mashek H, Curtis CA, Nicolae RI, Ober C, Schwartz S (2009) Inverted duplications on acentric markers: mechanism of formation. Hum Mol Genet 18:2241–2256PubMedCrossRefGoogle Scholar
  34. Narahara K, Hiramoto K, Murakami M, Miyake S, Tsuji K, Yokoyama Y, Namba H, Ninomiya S, Murakami R, Seino Y (1992) Unique karyotypes in two patients with Prader-Willi syndrome. Am J Med Genet A 42:671–677CrossRefGoogle Scholar
  35. Ramirez-Duenas ML, Gonzalez GJ (1992) fra(1)(p11), fra(1)(q22) and r(1)(p11q22) in a retarded girl. Ann Genet 35:178–182PubMedGoogle Scholar
  36. Schreck RR, Breg WR, Erlanger BF, Miller OJ (1977) Preferential derivation of abnormal human G-group-like chromosomes from chromosome 15. Hum Genet 36:1–12PubMedCrossRefGoogle Scholar
  37. Sheth F, Ewers E, Kosyakova N, Weise A, Sheth J, Patil S, Ziegler M, Liehr T (2009) A neocentric isochromosome Yp present as additional small supernumerary marker chromosome: evidence against U-type exchange mechanism? Cytogenet Genome Res 125:115–116PubMedCrossRefGoogle Scholar
  38. Stankiewicz P, Brozek I, Helias-Rodzewicz Z, Wierzba J, Pilch J, Bocian E, Balcerska A, Wozniak A, Kardas I, Wirth J, Mazurczak T, Limon J (2001) Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Am J Med Genet A 101:226–239CrossRefGoogle Scholar
  39. Starke H, Mitulla B, Beensen V, Trifonov V, Rubtsov N, Heller A, Ziegler M, Neumann A, Claussen U, Liehr T (2003) First postnatal case of mosaic del(22)/r(22). Prenat Diagn 23:765–767PubMedCrossRefGoogle Scholar
  40. Stavropoulou C, Mignon C, Delobel B, Moncla A, Depetris D, Croquette MF, Mattei MG (1998) Severe phenotype resulting from an active ring X chromosome in a female with a complex karyotype: characterisation and replication study. J Med Genet 35:932–938PubMedCrossRefGoogle Scholar
  41. Stefanou EG, Crocker M (2004) A chromosome 21-derived minute marker in a mosaic trisomy 21 background: implications for risk assessments in marker chromosome cases. Am J Med Genet A 127:191–193CrossRefGoogle Scholar
  42. Sullivan BA, Willard HF (1998) Stable dicentric X chromosomes with two functional centromeres. Nat Genet 20:227–228PubMedCrossRefGoogle Scholar
  43. Trifonov V, Fluri S, Binkert F, Nandini A, Anderson J, Rodriguez L, Gross M, Kosyakova N, Mkrtchyan H, Ewers E, Reich D, Weise A, Liehr T (2008) Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated entity? Mol Cytogenet 1:6PubMedCrossRefGoogle Scholar
  44. Vialard F, Molina-Gomes D, Quarello E, Leroy B, Ville Y, Selva J (2009) Partial chromosome deletion: a new trisomy rescue mechanism? Fetal Diagn Ther 25:111–114PubMedCrossRefGoogle Scholar
  45. Wang NJ, Parokonny AS, Thatcher KN, Driscoll J, Malone BM, Dorrani N, Sigman M, LaSalle JM, Schanen NC (2008) Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15. BMC Genet 9:2PubMedCrossRefGoogle Scholar
  46. Wu TF, Chu DS (2008) Epigenetic processes implemented during spermatogenesis distinguish the paternal pronucleus in the embryo. Reprod Biomed Online 16:13–22PubMedCrossRefGoogle Scholar
  47. Zhang F, Gu W, Hurles ME, Lupski JR (2009) Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet 10:451–481PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Institut für HumangenetikUniversitätsklinikum JenaJenaGermany

Personalised recommendations