Skip to main content
SpringerLink
Log in

Human ring chromosomes and small supernumerary marker chromosomes—do they have telomeres?

  • Published:
Chromosome Research Aims and scope Submit manuscript

Abstract

Ring chromosomes and small supernumerary marker chromosomes (sSMC) are enigmatic types of derivative chromosomes, in which the telomeres are thought to play a crucial role in their formation and stabilization. Considering that there are only a few studies that evaluate the presence of telomeric sequences in ring chromosomes and on sSMC, here, we analyzed 14 ring chromosomes and 29 sSMC for the presence of telomeric sequences through fluorescence in situ hybridization (FISH). The results showed that ring chromosomes can actually fall into two groups: the ones with or without telomeres. Additionally, telomeric signals were detectable at both ends of centric and neocentric sSMC with inverted duplication shape, as well as in complex sSMC. Apart from that, generally both ring- and centric minute-shaped sSMC did not present telomeric sequences neither detectable by FISH nor by a second protein-directed immunohistochemical approach. However, the fact that telomeres are absent does not automatically mean that the sSMC has a ring shape, as often deduced in the previous literature. Overall, the results obtained by FISH studies directed against telomeres need to be checked carefully by other approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

DAPI:

Diaminophenylindol

FISH:

Fluorescence in situ hybridization

FITC:

Fluorescein isothiocyanate

sSMC:

Small supernumerary marker chromosome(s)

subcenM-FISH:

Subcentromere-specific multicolor FISH

References

  • 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 82:398–410

    Article  PubMed  CAS  Google Scholar 

  • Beverstock GC, Bezrookove V, Mollevanger P et al (2003) Multiple supernumerary ring chromosomes of different origin in a patient: a clinical report and review of the literature. Am J Med Genet A 122A:168–173

    Article  PubMed  Google Scholar 

  • Brandt CA, Kierkegaard O, Hindkjaer J, Jensen PK, Pedersen S, Therkelsen AJ (1993) Ring chromosome 20 with loss of telomeric sequences detected by multicolour PRINS. Clin Genet 44:26–31

    Article  PubMed  CAS  Google Scholar 

  • Carbonari M, Cibati M, Sette N, Catizone A, Fiorilli M (2011) Measurement of telomere length using PNA probe by cytometry. Methods Cell Biol 103:189–202

    Article  PubMed  CAS  Google Scholar 

  • Cote GB, Katsantoni A, Deligeorgis D (1981) The cytogenetic and clinical implications of a ring chromosome 2. Ann Genet 24:231–235

    PubMed  CAS  Google Scholar 

  • Cotter PD, Drexler K, Corley AL et al (2005) Prenatal diagnosis of minute supernumerary marker chromosomes. Gynecol Obstet Invest 60:27–38

    Article  PubMed  CAS  Google Scholar 

  • Crolla JA (1998) FISH and molecular studies of autosomal supernumerary marker chromosomes excluding those derived from chromosome 15: II. Review of the literature. Am J Med Genet 75:367–381

    Article  PubMed  CAS  Google Scholar 

  • Esmer MC, Carnevale A, Gómez L, del Castillo V, Frías S (1996) Fluorescence in situ hybridization in 6 patients with alterations of chromosome 18 and in 7 with marker chromosomes. Rev Invest Clin 48:27–33, Spanish

    PubMed  CAS  Google Scholar 

  • Ewers E, Yoda K, Hamid AB, Weise A, Manvelyan M, Liehr T (2010) Centromere activity in dicentric small supernumerary marker chromosomes. Chromosome Res 18:555–562

    Article  PubMed  CAS  Google Scholar 

  • Fickelscher I, Starke H, Schulze E et al (2007) A further case with a small supernumerary marker chromosome (sSMC) derived from chromosome 1-evidence for high variability in mosaicism in different tissues of sSMC carriers. Prenat Diagn 27:783–785

    Article  PubMed  Google Scholar 

  • Fortin F, Beaulieu Bergeron M, Fetni R, Lemieux N (2009) Frequency of chromosome healing and interstitial telomeres in 40 cases of constitutional abnormalities. Cytogenet Genome Res 125:176–185

    Article  PubMed  CAS  Google Scholar 

  • Fritz B, Dietze I, Wandall A et al (2001) A supernumerary marker chromosome with a neocentromere derived from 5p14–>pter. J Med Genet 38:559–565

    Article  PubMed  CAS  Google Scholar 

  • García-Cruz D, Vásquez AI, Perez-Rulfo D et al (2000) Ring-20-syndrome and loss of telomeric regions. Ann Genet 43:113–116

    Article  PubMed  Google Scholar 

  • Gebhart E (2008) Ring chromosomes in human neoplasias. Cytogenet Genome Res 121:149–173

    Article  PubMed  CAS  Google Scholar 

  • Grimbacher B, Dutra AS, Holland SM et al (1999) Analphoid marker chromosome in a patient with hyper-IgE syndrome, autism, and mild mental retardation. Genet Med 1:213–218

    Article  PubMed  CAS  Google Scholar 

  • Guilherme RS, Bragagnolo S, Pellegrino R et al (2011a) Clinical, cytogenetic and molecular study in a case of r(3) with 3p deletion and review of the literature. Cytogenet Genome Res 134:325–330

    Article  PubMed  Google Scholar 

  • Guilherme RS, Meloni VF, Kim CA et al (2011b) Mechanisms of ring chromosome formation, ring instability and clinical consequences. BMC Med Genet 12:171

    Article  PubMed  Google Scholar 

  • Hamid AB, Kreskowski K, Weise A et al (2012) How to narrow down chromosomal breakpoints in small and large derivative chromosomes—a new probe set. J Appl Genet 53:259–269

    Article  PubMed  CAS  Google Scholar 

  • Herry A, Morel F, Le Bris MJ et al (2004) Molecular cytogenetic characterization of two small chromosome 8 derived supernumerary mosaic markers. Am J Med Genet A 128A:33–38

    Article  PubMed  CAS  Google Scholar 

  • Hou JW, Wang TR (1997) Primed in situ (PRINS) labeling for rapid detection of numeric and structural chromosome anomalies. J Formos Med Assoc 96:46–50

    PubMed  CAS  Google Scholar 

  • Hou JW, Liu CH, Wang TR et al (1992) Mosaic ring chromosome 13 analyzed by fluorescence in situ hybridization: report of a case. J Formos Med Assoc 91:1108–1111

    PubMed  CAS  Google Scholar 

  • Kim JH, Oh PS, Na HY, Kim SH, Cho HC (2009) A case of mosaic ring chromosome 4 with subtelomeric 4p deletion. Korean J Lab Med 29:77–81, Korean

    Article  PubMed  CAS  Google Scholar 

  • Kosztolányi G (1987) Does “ring syndrome” exist? An analysis of 207 case reports on patients with a ring autosome. Hum Genet 75:174–179

    Article  PubMed  Google Scholar 

  • Knegt AC, Li S, Engelen JJ, Bijlsma EK, Warburton PE (2003) Prenatal diagnosis of a karyotypically normal pregnancy in a mother with a supernumerary neocentric 13q21–>13q22 chromosome and balancing reciprocal deletion. Prenat Diagn 23:215–220

    Article  PubMed  CAS  Google Scholar 

  • Knijnenburg J, van Haeringen A, Hansson KB et al (2007) Ring chromosome formation as a novel escape mechanism in patients with inverted duplication and terminal deletion. Eur J Hum Genet 15:548–555

    Article  PubMed  CAS  Google Scholar 

  • Laleye A, Alao MJ, Adjagba M et al (2006) Wolf Hirshhorn syndrome in a case of ring chromosome 4: phenotype and molecular cytogenetic findings. Genet Couns 17:35–40

    PubMed  CAS  Google Scholar 

  • Le Caignec C, Boceno M, Jacquemont S, Nguyen The Tich S, Rival JM, David A (2004) Inherited ring chromosome 8 without loss of subtelomeric sequences. Ann Genet 47:289–296

    Article  PubMed  Google Scholar 

  • Liehr T (2009) Small supernumerary marker chromosomes (sSMCs): a spotlight on some nomenclature problems. J Histochem Cytochem 57:991–993

    Article  PubMed  CAS  Google Scholar 

  • Liehr T (2012) Small supernumerary marker chromosomes. Available from http://www.fish.uniklinikum-jena.de/sSMC.html. Accessed 15 June 2012

  • Liehr T, Pfeiffer RA, Trautmann U (1992) Typical and partial cat eye syndrome: identification of the marker chromosome by FISH. Clin Genet 42:91–96

    Article  PubMed  CAS  Google Scholar 

  • Liehr T, Claussen U, Starke H (2004) Small supernumerary marker chromosomes (sSMC) in humans. Cytogenet Genome Res 107:55–67

    Article  PubMed  CAS  Google Scholar 

  • Liehr T, Mrasek K, Weise A et al (2006a) Small supernumerary marker chromosomes—progress towards a genotype–phenotype correlation. Cytogenet Genome Res 112:23–34

    Article  PubMed  CAS  Google Scholar 

  • Liehr T, Starke H, Senger G, Melotte C, Weise A, Vermeesch JR (2006b) Overrepresentation of small supernumerary marker chromosomes (sSMC) from chromosome 6 origin in cases with multiple sSMC. Am J Med Genet A 140:46–51

    PubMed  Google Scholar 

  • Liehr T, Karamysheva T, Merkas M et al (2010) Somatic mosaicism in cases with small supernumerary marker chromosomes. Curr Genomics 11:432–439

    Article  PubMed  CAS  Google Scholar 

  • Martinez P, Thanasoula M, Carlos AR et al (2010) Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites. Nat Cell Biol 12:768–780

    Article  PubMed  CAS  Google Scholar 

  • Petit P, Fryns JP (1997) Interstitial deletion 2p accompanied by marker chromosome formation of the deleted segment resulting in a stable acentric marker chromosome. Genet Couns 8:341–343

    PubMed  CAS  Google Scholar 

  • Reddy KS, Wang S, Groh S, Gonatos J (2003) SKY assessment of two karyotypes with 0–6 supernumerary marker/ring chromosomes and review of previously reported cases with two or more markers. Am J Med Genet A 118A:156–171

    Article  PubMed  Google Scholar 

  • Rossi E, Riegel M, Messa J et al (2008a) Duplications in addition to terminal deletions are present in a proportion of ring chromosomes: clues to the mechanisms of formation. J Med Genet 45:147–154

    Article  PubMed  CAS  Google Scholar 

  • Rossi E, Messa J, Zuffardi O (2008b) Ring syndrome: still true? J Med Genet 45:766–768

    Article  PubMed  CAS  Google Scholar 

  • Sodré CP, Guilherme RS, Meloni VF et al (2010) Ring chromosome instability evaluation in six patients with autosomal rings. Genet Mol Res 9:134–143

    Article  PubMed  Google Scholar 

  • Starke H, Nietzel A, Weise A et al (2003) Small supernumerary marker chromosomes (SMCs): genotype–phenotype correlation and classification. Hum Genet 114:51–67

    Article  PubMed  CAS  Google Scholar 

  • Sung PL, Chang SP, Wen KC et al (2009) Small supernumerary marker chromosome originating from chromosome 10 associated with an apparently normal phenotype. Am J Med Genet A 149A:2768–2774

    Article  PubMed  Google Scholar 

  • Trifonov V, Fluri S, Binkert F et al (2008) Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated entity? Mol Cytogenet 1:6

    Article  PubMed  Google Scholar 

  • Vera E, Blasco MA (2012) Beyond average: potential for measurement of short telomeres. Aging (Albany NY) 4:379–392

    CAS  Google Scholar 

  • Vermeesch JR, Petit P, Dutra A, Schröck E, Ried T, Fryns JP (1999) A mosaic extra ring chromosome 4 in a female patient with postnatal overgrowth. Genet Couns 10:195–196

    PubMed  CAS  Google Scholar 

  • Vermeesch JR, Baten E, Fryns JP, Devriendt K (2002) Ring syndrome caused by ring chromosome 7 without loss of subtelomeric sequences. Clin Genet 62:415–477

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study is supported in part by the Else Kröner-Fresenius-Stiftung (2011_A42), CAPES (grant to R.S.G #2333-11-2), FAPESP (grant to M.I.M. #50737-1), and DAAD. The cases were provided from Germany by Dr. Viethen, Berchdesgaden; Dr. Kunz, Berlin; Dr. Bartz, Düsseldorf; Dr. Morlot, Düsseldorf; Dr. Pfeiffer, Erlangen; Dr. Albrecht and Dr. Küchler, Essen; Dr. Leipoldt, Freiburg; Dr. Zoll and Dr. Bartels, Göttingen; Dr. Schulze, Hannover; Dr. Henn, Homburg; Dr. Gillessen-Kaesbach, Lübeck; Dr. Ovens-Räder, München; Dr. Mehnert, Neu-Ulm; Dr. Krüger, Rostock; Dr. Kistner, Schwerin; Dr. Dufke, Tübingen; Armenia by Dr. Mkrtchyan, Yerevan; Belgium by Dr. Vermeesch, Leuven; Greece by Dr. Petersen and Dr. Manolakis, Athens; Portugal by Dr. Castedo, Porto; Dr. Marques, Coimbra; Switzerland by Dr. Binkert, Düdingen; and UK by Dr. MacDemont, London. We thank Dr. Marcelo Cioffi de Bello (Sao Carlos, Brazil) for proof reading of the final paper.

Author information

Authors and Affiliations

  1. Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Kollegiengasse 10, 07743, Jena, Germany

    Roberta Santos Guilherme, Elisabeth Klein, Claudia Venner, Ahmed B. Hamid, Samarth Bhatt, Nadezda Kosyakova & Thomas Liehr

  2. Department of Morphology and Genetics, Universidade Federal de São Paulo, Rua Botucatu 740, 04023-900, São Paulo, SP, Brazil

    Roberta Santos Guilherme & Maria Isabel Melaragno

  3. Institut für Humangenetik, Otto-von-Guericke-Universität Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany

    Marianne Volleth

  4. National Medical Center, ‘Mother and Child’, Orlovskaya Str. 66, 220053, Minsk, Belarus

    Anna Polityko & Anna Kulpanovich

  5. Institut für Humangenetik, Postfach, 07740, Jena, Germany

    Thomas Liehr

Authors
  1. Roberta Santos Guilherme
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elisabeth Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claudia Venner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmed B. Hamid
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Samarth Bhatt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria Isabel Melaragno
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marianne Volleth
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anna Polityko
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Anna Kulpanovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nadezda Kosyakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Thomas Liehr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Liehr.

Additional information

Responsible Editor: Fengtang Yang

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. S1

Results of subcentromere-specific multicolor (subcenM)-FISH in four further centric minute-shaped sSMC cases (Sm-4, Sm-5, Sm-6, and Sm-8) gave only signal pattern like that shown schematically in Fig. 1 for this kind of derivative chromosomes. In any of the centric minute-shaped sSMC cases, patterns like in ring-shaped sSMC were seen. Also, the results of subcenM-FISH for two neocentric sSMC cases (Sn-1 and Sn-2) are shown in the lower part of this figure. No centromeric sequences were present in the latter two cases, as further substantiated by microdissection and reverse FISH (results not shown). Scale bars are equal to 2.5 μm. (JPEG 28 kb)

High-resolution image (TIFF 290 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guilherme, R.S., Klein, E., Venner, C. et al. Human ring chromosomes and small supernumerary marker chromosomes—do they have telomeres?. Chromosome Res 20, 825–835 (2012). https://doi.org/10.1007/s10577-012-9316-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10577-012-9316-x

Keywords

Search

Navigation