Skip to main content
SpringerLink
Log in

Cytogenetic and molecular analysis of a de novo tandem duplication of chromosome 21

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Summary

We have characterised by cytogenetic and molecular analysis a de novo tandem duplication of chromosome 21. High resolution chromosome examination of lymphocytes revealed the following karyotype in 90% of the cells: 46,XY,dir dup (21)(pter→q22.300::q11.205 →qter). Of these cells, 10% showed a normal karyotype. Gene dosage of chromosome 21 sequences by a slot blot method indicated that the duplication extends from D21S16 to D21S55. In situ hybridization with probes close to the borders of the duplicated segment confirmed the gene dosage data and gave results consistent with a true tandem duplication of chromosome 21. Pulsed field gel electrophoresis of the patient's DNA showed an abnormal restriction band common to D21S55 and D21S16, confirming that the junction point between the two homologous parts of the tandem chromosome brings these two sequences into proximity. Restriction fragment length polymorphism analysis indicated that the abnormal chromosome was maternal in origin and that the rearrangement of chromosome 21 could not have occurred at a post-zygotic stage of development but resulted from a recombination event during maternal gametogenesis. The possible mechanisms of formation of the abnormal chromosome are discussed, as is the presence of cells with normal chromosomes 21, in the patient.

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

Similar content being viewed by others

References

  • Antonarakis SE, Adelsberger PA, Petersen MB, Binkert F, Schinzel AA (1990a) Analysis of DNA polymorphisms suggests that most de novo dup(21) chromosomes in patients with Down syndrome are isochromosomes and not translocations. Am J Hum Genet 47:968–972.

    Google Scholar 

  • Antonarakis SE, the Down syndrome collaborative group (1991b) Parental origin of the extra chromosome in trisomy 21 as indicated by analysis of polymorphism. N Engl J Med 324:872–876.

    Google Scholar 

  • Blouin JL, Rahmani Z, Chettouh Z, Prieur M, Fermanian J, Poissonnier M, Léonard C, Nicole A, Mattei JF, Sinet PM, Delabar JM (1990) Slot blot method for the quantification of DNA sequences and mapping of chromosome rearrangements: application to chromosome 21. Am J Hum Genet 46:518–526.

    Google Scholar 

  • Boulukos KE, Pognonec P, Begue A, Galibert F, Gesquière JC, Stéhelin D, Ghysdael J (1988) Identification in chickens of an evolutionarily conserved cellular ets-2 gene (c-ets-2) encoding nuclear proteins related to the products of c-ets proto-oncogene. EMBO J 7:697–705.

    Google Scholar 

  • Brahe C, Tassone F, Moscetti A, Millington-Ward A, Bova R, Serra A (1990) Molecular study of parental origin of extra chromosome 21 in regular and de novo translocation trisomies. Am J Med Genet 7 [Suppl]:125–128.

    Google Scholar 

  • Burmeister M, Kim S, Roydon Price E, Lange T de, Tantravahi U, Myers RM, Cox DR (1991) A map of the distal region of the long arm of human chromosome 21 constructed by radiation hybrid mapping and pulsed-field gel electrophoresis. Genomics 9:19–30.

    Google Scholar 

  • Chu ML, Myers JC, Bernard MP, Ding JF, Ramirez F (1982) Cloning and characterisation of five overlapping cDNAs specific for the human proα1 (I) collagen chain. Nucleic Acids Res 10:5925.

    Google Scholar 

  • Cox DR, Burmeister M, Price ER, Kim S, Myers RM (1990) Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. Science 250:245–250.

    CAS  PubMed  Google Scholar 

  • Créau-Goldberg N, Gegonne A, Delabar J, Cochet C, Cabanis MO, Stéhelin D, Turleau C, Grouchy J de (1987) Maternal origin of a de novo balanced t(21q21q) identified by ets-2 polymorphism. Hum Genet 76:396–398.

    Google Scholar 

  • Crété N, Delabar JM, Sinet PM, Créau-Goldberg N (1991a) Accurate evaluation of the size of fragments (from 30 to 4700 Kb) in PFGE analysis. Biotechnique (in press).

  • Crété N, Delabar JM, Sinet PM, Créau-Goldberg N (1991b) Construction of a partial chromosome 21 map: long range map of 1200 kb inside the q22.3 region. Advances in Molecular Genetics. Hüthig, Heidelberg, pp 325–331.

    Google Scholar 

  • Dagna Bricarelli F, Pierluigi M, Grasso M, Strigini P, Perroni L (1990) Origin of extra chromosome 21 in 343 families: cytogenetic and molecular approaches. Am J Med Genet 7 [Suppl]: 129–132.

    Google Scholar 

  • Delabar JM, Chettouh Z, Théophile D, Rahmani Z, Blouin JL, Pangalos C, Léonard C, Gilgenkrantz S, Croquette M, Sinet PM (1991) Mapping of chromosomev 21 markers by molecular analysis of partial trisomies and monosomies 21. (Advances in Molecular Genetics). Hüthig, Heidelberg, pp 317–323.

    Google Scholar 

  • Donis-Keller H, Green P, Helms C, Cartinhour S, Weiffenbach B, Stephens K, Keith TP, Bowden DW, Smith DR, Lander ES, Botstein D, Akots G, Rediker KS, Gravius T, Brown VA, Rising MB, Parker C, Powers JA, Watt DE, Kauffman ER, Bricker A, Phipps P, Müller-Kahle H, Fulton TR, Ng S, Schumm JW, Braman JC, Kowlton RG, Barker DF, Crooks SM, Lincoln SE, Daly MJ, Abrahamson J (1987) A genetic linkage map of the human genome. Cell 51:319–337.

    Google Scholar 

  • Faed M, Robertson J, Brown S, Smail PJ, Muckhart RD (1976) Pure partial trisomy for long arm of chromosome 9. J Med Genet 13:239–242.

    Google Scholar 

  • Gardiner K, Laas W, Patterson D (1986) Fractionation of large mammalian DNA restriction fragments using vertical pulsedfield gradient gel electrophoresis. Somat Cell Mol Genet 12:185–195.

    Google Scholar 

  • Gardiner K, Watkins P, Münke M, Drabkin H, Jones C, Patterson D (1988) Partial physical map of human chromosome 21. Somat Cell Mol Genet 14:623–638.

    Google Scholar 

  • Gardiner K, Horisberger M, Kraus J, Tantravahi U, Korenberg J, Rao V, Reddy S, Patterson D (1990) Analysis of human chromosome 21: correlation of physical and cytogenetic maps: gene and CpG island distributions. EMBO J 9:25–34.

    Google Scholar 

  • Goldgaber D, Lerman MI, McBride OW, Scaffiotti U, Gajdusek DC (1987) Characterization and chromosomal localisation of a cDNA encoding brain amyloid of Alzheimer's disease. Science 235:877–880.

    Google Scholar 

  • Grasso M, Giovannucci Uzielli ML, Pierluigi M, Travellini F, Perroni L, Dagna Bricarelli F (1989) Isochromosome not translocation in trisomy 21q21q. Hum Genet 84:63–65.

    Google Scholar 

  • Grouchy J de, Turleau C, Danis F, Kohout G, Briard ML, the help from Chavin-Colin F, Cabanis MO, Doussau de Bazignan M (1978) Trisomie 13qter par duplication en tandem. Ann Génét (Paris) 21:247–251.

    Google Scholar 

  • Harper ME, Saunders GF (1981) Localisation of single copy DNA sequences on G banding human chromosomes by in situ hybridization. Chromosoma 83:431–439.

    Google Scholar 

  • ISCN (1985) An international system for human cytogenetic nomenclature. Harnden DG, Klinger HP (eds) Published in collaboration with Cytogenet Cell Genet. Karger, Basel.

    Google Scholar 

  • Jackson JF, North III ER, Thomas JG (1976) Clinical diagnosis of Down's syndrome. Clin Genet 9:483–487.

    Google Scholar 

  • Keuren ML van, Watkins PC, Drabkin HA, Jabs EW, Gusella JF, Patterson D (1986) Regional localization of DNA sequences on chromosome 21 using somatic cell hybrids. Am J Hum Genet 38:793–804.

    Google Scholar 

  • Kidd KK, Bowcock AM, Schmidtke J, Track RK, Ricciuti F, Hutchings G, Bale A, Pearson P, Willard HF, with help from Gelernter J, Giuffra L, Kubzdela K (1989) Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms. Cytogenet Cell Genet 51:622–947.

    Google Scholar 

  • Kraus JP, Williamson CL, Firgaira FA, Yang-Feng TL, Münke M, Francke U, Rosenberg LE (1986) Cloning and screening with nanogram amounts of immunopurified mRNAs: cDNA cloning and chromosomal mapping of cystathionine B-synthase and the subunit of propionyl-CoA carboxylase. Proc Natl Acad Sci USA 83:2047–2051.

    Google Scholar 

  • Levanon D, Danciger E, Dafni N, Groner Y (1986) Genomic clones of the human liver-type phosphofructokinase. Biochem Biophys Res Commun 141:374–380.

    Google Scholar 

  • Lieman-Hurwitz J, Dafni N, Lavie V, Groner Y (1982) Human cytoplasmic superoxide dismutase cDNA clone: a probe for studying the molecular bioloay of Down syndrome. Proc Natl Acad Sci USA 79:2808–2811.

    Google Scholar 

  • Lungarotti MS, Falorni A, Calabro A, Passalacqua F, Dallapicoola B (1980) De novo duplication 1q32-q42: variability of phenotypic features in partial 1q trisomics. J Med Genet 17:398–401.

    Google Scholar 

  • Mattei JF, Mattei MG, Ardissone JP, Coignet J, Giraud F (1980) Clinical, enzyme and cytogenetic investigations in three newcases of trisomy 8p. Hum Genet 53:315–321.

    Google Scholar 

  • Mattei MG, Philip N, Passage E, Moisan JP, Mandel JL, Mattei JF (1985) DNA probe localisation at 18q11.3 band by in situ hybridization and identification of a small supernumerary chromosome. Hum Genet 69:268–271.

    Google Scholar 

  • Myers JC, Chu ML, Faro SH, Clark WJ, Prockop DJ, Ramirez F (1981) Cloning a cDNA for the pro-α 2 chain of the human type I collagen. Proc Natl Acad Sci USA 78:3516–3520.

    Google Scholar 

  • Perroni L, Dagna Bricarelli F, Grasso M, Pierluigi M, Baldi M, Pedemonte C, Strigini P (1990) Crossing over and chromosome 21 nondisjunction: a study of 60 families. Am J Med Genet 7 [Suppl]: 141–147.

    Google Scholar 

  • Petersen MB, Slaugenhaupt SA, Lewis JG, Warren AC, Chakravarti A, Antonarakis SE (1991) A genetic linkage map of 7 markers on human chromosome 21. Genomics 9:407–419.

    Google Scholar 

  • Poissonnier M, Saint-Paul B, Dutrillaux B, Chassaigné M, Gruyer P, Blignières-Strouk G de (1976) Trisomie 21 partielle (21q21→21q22.2). Ann Génét (Paris) 19:69–73.

    Google Scholar 

  • Prud'homme JF, Fridlansky F, Le Cunff M, Atger M, Mercier-Bodart C, Pichon MF, Milgrom E (1985) Cloning of a gene expressed in human breast cancer and regulated by estrogen in MCF-7 cells. DNA 4:11–21.

    Google Scholar 

  • Rahmani Z, Blouin JL, Créau-Goldberg N, Watkins PC, Mattei JF, Poissonnier M, Prieur M, Chettouh Z, Nicole A, Aurias A, Sinet PM, Delabar JM (1989) Critical role of the D21S55 region on chromosome 21 in the pathogenesis of Down syndrome. Proc Natl Acad Sci USA 86:5958–5962.

    Google Scholar 

  • Rahmani Z, Blouin JL, Créau-Goldberg N, Watkins PC, Mattei JF, Poissonnier M, Prieur M, Chettouh Z, Nicole A, Aurias A, Sinet PM, Delabar JM (1990) Down syndrome critical region around D21S55 on proximal 21q22.3. Am J Med Genet 7 [Suppl]: 98–103.

    Google Scholar 

  • Sacchi N, Gusella JF, Perroni L, Dagna Bricarelli F, Papas TS (1988) Lack of evidence for association of meiotic nondisjunction with particular DNA haplotypes on chromosome 21. Proc Natl Acad Sci USA 85:4794–4798.

    Google Scholar 

  • Scherer G, Schempp W, Baccichetti C, Lenzini E, Dagna Bricarelli F, Lamba Carbone LD, Wolf U (1989) Duplication of an Xp segment that includes the ZFX locus causes sex inversion in man. Hum Genet 81:291–294.

    Google Scholar 

  • Sinet PM, Couturier J, Dutrillaux B, Poissonnier M, Raoul O, Rethoré MO, Allard D, Lejeune J, Jerome H (1976) Trisomie 21 et superoxyde dismutase-1 (IPOA-A): tentative de localisation sur la sous-bande 21q22.1. Exp Cell Res 9:47–55.

    Google Scholar 

  • Stewart GD, Harris P, Galt J, Ferguson-Smith MA (1985) Cloned DNA probes regionally mapped to human chromosome 21 and their use in determining the origin of nondisjunction. Nucleic Acids Res 13:4125–4132.

    Google Scholar 

  • Stinissen P, Vandenberghe A, Van Broeckhoven C (1990) A high frequency EcoRI RFLP detected at the D21S13 locus. Nucleic Acids Res 18:1319.

    Google Scholar 

  • Takaesu N, Jacobs PA, Cockwell A, Blackston RD, Freeman S, Nuccio J, Kurnit DM, Uchida I, Freeman V, Hassold T (1990) Nondisjunction of chromosome 21. Am J Med Genet 7 [Suppl]:175–181.

    Google Scholar 

  • Tanzi RE, Haines JL, Watkins PC, Stewart GD, Wallace MR, Hallewell R, Wong C, Wexler NS, Conneally PM, Gusella JF (1988) Genetic linkage map of human chromosome 21. Genomics 3:129–136.

    Google Scholar 

  • Turleau C, Grouchy J de, Chavin-Colin F, Roubin M, Brissaud PE, Repessé G, Safar A, Borniche P (1975) Partial trisomy 9p: a new syndrome. Humangenetik 29:233–241.

    Google Scholar 

  • Warren AC, Slaugenhaupt SA, Lewis JG, Chakravarti A, Antonarakis SE (1989) A genetic linkage map of 17 markers on human chromosome 21. Genomics 4:579–591.

    Google Scholar 

  • Watkins PC, Tanzi RE, Gibbons KT, Tricoli JV, Landes G, Eddy R, Shows TB, Gusella JF (1985a) Isolation of polymorphic DNA segments from human chromosome 21. Nucleic Acids Res 13:6075–6088.

    Google Scholar 

  • Watkins PC, Watkins PA, Hoffman N, Stanislovitis P (1985b) Isolation of single-copy probes detecting DNA polymorphisms from a cosmid library of chromosome 21. Cytogenet Cell 40:773–774.

    Google Scholar 

  • Weil D, Mattei MG, Passage E, Van Cong NG, Pribula-Conway D, Mann K, Deutzmann R, Timpl R, Chu ML (1988) Cloning and chromosomal localisation of human genes encoding the three chains of type VI collagen. Am J Hum Genet 42:435–445.

    Google Scholar 

  • Wong C, Kazazian HH Jr. Stellen G, Earnshaw WC, Keuren ML Van Antonarakis SE (1989) Molecular mechanism in the formation of a human ring chromosome 21. Proc Natl Acad Sci USA 86:1914–1918.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. URA 1335 Centre National de la Recherche Scientifique. Laboratoire de Biochimie Génétique, 15, Paris Cedex, France

    Jean-Louis Blouin, Arlette Bruel, Jean-Maurice Delabar & Pierre-Marie Sinet

  2. U173 Institut National de la Santé et de la Recherche Médicale, 15, Paris Cedex, France

    Nicole Créau-Goldberg

  3. Service de Cytogénétique. Hôpital Necker-Enfants Malades, 149, Rue de Sèvres, 15, Paris Cedex, France

    Marguerite Prieur

  4. URA 620 C.N.R.S. Institut Curie, 26. Rue d'Ulm, 05, Paris Cedex, France

    Alain Aurias & Françoise Apiou

  5. U276 I.N.S.E.R.M. Institut Pasteur, 25, Rue du Docteur Roux, 15, Paris Cedex, France

    Catherine Alcaide-Loridan

  6. University of Colorado Health Sciences Center, 4000 East 9th Avenue, 80262, Denver, CO, USA

    Jan Kraus

Authors
  1. Jean-Louis Blouin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alain Aurias
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicole Créau-Goldberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Françoise Apiou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Catherine Alcaide-Loridan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Arlette Bruel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marguerite Prieur
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jan Kraus
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jean-Maurice Delabar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pierre-Marie Sinet
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blouin, JL., Aurias, A., Créau-Goldberg, N. et al. Cytogenetic and molecular analysis of a de novo tandem duplication of chromosome 21. Hum Genet 88, 167–174 (1991). https://doi.org/10.1007/BF00206066

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00206066

Keywords

Search

Navigation