Human Genetics

, Volume 97, Issue 2, pp 218–223 | Cite as

Trisomy of human chromosome 18: Molecular studies on parental origin and cell stage of nondisjunction

  • Thomas Eggermann
  • Markus M. Nöthen
  • Bernd Eiben
  • Dieter Hofmann
  • Klaus Hinkel
  • Rolf Fimmers
  • Gesa Schwanitz
Original Investigation


We investigated the parent and cell division of origin of the extra chromosome 18 in 62 aneuploids with a free trisomy 18 by using chromosome-18-specific pericentromeric short-sequence repeats. In 46 cases, DNA of patients was recovered from archival specimens, such as paraffin-embedded tissues and fixed chromosomal spreads. In 56 families, the supernumerary chromosome was maternal in origin; in six families, it was paternal. Among the 56 maternally derived aneuploids, we could exclude a postzygotic mitotic error in 52 cases. Among those in which the nondisjunction was attributable to an error at meiosis, 11 were the result of a meiosis I nondisjunction and 17 were caused by a meiosis II error. This result differs markedly from findings in acrocentric chromosomes where nondisjunction at maternal meiosis I predominates. Among the six paternally derived cases, two originated from a meiotic error, indicating that a nondisjunction in paternal meiosis is not as rare as previously suggested.


Internal Medicine Cell Division Metabolic Disease Molecular Study Human Chromosome 
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  1. Antonarakis SE and the Down syndrome collaborative group (1991) Parental origin of the extra chromosome in trisomy 21 as indicated by analysis of DNA polymorphisms. N Engl J Med 324:872–876Google Scholar
  2. Antonarakis SE, Petersen MB, McInnis MG, Adelsberger PA, Schinzel AA, Binkert F, Pangalos C, Raoul O, Slaugenhaupt SA, Hafez M, Cohen MM, Roulson D, Schwartz S, Mikkelsen M, Tranebjaerg L, Greenberg F, Hoar DI, Rudd NL, Warren AC, Metaxotou C, Bartsocas C, Chakravarti A (1992) The meiotic stage of nondisjunction in trisomy 21: determination by using DNA polymorphisms. Am J Hum Genet 50:544–550Google Scholar
  3. Antonarakis SE, Avramopoulos D, Blouin J-L, Talbot CC Jr, Schinzel AA (1993) Mitotic errors in somatic cells cause trisomy 21 in about 4.5% of cases and are not associated with advanced maternal age. Nature Genet 3:146–150Google Scholar
  4. Babu A, Verma RS (1986) The heteromorphic marker on chromosome 18 using restriction endonucleaseAluI. Am J Hum Genet 38:549–554Google Scholar
  5. Bugge M, Petersen M, Hertz J, Mikkelsen M (1994) DNA studies in trisomy 18. Cytogenet Cell Genet 65:141–165Google Scholar
  6. Eggermann T, Nöthen MM, Propping P, Schwanitz G (1993) Molecular diagnosis of trisomy 18 using DNA recovered from paraffin embedded tissues and possible implications for genetic counselling. Ann Génét (Paris) 36:214–216Google Scholar
  7. Fisher JM, Harvey JF, Morton NE, Jacobs PA (1995) Trisomy 18: studies of parent and cell division of origin and the effect of aberrant recombination on nondisjunction. Am J Hum Genet 56:669–675Google Scholar
  8. Guay-Woodford LM, Muecher G, Hopkins SD, Avner ED, Germino GG, Guillot AP, Herrin J, Hollemann R, Irons DA, Primack W, Thomson PD, Waldo FB, Lunt PW, Zerres K (1995) The severe perinatal form of autosomal recessive polycystic kidney disease (ARPKD) maps to chromosome 6p21.1-p12: implications for genetic counseling. Am J Hum Genet 56:1101–1107Google Scholar
  9. Gyapay G, Morissette J, Vignal A, Dib C, Fizames C, Millasseau P, Marc S, Bernardi G, Lathrop M, Weissenbach J (1994) The 1993-94 Généthon human genetic linkage map. Nature Genet 7:246–339Google Scholar
  10. Hassold T, Chin D (1985) Maternal age-specific rates of numerical chromosomal abnormalities with special reference to trisomy. Hum Genet 70:11–17Google Scholar
  11. Hassold T, Jacobs PA (1984) Trisomy in man. Annu Rev Genet 18:69–97Google Scholar
  12. Hassold T, Jacobs PA, Leppert M, Sheldon M (1987) Cytogenetic and molecular studies of trisomy 13. J Med Genet 24:725–732Google Scholar
  13. Hassold TJ, Pettay D, Freeman SB, Grantham M, Takaesu N (1991) Molecular studies of non-disjunction in trisomy 16. J Med Genet 28:159–162Google Scholar
  14. Jonveaux P (1991) PCR amplification of specific DNA sequences from routinely fixed chromosomal spreads. Nucleic Acids Res 19:1946Google Scholar
  15. Kessel AG van, Straub RE, Silverman GA, Gerken S, Overhauser J (1994) Report of the second international workshop on human chromosome 18 mapping. Cytogenet Cell Genet 65:142–163Google Scholar
  16. Kondoh T, Tonoki H, Matsumoto T, Tsukahara M, Niikawa N (1988) Origin of the extra chromosome in trisomy 18. Hum Genet 79:377–378Google Scholar
  17. Kupke KG, Müller U (1989) Parental origin of the extra chromosome in trisomy 18. Am J Hum Genet 45:599–605Google Scholar
  18. MacDonald M, Hassold T, Harvey J, Wang LH, Morton NE, Jacobs P (1994) The origin of 47,XXY and 47,XXX aneuploidy: heterogenous mechanisms and role of aberrant recombination. Hum Mol Genet 3:1365–1371Google Scholar
  19. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215Google Scholar
  20. Nöthen MM, Eggermann T, Erdmann J, Eiben B, Hofmann D, Propping P, Schwanitz G (1993) Retrospective study on the parental origin of the extra chromosome in trisomy 18 (Edwards syndrome). Hum Genet 92:347–349Google Scholar
  21. Petersen MB, Antonarakis SE, Hassold TJ, Freeman SB, Sherman SL, Avramopoulos D, Mikkelsen M (1993) Paternal nondisjunction in trisomy 21: excess of male patients. Hum Mol Genet 2:1691–1695Google Scholar
  22. Sherman SL, Petersen MB, Freeman SB, Hersey J, Pettay D, Taft L, Frantzen M, Mikkelsen M, Hassold TJ (1994) Non-disjunction of chromosome 21 in maternal meiosis I: evidence for a maternal age-dependent mechanism involving reduced recombination. Hum Mol Genet 3:1529–1535Google Scholar
  23. Telenius H, Pelmear AH, Tunnacliffe A, Carter NP, Behmel A, Ferguson-Smith MA, Nordenskjöld M, Pfragner R, Ponder BAJ (1992a) Cytogenetic analysis by chromosome painting using DOP-PCR amplified flow-sorted chromosomes. Genes Chromosom Cancer 4:257–263Google Scholar
  24. Telenius H, Carter NP, Bebb CE, Nordenskjöld M, Ponder BAJ, Tunnacliffe A (1992b) Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics 13:718–725Google Scholar
  25. Ya-gang X, Robinson WP, Spiegel R, Binkert F, Ruefenacht U, Schinzel AA (1993) Parental origin of the supernumerary chromosome in trisomy 18. Clin Genet 44:57–61Google Scholar
  26. Zaragoza MV, Jacobs PA, James RS, Rogan P, Sherman S, Hassold T (1994) Nondisjunction of human acrocentric chromosomes: studies of 432 trisomic fetuses and liveboms. Hum Genet 94:411–417Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Thomas Eggermann
    • 1
  • Markus M. Nöthen
    • 1
  • Bernd Eiben
    • 2
  • Dieter Hofmann
    • 3
  • Klaus Hinkel
    • 4
  • Rolf Fimmers
    • 5
  • Gesa Schwanitz
    • 1
  1. 1.Institut für Humangenetik der Universität BonnBonnGermany
  2. 2.Evangelisches Krankenhaus OberhausenOberhausenGermany
  3. 3.Institut für Kinderpathologie der Universität BonnBonnGermany
  4. 4.Institut für Klinische Genetik des Klinikums Carl-Gustav-Carus der Technischen Universität DresdenDresdenGermany
  5. 5.Institut für Medizinische StatistikDokumentation und Datenverarbeitung der Universität BonnBonnGermany

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