Detection of Chromosomal Aberrations in Interphase and Metaphase Cells in Prenatal and Postnatal Studies

  • William G. Kearnsand
  • Peter L. Pearson
Part of the Methods in Molecular Biology™ book series (MIMB, volume 33)


The identification of numerical and structural chromosome abnormalities by routine and high resolution cytogenetic studies plays an important role in the diagnosis and treatment of various diseases. The analysis of structural aberrations is relatively gross and only permits the visual diagnosis of aberrations of single chromosome bands on the order of about seven million base pairs. Chromosome aberrations involving less than five million or so base pairs or those with indistinct banding patterns are difficult or impossible to detect using routine or high resolution cytogenetic studies. Standard cytogenetic techniques also require that the cells to be analyzed must be actively dividing and that they may be arrested during metaphase, thus requirmg a substantial amount of time for sample preparation and analysis.


Chorionic Villus Metaphase Chromosome Preparation Cytogenetic Diagnosis Maternal Cell Contamination Cosmid Contig 
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. 1.
    Rhoads, G. G, Jackson, L G., Schlesselman, S. E, De la Cruz, F. F, Desnick, R J., Golbus, M S, Ledbetta, D H, Lubs, H A, Mahoney, M J., Pergament, E, Simpson, J L, Carpenter, R. J., Elias, S., Ginsberg, N. A., Goldberg, J D, Hobbins, J C, Lynch, C, Shiono, P. H., Wapner, R. J, and Zachary, J M (1989) The safety and efficacy of chononic villus sampling for early prenatal diagnosis of cytogenetic abnormalities. N. Engl J Med. 320, 609–617PubMedCrossRefGoogle Scholar
  2. 2.
    Robinson, A, Bender, B, and Linden, M (1991) Prognosis of prenatally diagnosed children with sex chromosome abnormalitie Birth Defects 15, 203–241Google Scholar
  3. 3.
    Cremer, T., Landegent, J, Bruckner A, School, H P, Schardin, M, Hager, H D., Devilee, P, Pearson, P, and van der Ploeg, M (1986) Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and nonradioactive in situ hybridization techniques, diagnosis of trisomy 18 with probe L1 84 Hum. Genet 74, 346–352PubMedCrossRefGoogle Scholar
  4. 4.
    Klinger, K. W., Dakowski, W., Leverone, B, Locke, P, Nass, S. G, Lerner, T, and Landes, G (1990) Prenatal detection of aneuploidy of 21,18, 13, X, or Y by interphase in situ hybridization. Am J. Hum. Genet. (Suppl. 47), A224Google Scholar
  5. 5.
    Klinger, K., Landes, G., Shook, D., Harvey, R., Lopez, L, Locke, P, Lerner, T, Osathanondh, R, Leverone, B, Houseal, T., Pavelka, K, and Dackowski, W (1992) Rapid detection of chromosome aneuploidies in uncultured amniocytes by using fluorescence in situ hybridization (FISH) Am. J. Hum Genet 51, 55–65PubMedGoogle Scholar
  6. 6.
    Rosenberg, C, Blakemore, K. J, Kearns, W G, Giraldez, R A, Escallon, C. S., Pearson, P. L., and Stetten, G (1992) Analysis of reciprocal translocation by chromosome painting applications and limitations of the technique. Am. J Hum. Genet 50, 700–705.PubMedGoogle Scholar
  7. 7.
    Rosenberg, C, Stetten, G., Kearns, W G, Littlefield, J W, Thomas, G, and Pearson, P L (1991) Use of DNA libraries and fluorescent m situ hybridization to identify translocations and duplications. Am. J Hum Genet (Suppl.)49, 306Google Scholar
  8. 8.
    Batista, D. A.S, Tuck-Muller, C. M., Martinez, J E, Kearns, W G, Pearson, P L, and Stetten, G. (1993) A complex chromosomal rearrangement detected prenatally and studied by fluorescence in situ hybridization Hum Genet. 92, 117–121.PubMedCrossRefGoogle Scholar
  9. 9.
    Blakemore, K J, Rosenberg, C, Jaswaney, V. L, Pressman, E. K, Kearns, W G., Pearson, P L, and Stetten, G (1993) Rapid diagnosis of trisomy 18 and dizygosity in twins using fluorescence in situ hybridization on uncultured amniocytes J Mat-Fet Med. 2, 197–200Google Scholar
  10. 10.
    Smith, D W (1964) Autosomal abnormalities Am. J. Obstet. Gynecol 90, 1055–1077.PubMedGoogle Scholar
  11. 11.
    Carter, P E., Pearn, J. H., Bell, J, Martin, N, and Anderson, N G (1985) Survival in trisomy 18. Clin. Genet. 27, 59–61.PubMedCrossRefGoogle Scholar
  12. 12.
    Ward, B. E., Gersen, S. L, Carelh, M P, McGuire, N. M., Dackowski, W R., Weinstein, M, Sandlin, C, Warren, R, and Klinger, K W (1993) Rapid prenatal diagnosis of chro-mosomal aneuploidies by fluorescence in situ hybridization, clinical experience with 4500 specimens. Am. J Hum. Genet. 52, 854–865.PubMedGoogle Scholar
  13. 13.
    Rosenberg, C, Blakemore, K J, Kearns, W G, Giraldez, R A., Escallon, C. S, Pearson, P. L., and Stetten, G. (1992) Analysis of reciprocal translations by chromosome painting, applications and limitations of the technique. Am. J Hum. Genet. 50, 700–705PubMedGoogle Scholar
  14. 14.
    Kraker, W. J, Borell, T. J., Schad, C. R, Pennington, M. J., Karnes, P. S., Dewald, G. W, and Jenkins, R B. (1992) Fluorescent in situ hybridization: use of whole chromosome paint probes to identify unbalanced chromosome translocations. Mayo Clin. Proc 67, 658–662.PubMedGoogle Scholar
  15. 15.
    Steinbach, P. and Benz, R. (1983) Demonstration of gene dosage effects for AK3 and GALT in fibroblasts from a fetus with 9p trisomy. Hum. Genet 63, 290,291PubMedGoogle Scholar
  16. 16.
    Ebbin, A., J, Wilson, M G, Towner, J W, and Slaughter, J P. (1973) Prenatal diagnosis of an inherited translocation between chromosomes no. 9 and 18 J Med. Genet. 10, 65–69.PubMedCrossRefGoogle Scholar
  17. 17.
    Melnyk, A, R., Weiss, L, Van Dyke, D L., and Jarvi, P (1981) Malformation syndrome of duplication 12q24 l→qter. Am J. Med. Genet 10, 357–365PubMedCrossRefGoogle Scholar
  18. 18.
    Therman, E and Patau, K (1974) Abnormal X chromosomes in man: origin, behavior and effects. Humangenetik 25, 1–16PubMedGoogle Scholar
  19. 19.
    Tuck-Miller, C M., Martinez, J. E., Batista, D A.S., Kearns, W. G., and Wertelecki, W (1993) Duplication of the short arm of the X chromosome in mother and daughter Hum Genet. 91, 395–400.Google Scholar
  20. 20.
    Pai, G S and Thomas, G. H (1980) A new R-banding technique in clinical cytogenetics Hum. Genet 54, 41–45PubMedCrossRefGoogle Scholar
  21. 21.
    Wilson, M. G., Modebe, O., Towner, J. W., Frasier, S. D., and Lin, M. S. (1983) Ullrich-Turner syndrome associated with interstitial deletion of Xpll 2→p22 31 Am J Med Genet. 14, 567–576.PubMedCrossRefGoogle Scholar
  22. 22.
    Kousseff, B. G, Nichols, P., Essig, Y P., Miller, K, Weiss, A., and Tedesco, T. A. (1987) Complex chromosome rearrangements and congenital anomalies Am J Med Genet. 26, 771–782PubMedCrossRefGoogle Scholar
  23. 23.
    Bass, H N, Sparkes, R. S, Lessner, M. M, Fox, M, Phoenix, B, and Bernar, J. (1985) A family with three independent autosomal translocations associated with 7q32→7qter syndrome J Med Genet. 22, 59–63PubMedCrossRefGoogle Scholar
  24. 24.
    Meer, B., Wolff, G., and Back, E. (1981) Segregation of a complex rearrangement of chromosomes 6, 7, 8, and 12 through three generations. Hum Genet. 58, 221–225PubMedCrossRefGoogle Scholar
  25. 25.
    Kleczkowska, A, Fryns, J. P., and van den Berghe, H (1982) Complex chromosomal rearrangements (CCR) and their genetic consequences. J Genet. Hum. 30, 199–214PubMedGoogle Scholar
  26. 26.
    Walker, A., P. and Bocian, M. (1987) Partial duplication 8ql2→q21 2 in two sibs with maternally derived insertional and reciprocal translocations case reports and review of partial duplications of chromosome 8. Am. J. Med Genet. 27, 3–22PubMedCrossRefGoogle Scholar
  27. 27.
    Gorski, J L, Kistenmacher, M L, Punnett, H H, Zackai, E. H., and Emanuel, B S (1988) Reproductive risks for carriers of complex chromosomal rearrangements analysis of 25 families Am J. Med. Genet 29, 247–261.PubMedCrossRefGoogle Scholar
  28. 28.
    Hook, E. B. and Cross, P. K (1987) Rates of mutant and inherited structural cytogenetic abnormalities detected at amniocentesis. results on about 63,000 fetuses. Ann. Hum Genet 51, 27–55.PubMedCrossRefGoogle Scholar
  29. 29.
    Willey, A. M., Carter, T. P, Kelly, S., and Porter, I H., eds. (1982) Clinical Genetics Problems in Diagnosis and Counseling. Academic, New York, pp 63–75.Google Scholar
  30. 30.
    Warburton, D. (1984) Outcome of cases of de novo structural rearrangements diagnosed at amniocentesis. Prenat Diagn. (Spec. Iss) 4, 69–80CrossRefGoogle Scholar
  31. 31.
    Bogart, M H, Bradshaw, C L, Jones, O W, and Schanberger, J E (1986) Prenatal diagnosis and follow up of a child with a complex chromosome rearrangement J Med Genet. 23, 180–183PubMedCrossRefGoogle Scholar
  32. 32.
    Stoll, C, Flori, E., MacLear, J, and Renaud, R. (1979) Prenatal diagnosis and postnatal follow-up of an abnormal child with two de novo apparently balanced translocations Hum Genet. 47, 221–224PubMedCrossRefGoogle Scholar
  33. 33.
    Kim, H. J., Perle, M A, Bogosian, V., and Greco, A (1986) Prenat. al diagnosis of a de novo complex chromosomal rearrangement involving four chromosomes. Prenat. Diagn. 6, 211–216.PubMedCrossRefGoogle Scholar
  34. 34.
    Batista, D A. S., Tuck-Muller, C. M., Martinez, J. E., Kearns, W. G, Pearson, P. L, and Stetten, G. (1993) A complex chromosomal rearrangement detected prenatally and studied by fluorescence in situ hybridization. Hum. Genet. 92, 117–121PubMedCrossRefGoogle Scholar
  35. 36.
    Mizunoe, T. and Young, S R (1992) Low fluorescence alpha satellite region yields negative result. Prenat. Diagn 12, 549,550PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1994

Authors and Affiliations

  • William G. Kearnsand
    • 1
    • 2
  • Peter L. Pearson
    • 1
  1. 1.Center for Medical GeneticsJohns Hopkins University School of MedicineBaltimore
  2. 2.Center for Pediatric ResearchChildren’s Hospital of the King’s Daughters, Eastern Virginia Medical SchoolNorfolk

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