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Chromosome Research

, 14:527 | Cite as

Sporadic aneuploidy in PHA-stimulated lymphocytes of Turner’s syndrome patients

  • Orit Reish
  • Nirit Brosh
  • Rima Gobazov
  • Malka Rosenblat
  • Vitalia Libman
  • Maya Mashevich
Article

Abstract

In line with the view that aneuploidy destabilizes the karyotype, initiating an autocatalytic process that gives rise to further loss and/or gain of chromosomes, we examined whether a constitutional aneuploidy such as monosomy for one chromosome is associated with sporadic loss and/or gain of other chromosomes. We used PHA-stimulated lymphocytes from eight women with Turner's syndrome (six displayed X chromosome monosomy ranging from 60.2% to 97.9%, and two were below 10%), and eight healthy women who served as a control group. Fluorescence in-situ hybridization (FISH), applied at interphase, was used to evaluate the level of aneuploidy for three randomly selected chromosomes (autosomes 8, 15 and 18) in each sample. For each tested chromosome, our results showed a significantly higher level of aneuploid cells in the samples from patients than in those from controls (p < 0.01). The mean level of aneuploid cells for all three tested autosomes was almost twice as high in the patient samples as in the control samples (p < 0.002). It is noteworthy that, in the Turner's syndrome patients, X chromosome disomic cells also displayed increased levels of aneuploidy. It is possible that monosomy of X chromosome in female cells destabilizes their own genome and also affects X disomic cells in the region. One may also speculate that a common factor(s) is involved with both constitutional and sporadic aneuploidy.

Key words

autosomal aneuploidy fluorescence in-situ hybridization mosaicism Turner’s syndrome 

References

  1. Amiel A, Avivi L, Gaber E, Fejgin MD (1998) Asynchronous replication of allelic loci in Down syndrome. Eur J Hum Genet 6: 359–364.PubMedCrossRefGoogle Scholar
  2. Amiel A, Korenstein A, Gaber E, Avivi L (1999) Asynchronous replication of alleles in genomes carrying an extra autosome. Eur J Hum Genet 7: 223–230.PubMedCrossRefGoogle Scholar
  3. Antonarakis SE, Lyle R, Dermitzakis ET, Rymond A, Deutsch S (2004) Chromosome 21 and Down syndrome: from genomics to pathophysiology. Nat Rev Genet 5: 725–738.PubMedCrossRefGoogle Scholar
  4. Bean CJ, Hunt PA, Millie EA, Hassold TJ (2001) Analysis of malsegregating mouse Y chromosome: evidence that the earliest cleavage divisions of the mammalian embryo are non-disjunction prone. Hum Mol Genet 10: 963–972.PubMedCrossRefGoogle Scholar
  5. Blatt J, Olshan AF, Lee PA, Ross JL (1997) Neuroblastoma and related tumors in Turner’s syndrome. J Pediatr 131: 666–670.PubMedCrossRefGoogle Scholar
  6. Carrel L, Willard HF (2005) X-Inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434: 400–404.PubMedCrossRefGoogle Scholar
  7. Carrel L, Cottle AA, Goglin KC Willard HF (1999) A first-generation X-inactivation profile of the human X chromosome. Proc Natl Acad Sci USA 96: 14440–14444.PubMedCrossRefGoogle Scholar
  8. DeBrasi D, Genardi M, D’Agostino A et al. (1995) Double autosomal/gonosomal mosaic aneuploidy: study of nondisjunction in two cases with trisomy 8. Hum Genet 95: 519–525.PubMedCrossRefGoogle Scholar
  9. Dobie KW, Hari KL, Maggert KA, Karpen GH (1999) Centromere proteins and chromosome inheritance: a complex affair. Curr Opin Genet Dev 9: 206–217.PubMedCrossRefGoogle Scholar
  10. Duesberg P, Li R (2003) Multistep carcinogenesis – a chain reaction of aneuploidization. Cell Cycle 2: 202–210.PubMedGoogle Scholar
  11. Duesberg P, Rasnick D (2000) Aneuploidy, the somatic mutation that makes cancer a species of its own. Cell Motil Cytoskelet 47: 81–107.CrossRefGoogle Scholar
  12. Eastmond DA, Pinkel D (1990) Detection of aneuploidy and aneuploidy-inducing agents in human lymphocytes using fluorescence in situ hybridization with chromosome-specific probes. Mutat Res 234: 303–318.PubMedGoogle Scholar
  13. Gravholt CH, Juul S, Naeraa RW, Hansen J (1998) Morbidity in Turner syndrome. J Clin Epidemiol 51: 147–158.PubMedCrossRefGoogle Scholar
  14. Harada N, Abe K, Nishimura T et al. (1998) Origin and mechanism of formation of 45,X/47,XX,+21 mosaicism in a fetus. Am J Med Genet 75: 432–437.PubMedCrossRefGoogle Scholar
  15. Hasle H, Olsen JH, Nielsen J, Hansen J, Friedrich U, Tommerup N (1996) Occurrence of cancer in women with Turner syndrome. Br J Cancer 73: 1156–1159.PubMedGoogle Scholar
  16. Hassold T, Hunt P (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2: 280–291.PubMedCrossRefGoogle Scholar
  17. Hassold TJ, Pettay D, Robinson A, Uchida I (1992) Molecular studies of prenatal origin and mosaicism in 45,X-conceptuses. Hum Genet 89: 647–652.PubMedCrossRefGoogle Scholar
  18. Jacobs PA (1990) The role of chromosome abnormalities in reproductive failure. Reprod Nutr Dev Suppl 1: 63S–74S.Google Scholar
  19. Jacobs PA, Hassold TJ (1995) The origin of numerical chromosome abnormalities. Adv Genet 33: 101–133.PubMedCrossRefGoogle Scholar
  20. Lorda-Sanchez I, Binkert F, Maechler M, Schinzel A (1992) Molecular study of 45,X conceptuses: correlation with clinical findings. Am J Med Genet 42: 487–490.PubMedCrossRefGoogle Scholar
  21. Mukherjee AB, Thomas S (1997) A longitudinal study of human age-related chromosomal analysis in skin fibroblasts. Exp Cell Res 235: 161–169.PubMedCrossRefGoogle Scholar
  22. Pidoux AL, Allshire RC (2000) Centromeres: getting a grip of chromosome. Curr Opin Cell Biol 12: 308–319.PubMedCrossRefGoogle Scholar
  23. Rasnick D (2002) Aneuoloidy theory explains tumor formation, the absence of immune surveillance, and the failure of chemotherapy. Cancer Genet Cytogenet 136: 66–72.PubMedCrossRefGoogle Scholar
  24. Reish O, Gal R, Gaber E, Sher C, Bistritzer T, Amiel A (2002) Asynchronous replication of biallelically expressed loci: a new phenomenon in Turner syndrome. Genet Med 4: 439–443.PubMedCrossRefGoogle Scholar
  25. Schubert R, Eggermann T, Hofstaetter C, Netzer BV, Knöpfle G, Schwanitz G (2002) Clinical, cytogenetic, and molecular findings in 45,X/47,XX,+18 mosaicism: clinical report and review of the literature. Am J Med Genet 110: 278–282.PubMedCrossRefGoogle Scholar
  26. Shapiro BL (1983) Down syndrome: a disruption of homeostasis. Am J Med Genet 14: 241–269.PubMedCrossRefGoogle Scholar
  27. Shi Q, King RW (2005) Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines. Nature 13: 1038–1042.CrossRefGoogle Scholar
  28. Zinn AR, Page DC, Fisher EMC (1993) Turner syndrome: the case of the missing sex chromosome. Trends Genet 9: 90–97.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • Orit Reish
    • 1
    • 2
  • Nirit Brosh
    • 1
  • Rima Gobazov
    • 1
  • Malka Rosenblat
    • 1
  • Vitalia Libman
    • 1
  • Maya Mashevich
    • 1
  1. 1.Genetics InstituteAssaf Harofeh Medical CenterZerifinIsrael
  2. 2.Department of Pediatrics, Assaf Harofeh Medical Center, Zerifin, and Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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