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Sequence of centromere separation another mechanism for the origin of nondisjunction

Summary

The most commonly accepted view about the origin of aneuploidy is that it is due to errors in meiotic division. However, its rare occurrence makes it difficult to explain recurrent births of trisomic children to some parents. This problem causes more serious concern when one accepts that an abnormal (n+1 or n-1) sperm would enter fertilization by overriding thousands, or even millions, of normal haploid sperms. Also, the failure of aneuploidy to be induced in the offspring of mammals treated with mutagens raises questions about the effectiveness of the accepted mode of origin of errors. Current concepts also do not explain why one observes more errors of meiotic I, than of meiotic II, origin. It is known that most chromosomes separating at meta-anaphase junction in mitosis follow a nonrandom, genetically controlled sequence of separation. The present proposal makes use of out-of-phase separation of a rare chromosome, like premature separation in mitosis of the X in elderly humans or of an 18 in parents of trisomy 18 children. The suggestion is made that such out-of-phase separation results in aneuploid cell lines by total failure of the centromere to separate or by it separating too early, before the spindle is formed. The prematurely separating centromeres, it appears, do not attach to spindle fibers and hence cause nondisjunction. Such nondisjunction in embryonic stages will produce apparently normal individuals with mosaicism in somatic and/or gametic tissue. An individual carrying mosaicism in gonadal tissue will produce a large number of abnormal gametes, one of which may have a reasonable chance of entering fertilization. This mode of origin of aneuploidy takes care of all questions raised above and finds support in the data available in the literature. Several of the suggestions made in the hypothesis are easily testable.

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References

  1. Alfi O, Chang R, Azen SP (1980) Evidence for genetic control of nondisjunction in man. Am J Hum Genet 32:477–483

  2. Bajnoczky K, Meggyessy V, Méhes K (1980) Cytogenetic investigation in prednisolone-treated infants. Acta Paediatr Acad Sci Hungarieae 21:139–143

  3. Belcheva RG, Konstantinov GH, Ilyeva HL (1980) Sequence of centromere separation in the mitotic chromosomes in Rana Ridibuda Pall. (Amphibia, Anura). CR Acad Bulg Sci 33:1689–1692

  4. Chandley AC (1982) The origin of aneuploidy. Human Genetics (Part B) Medical Aspects. In: Progr Clinic Biol Res 103 B: 337–347 (ed B. Bonné-Tamir) Alan R. Liss, Inc., New York

  5. Denniston C (1982) Low level radiation and genetic risk estimation in man. Ann Rev Genet 16:239–355

  6. Dewald GW, Boros SJ, Conroy MM, Dahl RJ, Spurbeck JL, Vitek HA (1979) A tdic(5;15)(p13;p11) chromosome showing variation for syndrome. Cytogenetics 24:15–26

  7. Farook SF, Vig BK (1980) Sequence of centromere separation: analysis of mitotic chromosomes of Crepis capillaris and Haplopappus gracilis. Biolog Zentb 99:675–685

  8. Fitzgerald PH, McEwan CM (1977) Total aneuploidy and age-related sex chromosome aneuploidy in cultured lymphocytes of normal men and women. Hum Genet 39:329–337

  9. Fitzgerald PH, Pickering AF, Mercer JM, Miethke PM (1975) Premature centromere division: a mechanism of non-disjunction causing X chromosome aneuploidy in somatic cells of men. Ann Hum Genet 38:417–428

  10. Galloway SM, Buckton KE (1978) Aneuploidy and aging: chromosome studies on a random sample of the population using C-banding. Cytogenet Cell Genet 70:78–95

  11. Hecht F (1982) Unexpected encounters in cytogenetics: repeated abortions and parental sex chromosome mosaicism may indicate risk of nondisjunction. Am J Hum Genet 34:514–515

  12. Lau YF, Hsu TC (1977) Variable modes of Robertsonian fusions. cytogenet Cell Genet 19:231–235

  13. Méhes K (1975) Non-random anaphase segregation of mitotic chromosomes. Acta Genet Med Gemellol 24:175

  14. Méhes K (1978) Non-random centromere division: a mechanism of non-disjunction causing aneuploidy. Hum Hered 28:255–260

  15. Miklos GLG, John B (1979) Heterochromatin and satellite DNA in man: properties and prospects. Am J Hum Genet 31:264–280

  16. Murata M, Vig BK (1980) Sequence of centromere separation: analysis of mitotic chromosomes in a reconstructed karyotype of Vicia faba. L. Biolog Zentb 99:686–693

  17. Prodescue V, Christodorescu D, Tautu C, Cnovirnache M, Constantinescue E (1969) Repeated abortions in XO/XX mosaicism. Lancet 2:217

  18. Reider CL (1982) The formation, structure and composition of mammalian kinetochore and kinetochore fiber. Intern Rev Cytol 79: 1–58

  19. Russell LB, Montgomery CS (1974) The incidence of sex chromosome anomalies following irradiation of mouse spermatogonia with single or fractionated doses of X-rays. Mutat Res 25:367–376

  20. Sankaranarayanan K (1979) The role of non-disjunction in manan an overview. Mutat Res 61:1–28

  21. Singh JR, Miltenburger HG (1977) The effect of cyclophosphamide on the centromere separation sequence in Chinese hamster spermatogonia. Hum Genet 29:359–362

  22. Sinha AK, Pathak S, Nora JJ (1976) Fusion of two apparently intact human X chromosomes. Hum Genet 32:295–300

  23. Therman E, Sarto GE, Patau K (1974) Apparently isodicentric but functionally monocentric X chromosome in man. Am J Hum Genet 26:83–92

  24. Vig BK (1981a) Sequence of centromere separation: analysis of mitotic chromosomes in man. Hum Genet 57:247–252

  25. Vig BK (1981b) Sequence of centromere separation: an analysis of mitotic chromosomes from long-term cultures of Potorus cells. Cytogenet Cell Genet 31:129–136

  26. Vig BK (1982) Sequence of centromere separation: role of centromeric heterochromatin. Genetics 102:785–795

  27. Vig BK (1983) Sequence of centromere separation: Occurrence, possible significance and control. Cancer Genet Cytogenet 8:249–273

  28. Vig BK, Miltenburger HG (1976) Sequence of centromere separation of mitotic chromosomes in Chinese hamster. Chromosoma 5: 75–80

  29. Vig BK, Wodnicki J (1974) Separation of sister centromeres in some chromosomes from cultured human leukocytes. J Hered 65: 149–152

  30. Vig BK, Zinkowsky RP (unpublished) Lateral asymmetry and constitutive heterochromatin in mouse L-cells

  31. Wegner H, Pawlowitzki IH (1981) Quantification of C-band polymorphism by centromeric elevations (Ce-bands). Hum Genet 58: 320–305

  32. Ying KL, Ives EJ (1977) Mitotic behavior of human dicentric Y chromosome. Cytogenet 10:208–218

  33. Zheng H-Z, Burkholder GD (1982) Differential silver staining of chromatin in metaphase chromosomes. Exp Cell Res 141:117–125

  34. Zuffardi O, Damizino C, Poloni L, Pavisi F, Bianchi C, Gergantini L (1980) Ring chromosome 12 and latent centromeres. Cytogenet Cell Genet 28:151–157

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Vig, B.K. Sequence of centromere separation another mechanism for the origin of nondisjunction. Hum Genet 66, 239–243 (1984). https://doi.org/10.1007/BF00286609

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Keywords

  • Elderly Human
  • Rare Occurrence
  • Embryonic Stage
  • Meiotic Division
  • Total Failure